Prevalence and incidence of rare diseases: Bibilographic data

Number 2 | March 2016

Prevalence and incidence of rare diseases: Bibilographic data Diseases listed by decreasing prevalence, incidence or number of published cases

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Methodology Orphanet carries out a systematic survey of literature in order to estimate the prevalence and incidence of rare diseases. This study aims to collect new data regarding point prevalence, birth prevalence and incidence, and to update already published data according to new scientific studies or other available data. This data is presented in the following reports published biannually: • Prevalence, incidence or number of published cases listed by diseases (in alphabetical order) ; • Diseases listed by decreasing prevalence, incidence or number of published cases ;

Data collection A number of different sources are used :



Registries (RARECARE, EUROCAT, etc) ;



National/international health institutes and agencies (Institut National de Veille Sanitaire (French Institute of Health Surveillance); American Center of Disease Control and Prevention, American National Cancer Institute, European Medicines Agency, World Health Organization etc) ;



Medline is consulted using the following search algorithm : «Disease names» AND Epidemiology[MeSH:NoExp] OR Incidence[Title/abstract] OR Prevalence[Title/ abstract] OR Epidemiology[Title/abstract];



Medical texts, grey literature and reports from experts ;



Orphanet collaborating experts.

Data characteristics The data published in this document are worldwide estimations, or European estimations if a worldwide estimation is not available. The published data is raw collected data or extrapolations of raw data at worldwide or European level when no genetic founder effect is suspected as a cause of a disease.

If a range of national data is available, the average is calculated to estimate the worldwide or European prevalence or incidence. When a range of data sources is available, the most recent data source that meets a certain number of quality criteria is favoured (registries, meta-analyses, population-based studies, large cohorts studies). For congenital diseases, the prevalence is estimated, so that: Prevalence = birth prevalence x (patient life expectancy/general population life expectancy). When only incidence data is documented, the prevalence is estimated when possible, so that : Prevalence = incidence x disease mean duration. When neither prevalence nor incidence data is available, which is the case for very rare diseases, the number of cases or families documented in the medical literature is provided.

Limitations of the study The prevalence and incidence data presented in this report are only estimations and cannot be considered to be absolutely correct. The average values presented in this report do not take into account the heterogeneous nature of the methodologies employed by the studies considered in the literature survey. The validity and exactitude of raw data sources is taken for granted and have not been verified. Thus, confusion between terms such as incidence and prevalence and/or birth prevalence is possible due to the interchangeable use of these terms in certain sources. It is possible that prevalence is overestimated in some cases as epidemiological studies are generally based on hospital data in regions with higher prevalence.

Data presentation Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence.

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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List of diseases or groups of diseases by decreasing prevalence ORPHA Number

Disease or Group of diseases

79457 Maculopapular cutaneous mastocytosis 1480 Ventricular septal defect Fetal and neonatal alloimmune 853 thrombocytopenia 268810 Posterior meningocele 3388 Neural tube defect

Estimated prevalence (/100,000)

450.0 BP* 272.0 BP* 112.5 BP*

ORPHA Number

Disease or Group of diseases

Acute sensorineural hearing loss by acute 90059 acoustic trauma or sudden deafness or surgery induced acoustic trauma Non-papillary transitional cell carcinoma of 209989 the bladder 545 Follicular lymphoma 97230 Solar urticaria

Estimated prevalence (/100,000)

37.0 * 37.0 * 36.0 * 36.0 *

1457

Aorta coarctation

35.6 BP*

2764

Osteochondritis dissecans

35.0 * 35.0 BP*

91.05 BP*

1048 Isolated anencephaly/exencephaly 70475 Radiation proctitis 94059 Uremic pruritus

91349 Non-functioning pituitary adenoma 648 Noonan syndrome

80.025 *

3303

34.0 BP

70.0 BP*

636

182130 Tumor of endocrine glands 2014 Cleft palate

64.0 *

100.0 BP*

53.6 BP*

535

Cutaneous lupus erythematosus

50.0 *

706

Patent arterial duct

50.0 BP*

8

47,XYY syndrome

50.0 BP*

48

Congenital bilateral absence of vas deferens 50.0 *

63259 Iniencephaly Pneumonia caused by Pseudomonas 90066 aeruginosa infection 93100 Renal agenesis, unilateral 67037 Squamous cell carcinoma of head and neck

50.0 *

2185

46.5 BP*

Congenital hydrocephalus Congenital isolated thyroxine-binding 209893 globulin deficiency 275555 Preeclampsia 93108 Renal dysplasia

50.0 * 50.0 BP 49.0 *

46.0 * 45.0 * 43.5 BP*

3375

Trisomy X

42.5 *

801

Scleroderma

42.0

217071 Renal cell carcinoma 363999 Non-immune hydrops fetalis 1646

Partial chromosome Y deletion

42.0 * 42.0 BP 41.65

73247 Eosinophilic esophagitis 768 Familial long QT syndrome

40.08

294 Fetal cytomegalovirus syndrome 98497 Genetic peripheral neuropathy 97292 Cardiogenic shock

40.0 *

101016 Romano-Ward syndrome 3189 Congenital pulmonary valve stenosis

40.0 *

40.0 BP* 40.0 40.0 * 39.3 BP*

Tetralogy of Fallot

35.0 * 35.0 *

Neurofibromatosis type 1 226292 Permanent congenital hypothyroidism 858 Congenital toxoplasmosis

33.3 BP

439167 Placental insufficiency 908 Fragile X syndrome

33.0

70476 Vernal keratoconjunctivitis 90051 Sepsis in premature infants

32.0 *

90058 Spinal cord injury 216675 Transposition of the great arteries

32.0 *

33.3 BP* 33.0 BP* 32.5 32.0 * 31.7 BP*

2140

Congenital diaphragmatic hernia

30.0 BP

563

Peripartum cardiomyopathy

30.0 BP

1330

Partial atrioventricular canal

30.0 *

729 Polycythemia vera 213500 Ovarian cancer 330001 Wild type ATTR amyloidosis

30.0 *

Non-acquired combined pituitary hormone 467 deficiency 411527 Central retinal vein occlusion 1656 Dermatitis herpetiformis

30.0 * 30.0 * 29.0 BP* 28.0 * 27.0 *

67038 B-cell chronic lymphocytic leukemia 791 Retinitis pigmentosa

27.0 *

70568 Posttransplant lymphoproliferative disease 54057 Thrombotic thrombocytopenic purpura

26.2 *

26.7

25.5 * Cytomegalovirus disease in patients with 137698 impaired cell mediated immunity deemed at 25.5 * risk 166 Charcot-Marie-Tooth disease 25.0 * 3002 Immune thrombocytopenic purpura 25.0 * 701

25.0 *

98715 Uveitis 38.0 * 90056 Moderate and severe traumatic brain injury 37.8 * 567 22q11.2 deletion syndrome 37.5 BP

Alopecia universalis Hereditary breast and ovarian cancer 145 syndrome 2073 Narcolepsy-cataplexy 95719 Thyroid hemiagenesis

226295 Primary congenital hypothyroidism

93402 Syndactyly type 1

25.0 BP*

442

Congenital hypothyroidism

38.0 BP*

37.5 *

25.0 * 25.0 * 25.0

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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ORPHA Number

Disease or Group of diseases

94058 Neovascular glaucoma 1199 Esophageal atresia

Estimated prevalence (/100,000)

774

Hereditary hemorrhagic telangiectasia

16.0 *

1201

Atresia of small intestine

16.0 BP*

2368

Gastroschisis

23.7 BP*

3394

Soft tissue sarcoma

23.7 *

2137

Chronic autoimmune hepatitis

23.5

1851

Multicystic dysplastic kidney

23.26 BP

90080 217067 217080 636 95711 186

85410 Oligoarticular juvenile arthritis 60 Alpha-1-antitrypsin deficiency 70 3389

23.2 BP 23.0 * 22.0 * 22.0 * 22.0 * 21.3 * 21.3 * 21.05 20.5 * 20.0 *

Proximal spinal muscular atrophy

20.0 BP*

Tuberculosis

20.0 *

1329

Complete atrioventricular canal

20.0 BP*

557

Isolated anorectal malformation

20.0 BP

130

Brugada syndrome

20.0 *

35122 Congenital sucrase-isomaltase deficiency 1330 Partial atrioventricular canal Arrhythmogenic right ventricular cardiomyopathy 70587 Infant acute respiratory distress syndrome 90062 Acute liver failure 247

90081 AIDS wasting syndrome 261197 Proximal 16p11.2 microdeletion syndrome 823

Isolated spina bifida

20.0 * 20.0 BP*

Primary membranoproliferative 54370 glomerulonephritis 90064 Acute peripheral arterial occlusion 137599 Stromal keratitis

16.0 16.0 * 16.0 * 16.0 * 16.0 *

83463 Microtia 90291 Systemic sclerosis

15.5 BP

98896 Duchenne muscular dystrophy 558 Marfan syndrome

15.1 BP*

15.4 * 15.0

232

Sickle cell anemia

15.0 *

2382

Lennox-Gastaut syndrome

15.0 *

2828 Young-onset Parkinson disease 88673 Hepatocellular carcinoma 94093 Neuroleptic malignant syndrome

15.0 *

221061 Familial cerebral cavernous malformation 163934 Atopic keratoconjunctivitis

15.0

166260 Dentinogenesis imperfecta type 2 49042 Dentinogenesis imperfecta

14.6 *

95712 Thyroid ectopia 214 Cystinuria

14.3 *

101959 Chronic primary adrenal insufficiency 2162 Holoprosencephaly

14.0 *

3193

15.0 * 15.0 * 15.0 * 14.5 * 14.0 13.4 BP*

Supravalvular aortic stenosis 44890 Gastrointestinal stromal tumor 70589 Bronchopulmonary dysplasia

13.3 *

423461 Mucolipidosis type III alpha/beta 100088 Thyroid carcinoma

13.0

13.0 * 13.0 * 12.7

Triploidy

12.6 BP*

273

Steinert myotonic dystrophy

12.5

20.0 *

797

Sarcoidosis

12.5

20.0 *

285

Ehlers-Danlos syndrome, hypermobility type 12.5 *

20.0 *

903

Von Willebrand disease

20.0 * 18.6 BP* 18.5 BP

90061 Non-infectious posterior uveitis 154 Familial isolated dilated cardiomyopathy

18.0 *

18.0 * 17.5 *

65753 Charcot-Marie-Tooth disease type 1 3380 Trisomy 18

17.5

2032

16.7

77240 Primary lymphedema 461 Recessive X-linked ichthyosis

36258 Buerger disease 544 Diffuse large B-cell lymphoma

3376

20.0

30391 Biliary atresia 704 Pemphigus vulgaris

Idiopathic pulmonary fibrosis

Estimated prevalence (/100,000)

24.3 BP*

Craniosynostosis 24.3 BP* Congenitally uncorrected transposition of the 860 24.25 BP* great arteries 2248 Hypoplastic left heart syndrome 24.0 BP 171901 Primary cutaneous T-cell lymphoma 24.0 *

Scarring in glaucoma filtration surgical procedures Pouchitis Pulmonary fungal infections in patients deemed at risk Neurofibromatosis type 1 Congenital hypothyroidism due to developmental anomaly Primary biliary cirrhosis

Disease or Group of diseases

24.4 *

1531

97363 Unilateral multicystic dysplastic kidney 228113 Anal fistula

ORPHA Number

16.7 BP 16.7 * 16.6 *

2415 Lymphatic malformation 85138 Addison disease Medium chain acyl-CoA dehydrogenase 42 deficiency 95426 Chronic pain requiring intraspinal analgesia 29073 Multiple myeloma 660

Omphalocele

1866 Focal, segmental or multifocal dystonia 98878 Hemophilia A 70573 Small cell lung cancer 635

Neuroblastoma

12.5 12.5 * 12.5 * 12.0 BP* 12.0 * 11.9 * 11.7 BP* 11.7 * 11.25 BP 11.2 * 11.0 *

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

3109

Mayer-Rokitansky-Küster-Hauser syndrome 11.0 BP

579

Mucopolysaccharidosis type 1

8.0 *

890

Hepatic veno-occlusive disease

11.0 *

930

Idiopathic achalasia

8.0

11.0 *

3451

West syndrome

8.0 *

10.9 BP*

194

Ocular coloboma

8.0 BP*

85443 AL amyloidosis 388 Hirschsprung disease 904

Williams syndrome

10.8 BP

700

Alopecia totalis

10.5 *

827

Stargardt disease

10.0 *

1146

Digitotalar dysmorphism

10.0

2612

Linear nevus sebaceus syndrome

10.0 BP*

716

Phenylketonuria

10.0 BP*

418

Congenital adrenal hyperplasia

10.0 *

805

Tuberous sclerosis complex

10.0 BP*

654

Nephroblastoma

10.0 BP*

569

Familial or sporadic hemiplegic migraine

10.0 *

233

Duane retraction syndrome

10.0 *

3157

Septo-optic dysplasia spectrum

10.0 BP*

412

Hyperlipoproteinemia type 3 Hypereosinophilic syndrome of 3260 undetermined significance Catecholaminergic polymorphic ventricular 3286 tachycardia 31112 Dermatofibrosarcoma protuberans 64740 Recurrent acute pancreatitis 90065 90076 183422 182067 1114

Acquired aneurysmal subarachnoid hemorrhage Partial deep dermal and full thickness burns Polymalformative genetic syndrome with increased risk of developing cancer Glial tumor Aplasia cutis congenita

10.0 10.0 * 10.0 * 10.0 *

90290 CREST syndrome Juvenile rheumatoid factor-negative 85408 polyarthritis 88991 Congenital heart malformation 589 Myasthenia gravis 448

Hemophilia Sporadic adult-onset ataxia of unknown 247234 etiology 72 Angelman syndrome 666 Osteogenesis imperfecta 2004

Laryngo-tracheo-esophageal cleft

1464

Univentricular heart Classic congenital adrenal hyperplasia due to 315306 21-hydroxylase deficiency, salt wasting form Classic congenital adrenal hyperplasia due to 315306 21-hydroxylase deficiency, salt wasting form 586 Cystic fibrosis 821 Sotos syndrome

7.7 * 7.6 * 7.5 7.5 * 7.5 BP* 7.5 BP 7.5 * 7.5 BP* 7.4 * 7.1 BP 7.1 *

705

Pendred syndrome

7.0 *

10.0 *

1332

7.0 *

10.0 *

90794

10.0 *

90794

Medullary thyroid carcinoma Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Recurrent hepatitis C virus induced liver disease in liver transplant recipients Primary progressive aphasia

10.0 * 10.0 BP

90052

9.29 *

79665 Gardner syndrome Mitochondrial oxidative phosphorylation 2443 disorder due to nuclear DNA anomalies 900 Granulomatosis with polyangiitis 1203 Duodenal atresia

9.1 BP

261236 16p13.11 microdeletion syndrome 2059 Fryns syndrome

1203

Syringomyelia

7.77

10.0 *

95432

3280

7.8 BP*

Polymyositis

9.8

98292 Mastocytosis Congenital total pulmonary venous return 99125 anomaly 137914 Choanal atresia 99981 Apnea of prematurity

8.0 *

732

70482 Carcinoma of esophagus 223727 Bone sarcoma

Duodenal atresia

8.0 *

9.0 *

42

9.0 *

580

Medium chain acyl-CoA dehydrogenase deficiency Mucopolysaccharidosis type 2

9.0 *

418

Congenital adrenal hyperplasia

9.0 BP*

3366

9.0 * 9.0 BP 8.6 BP* 8.5 * 8.4 *

98555 Anophthalmia - microphthalmia 8.3 BP* 2444 Congenital pulmonary airway malformation 8.2 BP* 171 Primary sclerosing cholangitis 8.1

7.0 BP 7.0 * 7.0 * 7.0 7.0 BP 7.0 BP* 6.85 6.7 * 6.7 BP*

Isolated trigonocephaly 57145 SUNCT syndrome 238468 Hypohidrotic ectodermal dysplasia

6.7 BP*

206647 Myotonic dystrophy 42062 Iminoglycinuria

6.7

42062 Iminoglycinuria 50839 Cat-scratch disease

6.67 BP*

6.7 * 6.7 * 6.68 * 6.6 *

138

CHARGE syndrome

6.5 BP

553

Cushing syndrome

6.5 *

52759 Vasculitis

6.3 *

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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ORPHA Number

Disease or Group of diseases

887 VACTERL/VATER association 363958 17q21.31 microdeletion syndrome 733 Familial adenomatous polyposis

Estimated prevalence (/100,000)

6.25 BP* 6.25 * 6.0 *

790

Retinoblastoma

6.0 BP

221

Dermatomyositis

6.0 *

683

Progressive supranuclear palsy

6.0

521

Chronic myeloid leukemia

6.0 *

609

Tibial muscular dystrophy

6.0 *

46724 Cerebral arteriovenous malformation 252164 Benign schwannoma 524

Li-Fraumeni syndrome

6.0 * 6.0 * 6.0

55

Oculocutaneous albinism

5.9

635

Neuroblastoma

5.8 BP*

1037

Arthrogryposis multiplex congenita

5.7 BP*

85438 Enthesitis-related arthritis 881 Turner syndrome 963

5.7 * 5.5 BP*

Acromegaly

5.5

2440

Split hand-split foot malformation

5.4 BP*

2542

Isolated anophthalmia - microphthalmia

5.3 BP*

738

Porphyria

5.25

778

Rett syndrome

5.0 BP*

792

X-linked retinoschisis

5.0

469

Hereditary fructose intolerance

5.0 *

718

Isolated Pierre Robin syndrome

5.0 BP*

287

Ehlers-Danlos syndrome, classic type

5.0

Primary ciliary dyskinesia

5.0 BP*

244 685

Hereditary spastic paraplegia

5.0 *

43

X-linked adrenoleukodystrophy

5.0 BP

251

Multiple epiphyseal dysplasia

5.0 *

90309 Ehlers-Danlos syndrome type 1 85414 Systemic-onset juvenile idiopathic arthritis

5.0 *

280062 Calciphylaxis 98878 Hemophilia A

5.0 *

886

Usher syndrome

5.0 * 4.85 4.8 *

ORPHA Number

Disease or Group of diseases

1209

Estimated prevalence (/100,000)

Tricuspid atresia Juvenile rheumatoid factor-positive 85435 polyarthritis 85436 Juvenile psoriatic arthritis 2130 Hemimelia

4.2 BP*

93110 Posterior urethral valve 778 Rett syndrome

4.125 BP*

4.2 * 4.2 * 4.15 * 4.0 *

15

Achondroplasia

4.0 BP

564

Meckel syndrome

4.0 BP

819

Smith-Magenis syndrome

4.0

884

Tetrasomy 12p

4.0 BP*

1928

Congenital lobar emphysema

4.0 BP

3193 Supravalvular aortic stenosis 52417 MALT lymphoma 79140 Cutaneous neuroendocrine carcinoma

4.0 BP*

96169 Koolen-De Vries syndrome 96253 Cushing disease

4.0 *

95716 Familial thyroid dyshormonogenesis 101330 Porphyria cutanea tarda

4.0 *

99013 Spastic paraplegia type 7 178029 Central diabetes insipidus

4.0 *

96092 8p inverted duplication/deletion syndrome 803 Amyotrophic lateral sclerosis

3.9 BP*

79126 Acute interstitial pneumonia 98848 Indolent systemic mastocytosis

3.8 *

2467

Systemic mastocytosis

3.75

478

Kallmann syndrome

3.75 *

3378

Trisomy 13

3.7 BP*

3451

4.0 * 4.0 * 4.0 * 4.0 * 4.0 * 3.85 3.8 *

West syndrome Chronic inflammatory demyelinating 2932 polyneuropathy 3465 Worster-Drought syndrome 818 Smith-Lemli-Opitz syndrome

3.7 BP

60015 Enlarged parietal foramina 98976 Congenital glaucoma

3.7

3.7 * 3.7 * 3.7 BP* 3.6 BP*

88629 Tritanopia 98896 Duchenne muscular dystrophy

4.8 *

60041 Congenital heart block 269 Facioscapulohumeral dystrophy

4.54 BP 4.5 *

Hereditary neuropathy with liability to pressure palsies 1880 Ebstein malformation 2655 Thanatophoric dysplasia

85446 Wild type ABeta2M amyloidosis 175 Cartilage-hair hypoplasia

4.5 *

3205

Sturge-Weber syndrome

3.5 BP*

4.34 BP*

2103

Guillain-Barré syndrome

3.5 *

81

Antisynthetase syndrome

3.5

104

Leber hereditary optic neuropathy Neurogenic arthrogryposis multiplex 1143 congenita 3384 Truncus arteriosus 2116 Hartnup disease

4.78

4.3 4.3 BP* 4.3 BP 4.2

640

3.5 * 3.5 BP* 3.5 BP*

102 Multiple system atrophy 52416 Mantle cell lymphoma 95713 Athyreosis

3.5

95720 Thyroid hypoplasia

3.5

3.5 * 3.5 *

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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ORPHA Number

Disease or Group of diseases

217074 Rare carcinoma of pancreas 104008 Short bowel syndrome

Estimated prevalence (/100,000)

3.5 3.4 *

218

Darier disease

3.4 *

652

Multiple endocrine neoplasia type 1

3.3 *

905

Wilson disease

3.3

429

Hypochondroplasia

3.3 *

1172

Autosomal recessive cerebellar ataxia

3.3

98672 Autosomal dominant optic atrophy 98723 Hypoplastic right heart syndrome

3.3

182090 Pulmonary arterial hypertension 926 Acatalasemia

3.3 *

158

3.3 BP* 3.2 *

Systemic primary carnitine deficiency 100075 Gastric endocrine tumor 2322 Kabuki syndrome

3.2 BP*

50251 Pleural mesothelioma Acute inflammatory demyelinating 98916 polyradiculoneuropathy 93930 Bladder exstrophy 673 Malaria

3.1 *

3.2 * 3.1 *

3.1 * 3.05 BP 3.0 *

794

Saethre-Chotzen syndrome

3.0 BP*

136

CADASIL

3.0 *

282

Frontotemporal dementia

3.0 *

767

Polyarteritis nodosa

3.0 *

2745 Opitz G/BBB syndrome 36234 Bacterial toxic-shock syndrome 824 Myelofibrosis with myeloid metaplasia 70591 216694 238621 171673

Chronic thromboembolic pulmonary hypertension Congenitally corrected transposition of the great arteries Ileal pouch anal anastomosis related faecal incontinence Limbal stem cell deficiency

3.0 * 3.0

ORPHA Number

1872

Cone rod dystrophy 46,XX ovotesticular disorder of sex 2138 development Non-epidermolytic palmoplantar 2337 keratoderma 65 Leber congenital amaurosis 758 Pseudoxanthoma elasticum

2.5 BP 2.5 * 2.5 BP 2.5 *

Astrocytoma

46,XX testicular disorder of sex development 2.5

2.5 *

33069 Dravet syndrome 2.5 BP 75249 Familial isolated restrictive cardiomyopathy 2.5 * 97927 Peripheral resistance to thyroid hormones 2.5 * 93571 Dense deposit disease 100070 Progressive non-fluent aphasia Classic congenital adrenal hyperplasia due to 315311 21-hydroxylase deficiency, simple virilizing form 65 Leber congenital amaurosis 352731 Oculocutaneous albinism type 1

2.5

70588 Meconium aspiration syndrome 93928 Epispadias

2.44 *

330015 Lead poisoning 905 Wilson disease

2.3 *

2.5 * 2.5 * 2.5 2.5

2.4 BP* 98933 Multiple system atrophy, parkinsonian type 2.4 * 116 Beckwith-Wiedemann syndrome 2.3 BP* 39812 Graft versus host disease 2.3 *

3.0 *

304

3.0 *

2.5 *

393

2869

3.0 *

Estimated prevalence (/100,000)

94

3.0 *

3.0 BP

Disease or Group of diseases

Peutz-Jeghers syndrome

2.2 BP 2.2 BP

Epidermolysis bullosa simplex 137605 Legius syndrome 98895 Becker muscular dystrophy

2.2 BP*

217 Isolated Dandy-Walker malformation 70567 Cholangiocarcinoma 95 Friedreich ataxia

2.1 *

2.2 BP 2.2 BP* 2.1 2.0 *

653

Multiple endocrine neoplasia type 2

2.9 *

480

Kearns-Sayre syndrome

2.0 *

739

Prader-Willi syndrome

2.8 BP*

607

Nemaline myopathy

2.0 BP*

374

Goldenhar syndrome

2.8 BP*

280

2.0 BP*

506

Leigh syndrome

2.8 BP*

169802 Severe hemophilia A 626 Large congenital melanocytic nevus 399 99

Huntington disease Autosomal dominant cerebellar ataxia

2.75 *

861

Wolf-Hirschhorn syndrome Blepharophimosis - epicanthus inversus ptosis Treacher-Collins syndrome

2.7

352

Galactosemia

2.0 BP*

2.7

3346

Tracheal agenesis

2.0 BP*

63

2.8 *

1034

Gitelman syndrome Amniotic bands

2.0 2.0 BP*

Alport syndrome

2.0 *

3129

Sarcosinemia

2.0 BP

1699

Trisomy 12p

2.0 BP

2.5 *

2017

Sternal cleft

2.0 BP*

2.5 BP*

185

Scimitar syndrome

2.0 BP*

49382 Achromatopsia 2.7 6 3-methylcrotonyl-CoA carboxylase deficiency 2.65 BP* 79432 Oculocutaneous albinism type 2 2.55 358

126

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

2345 Isolated Klippel-Feil syndrome 54595 Craniopharyngioma 93323 Fibular hemimelia

2.0 *

98841 Anaplastic large cell lymphoma 217064 5-fluorouracil poisoning

2.0 *

157835 Paroxysmal hemicrania 168782 Childhood disintegrative disorder

2.0 *

657 Congenital isolated hyperinsulinism 93110 Posterior urethral valve 363203 Ring chromosome

2.0 BP

199

Cornelia de Lange syndrome

10

48,XXYY syndrome 79361 Inherited epidermolysis bullosa 35808 Malignant sex cord stromal tumor of ovary

2.0 * 2.0 * 2.0 * 2.0 * 2.0 * 2.0 BP 1.9 * 1.9 BP* 1.9 BP* 1.85 *

304

Epidermolysis bullosa simplex

1.8

675

Annular pancreas

1.8 BP*

53271 Muenke syndrome 664 Ornithine transcarbamylase deficiency 77

Aniridia 251076 8p23.1 microduplication syndrome Hydrocephalus with stenosis of the aqueduct 2182 of Sylvius Hydrocephalus with stenosis of the aqueduct 2182 of Sylvius 637 Neurofibromatosis type 2 2152 Mowat-Wilson syndrome 1848

Renal agenesis, bilateral

98879 Hemophilia B 394 Classic homocystinuria 899

1.8 BP*

ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

45452 Idiopathic neonatal atrial flutter 92050 Intestinal epithelial dysplasia

1.5 BP*

98757 Spinocerebellar ataxia type 3 98756 Spinocerebellar ataxia type 2

1.5

98755 Spinocerebellar ataxia type 1 168811 Malignant peritoneal mesothelioma

1.5

79269 Sanfilippo syndrome type A 195 Cat-eye syndrome

1.4 BP

247525 Citrullinemia type I 355 Gaucher disease

1.35 *

79434 Oculocutaneous albinism type 1B 79431 Oculocutaneous albinism type 1A

1.3

281090 Syndromic X-linked ichthyosis 1880 Ebstein malformation

1.3 *

1.5 BP* 1.5

1.5 * 168956 Hypereosinophilic syndrome 1.5 * 183 Eosinophilic granulomatosis with polyangiitis 1.5 512 Metachromatic leukodystrophy 1.47 BP* 1.35 BP* 1.3 BP 1.3 1.25 *

1.77 BP

2481

Neurocutaneous melanocytosis

1.25 *

1.75

628

Diastrophic dwarfism

1.2 *

1.72

2750

Orofaciodigital syndrome type 1

1.2 BP*

1.7 BP 1.7 1.7 *

46485 Superficial pemphigus Autosomal recessive polycystic kidney 731 disease 263432 Nevus of Ito 72 Angelman syndrome

1.2 * 1.17 * 1.17 * 1.1 BP*

1.7 BP*

289

Ellis Van Creveld syndrome

1.1 BP

1.7 BP*

2911

Poland syndrome

1.1 BP*

1.7 *

224

Neonatal diabetes mellitus

1.1 BP*

1.65 *

140874 Joubert syndrome and related disorders 275766 Idiopathic pulmonary arterial hypertension

1.1 BP

Walker-Warburg syndrome

1.65 BP*

183660 Severe combined immunodeficiency 1915 Fetal alcohol syndrome

1.65 BP*

377

Gorlin syndrome

1.1

1.6 BP*

487

64747 X-linked Charcot-Marie-Tooth disease 79241 Biotinidase deficiency

Krabbe disease

1.0 *

1.6 *

614

Thomsen and Becker disease

1.0

1.6 *

16

79241 Biotinidase deficiency 98895 Becker muscular dystrophy

Blue cone monochromatism

1.0

1.6 BP

16

Blue cone monochromatism

1.0 BP

1.53

1.1 *

681

192

Hypokalemic periodic paralysis

1.0 *

Coffin-Lowry syndrome

1.5

53

131

Albers-Schönberg osteopetrosis

1.0

Budd-Chiari syndrome

1.5 *

199

180

1.5 *

2019

Femur-fibula-ulna complex

1.5 BP*

389

Langerhans cell histiocytosis

1.5 *

217

Cornelia de Lange syndrome Glycogen storage disease due to phosphorylase kinase deficiency Isolated Dandy-Walker malformation

1.0 BP*

Choroideremia

137

Congenital disorder of glycosylation

1.5 BP*

33

Isovaleric acidemia

1.0 *

370

1.0 BP* 1.0 BP*

35689 Primary lateral sclerosis 641 Multifocal motor neuropathy

1.5 *

2308

Jacobsen syndrome

1.0 BP*

1.5

606

Proximal myotonic myopathy

1.0 *

71211 Neuromyelitis optica 45453 Incessant infant ventricular tachycardia

1.5 *

355

Gaucher disease

1.0 *

1.5 BP*

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

8

ORPHA Number

364 646

Disease or Group of diseases

Glycogen storage disease due to glucose-6phosphatase deficiency Niemann-Pick disease type C

2134

Atypical hemolytic-uremic syndrome Autosomal recessive limb-girdle muscular 267 dystrophy type 2A 1552 Currarino triad 189 Hidrotic ectodermal dysplasia

Estimated prevalence (/100,000)

1.0 BP 1.0 * 1.0 * 1.0 * 1.0 * 1.0 *

254

Spondylometaphyseal dysplasia 1.0 BP* Mayer-Rokitansky-Küster-Hauser syndrome 2578 1.0 BP* type 2 296 Enchondromatosis 1.0 * 647 Nijmegen breakage syndrome 1.0 BP 2924

Isolated polycystic liver disease 1.0 * Idiopathic and/or familial pulmonary arterial 422 1.0 * hypertension 3403 Uhl anomaly 1.0 BP 3449 Weill-Marchesani syndrome 1.0 616

Medulloblastoma

1.0 *

360

Glioblastoma

1.0

1900

Ehlers-Danlos syndrome, kyphoscoliotic type 1.0 BP

286

Ehlers-Danlos syndrome, vascular type

1.0 *

531

Miller-Dieker syndrome

1.0 BP*

396

Chronic hiccup Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Glutaryl-CoA dehydrogenase deficiency

1.0 *

5

1.0 BP*

ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

180242 Malignant tumor of fallopian tubes Glycogen storage disease due to liver 264580 phosphorylase kinase deficiency 141 Canavan disease 577 Mucolipidosis type III

1.0 *

444490 Familial chylomicronemia syndrome 33226 Waldenström macroglobulinemia

1.0 *

87503 Mal de Meleda 3169 Sirenomelia

1.0

79278 Autosomal erythropoietic protoporphyria 207 Crouzon disease

0.92 *

2131

0.9 BP*

Alternating hemiplegia of childhood

882 Tyrosinemia type 1 48162 Lewis-Sumner syndrome 581 Mucopolysaccharidosis type 3 576

Mucolipidosis type II

1.0 BP* 1.0 BP 1.0 BP* 1.0 * 0.98 BP 0.9 BP* 0.9 BP 0.9 * 0.87 BP* 0.84 BP*

99429 Complete androgen insensitivity syndrome 579 Mucopolysaccharidosis type 1

0.83

1461 Criss-cross heart 79361 Inherited epidermolysis bullosa 169793 Severe hemophilia B

0.8 BP*

0.82 BP Glycogen storage disease due to acid maltase 365 0.8 BP* deficiency 2346 Angioosteohypertrophic syndrome 0.8 BP* 813 Silver-Russell syndrome 0.8 BP* 0.8 * 0.8 *

1.0 BP

3312

Thalidomide embryopathy

0.77

Rhizomelic chondrodysplasia punctata Autosomal recessive limb-girdle muscular 34515 dystrophy type 2I 67043 Acanthamoeba keratitis 51577 Cobblestone lissencephaly

1.0 *

213

Cystinosis

0.75 BP

181

X-linked hypohidrotic ectodermal dysplasia

0.75 BP* 0.75 BP*

79435 Oculocutaneous albinism type 4 Glycogen storage disease due to glucose-679258 phosphatase deficiency type a 77259 Gaucher disease type 1 91378 Hereditary angioedema

1.0

25 177

1.0 *

354

GM1 gangliosidosis

1.0 *

667

Autosomal recessive malignant osteopetrosis 0.75 BP*

1.0 BP*

1501

1.0 BP* 1.0 *

1.0 * 90060 Diffuse alveolar hemorrhage 1.0 * 98863 X-linked Emery-Dreifuss muscular dystrophy 1.0 98863 X-linked Emery-Dreifuss muscular dystrophy 1.0 BP 96263 48,XXXY syndrome Congenital hypothyroidism due to 95715 transplacental passage of maternal TSHbinding inhibitory antibodies 94068 Spondyloepiphyseal dysplasia congenita 93685 Localized Castleman disease

1.0 BP* 1.0 * 1.0 BP* 1.0

99789 Dentin dysplasia type I 1.0 * 163703 Febrile infection-related epilepsy syndrome 1.0 *

Adrenocortical carcinoma Congenital adrenal hyperplasia due to 1190795 beta-hydroxylase deficiency Congenital adrenal hyperplasia due to 95699 cytochrome P450 oxidoreductase deficiency 487 Krabbe disease 464 Incontinentia pigmenti

0.75 * 0.75 BP* 0.75 BP* 0.7 BP 0.7 BP*

392

Holt-Oram syndrome

0.7 BP*

726

Alpers-Huttenlocher syndrome

0.7 BP*

110

Bardet-Biedl syndrome

0.7 *

303 Dystrophic epidermolysis bullosa 216804 Osteogenesis imperfecta type 2 93473 Hurler syndrome

0.7 0.7 BP* 0.7 BP*

580

Mucopolysaccharidosis type 2

0.68 BP

796

Sandhoff disease

0.67 BP*

124

Blackfan-Diamond anemia

0.67 BP*

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

9

ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

511

Maple syrup urine disease

0.67 BP

2591

Infantile myofibromatosis

0.67 BP*

ORPHA Number

281097 Autosomal recessive congenital ichthyosis 93473 Hurler syndrome

3282

Multifocal atrial tachycardia

0.67 BP

201

1335

Pentalogy of Cantrell

0.67 BP

100

90053 Hematopoietic stem cell transplantation 84 Fanconi anemia

0.65 * 0.62 BP*

783

Rubinstein-Taybi syndrome

0.6 BP*

474

Jeune syndrome

0.6 BP*

3287 994 2345

Takayasu arteritis

0.6 *

Fetal akinesia deformation sequence

0.6 BP*

Isolated Klippel-Feil syndrome

0.6 BP*

79168 Disorder of bile acid synthesis 79098 Sympathetic ophthalmia

0.6 *

98809 Paroxysmal kinesigenic dyskinesia Progressive supranuclear palsy - corticobasal 240103 syndrome 248111 Juvenile Huntington disease 169796 Moderately severe hemophilia B

0.6

169799 Mild hemophilia B 54 X-linked recessive ocular albinism

0.6 *

0.6 *

0.6 * 0.6 * 0.6 * 0.58 BP*

562

Pulmonary arterial hypertension associated 0.57 * with congenital heart disease McCune-Albright syndrome 0.55 *

313

Lamellar ichthyosis 96264 49,XXXXY syndrome 79276 Acute intermittent porphyria

0.55 *

93929 Cloacal exstrophy 682 Hyperkalemic periodic paralysis

0.54 BP

275803

0.55 BP* 0.54 * 0.5 *

23

Argininosuccinic aciduria

0.5 *

255

Dopa-responsive dystonia

0.5

Inclusion body myositis

0.5 *

611 828

Stickler syndrome

0.5 BP*

634

Netherton syndrome

0.5 BP*

634

Netherton syndrome

0.5 *

902

Werner syndrome

0.5 *

3427

Double outlet left ventricle

0.5 BP

811

Shwachman-Diamond syndrome

0.5 BP

747

Autoimmune pulmonary alveolar proteinosis 0.5

Disease or Group of diseases

Cowden syndrome

Ataxia-telangiectasia Congenital adrenal hyperplasia due to 1190795 beta-hydroxylase deficiency 379 Chronic granulomatous disease 23 Argininosuccinic aciduria

Estimated prevalence (/100,000)

0.5 * 0.5 * 0.5 * 0.49 * 0.47 * 0.46 BP 0.46 BP

676

Hereditary chronic pancreatitis

0.43 *

52

Alagille syndrome

0.4 BP*

2869

Peutz-Jeghers syndrome

0.4 *

1452

Cleidocranial dysplasia

0.4 BP*

915

Aarskog-Scott syndrome Autosomal dominant optic atrophy plus 1215 syndrome 2315 Johanson-Blizzard syndrome 3008 Pyruvate carboxylase deficiency

0.4 BP* 0.4 * 0.4 BP* 0.4 BP*

256

Early-onset generalized limb-onset dystonia 0.4 *

503

Autosomal dominant Larsen syndrome

0.4 BP*

42738 Severe congenital neutropenia 88 Idiopathic aplastic anemia

0.4 BP*

77293 Niemann-Pick disease type B 217085 Mucopolysaccharidosis type 2, severe form Non-acquired isolated growth hormone 631 deficiency 99885 Permanent neonatal diabetes mellitus 3440 Waardenburg syndrome

0.4 *

290

Congenital rubella syndrome

43393 Lambert-Eaton myasthenic syndrome 510 Lesch-Nyhan syndrome

0.4 * 0.4 BP* 0.39 0.38 BP* 0.37 BP* 0.35 BP* 0.35 0.34 BP*

96

Ataxia with vitamin E deficiency

0.33 *

565

Menkes disease

0.33 BP*

327

Congenital factor VII deficiency

0.33 *

140 Campomelic dysplasia 98850 Aggressive systemic mastocytosis 79473 Porphyria variegata

0.33 BP* 0.33 * 0.32 *

261

Axenfeld-Rieger syndrome Combined deficiency of factor V and factor 35909 VIII 122 Birt-Hogg-Dubé syndrome 64742 Pleuropulmonary blastoma

0.5 *

Carbamoyl-phosphate synthetase 1 deficiency Emery-Dreifuss muscular dystrophy

394

Classic homocystinuria

0.3 BP

0.5 *

258

Congenital muscular dystrophy type 1A

0.3 *

79269 Sanfilippo syndrome type A 79242 Holocarboxylase synthetase deficiency

0.5 *

98249 Ehlers-Danlos syndrome

0.5 BP*

782

0.5 * 0.5 BP* 0.5 BP*

147

0.31 0.3 *

84

Fanconi anemia 0.3 Autosomal dominant popliteal pterygium 1300 0.3 syndrome Mirror polydactyly - vertebral segmentation 3004 0.3 * limbs defects 633 Laron syndrome 0.3 *

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

10

ORPHA Number

Disease or Group of diseases

2299

Estimated prevalence (/100,000)

Aortic arch interruption Severe combined immunodeficiency due to 277 adenosine deaminase deficiency 590 Congenital myasthenic syndrome Autosomal recessive limb-girdle muscular 219 dystrophy type 2F 56970 Transmissible spongiform encephalopathy Congenital non-bullous ichthyosiform 79394 erythroderma 90647 Jervell and Lange-Nielsen syndrome 90079 Anthracycline extravasations

0.3 BP*

229717 Isolated agammaglobulinemia 182050 MYH9-related disease

0.3

294963 Popliteal pterygium syndrome 324964 Chronic recurrent multifocal osteomyelitis

0.3 *

99886 Transient neonatal diabetes mellitus 845 Tay-Sachs disease

0.3 BP*

0.3 BP* 0.3 * 0.3 * 0.3 * 0.3 * 0.3 0.3 * 0.3 * 0.3 0.28 BP

811

Shwachman-Diamond syndrome

0.28

191

Cockayne syndrome

0.27 BP*

702

Pelizaeus-Merzbacher disease

0.25 *

528

Berardinelli-Seip congenital lipodystrophy

0.25 *

678

Papillon-Lefèvre syndrome X-linked dominant chondrodysplasia 35173 punctata 77292 Niemann-Pick disease type A Pulmonary arterial hypertension associated 275798 with connective tissue disease 910 Xeroderma pigmentosum 324 Fabry disease

0.25 0.25 BP* 0.25 BP* 0.25 * 0.23 BP* 0.22 BP*

ORPHA Number

Disease or Group of diseases

Hypohidrotic ectodermal dysplasia with immunodeficiency 93598 Primary hyperoxaluria type 1 99870 Letterer-Siwe disease 98813

Estimated prevalence (/100,000)

0.2 BP* 0.2 * 0.2 *

238583 Hyperphenylalaninemia 178478 Infant botulism

0.2

209916 Extraskeletal myxoid chondrosarcoma 1361 Carnosinemia

0.2 *

1456

Atypical coarctation of aorta

0.2 BP* 0.2 BP 0.17 BP*

407

Glycine encephalopathy 0.17 * 79404 Junctional epidermolysis bullosa, Herlitz type 0.17 BP 280219 Pelizaeus-Merzbacher disease, classic form 0.17 * 583 Mucopolysaccharidosis type 6 0.16 BP* 85

Congenital dyserythropoietic anemia

0.16 BP*

335

Congenital fibrinogen deficiency

0.15 *

538

Lymphangioleiomyomatosis

0.15

223

Nephrogenic diabetes insipidus 79430 Hermansky-Pudlak syndrome Pantothenate kinase-associated 157850 neurodegeneration 118 Beta-mannosidosis 763 Pycnodysostosis 3463

Wolfram syndrome

183669 Agammaglobulinemia 1308 C syndrome Autosomal dominant medullary cystic kidney 34149 disease with or without hyperuricemia 61 Alpha-mannosidosis Glycogen storage disease due to glycogen 367 branching enzyme deficiency 512 Metachromatic leukodystrophy 906 Wiskott-Aldrich syndrome

0.15 * 0.15 0.15 * 0.14 BP* 0.13 0.13 0.13 * 0.11 * 0.11 * 0.1 *

47

X-linked agammaglobulinemia

0.22

111

Barth syndrome

0.22 *

436

Hypophosphatasia

0.21 BP*

447

Paroxysmal nocturnal hemoglobinuria

0.2 *

628

534

Diastrophic dwarfism

0.1 BP*

Oculocerebrorenal syndrome of Lowe

0.2

205

893

Crigler-Najjar syndrome

0.1 BP*

WAGR syndrome Neurodegeneration with brain iron accumulation Dubowitz syndrome

0.2 BP

773

Refsum disease

0.1 *

0.2 *

1452

Cleidocranial dysplasia

0.1

1775

Dyskeratosis congenita

0.1 *

3320

Thrombocytopenia - absent radius

0.2 BP*

204

Creutzfeldt-Jakob disease

0.1 *

3006

Pyridoxine-dependent epilepsy

0.2 BP*

1959

Evans syndrome

0.1 *

2052

Fraser syndrome

0.2 BP*

3198

Stiff person syndrome and related disorders 0.1 *

110

Bardet-Biedl syndrome Severe combined immunodeficiency due to adenosine deaminase deficiency Propionic acidemia Autosomal recessive limb-girdle muscular dystrophy type 2C

0.2 BP*

326

Congenital factor V deficiency

0.1 *

507

Leishmaniasis

0.1 *

0.2 *

3329

Tibial aplasia - ectrodactyly

0.1 *

0.2 *

329

Congenital factor XI deficiency

0.1 *

2686

Cyclic neutropenia Mitochondrial neurogastrointestinal encephalomyopathy

0.1 *

385 235

277 35 353

0.2 BP*

0.2 *

298

0.1 BP 0.1 * 0.1 *

0.1 *

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

11

ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

ORPHA Number

Disease or Group of diseases

Estimated prevalence (/100,000)

225

Maternally-inherited diabetes and deafness 0.1 *

227

Diphallia

0.02 BP

209

Cutis laxa

0.1 BP*

584

Mucopolysaccharidosis type 7

0.01 *

0.1 *

3169

31824 Colchicine poisoning Autosomal recessive limb-girdle muscular 119 dystrophy type 2E 142 Anaplastic thyroid carcinoma 73274 Acquired hemophilia Congenital adrenal hyperplasia due to 17alpha-hydroxylase deficiency 93262 Crouzon syndrome - acanthosis nigricans 93322 Tibial hemimelia 90793

0.1 * 0.1 * 0.1 * 0.1 *

Sirenomelia 77260 Gaucher disease type 2 90308 Klippel-Trénaunay syndrome 740

Hutchinson-Gilford progeria syndrome Poliomyelitis in patients with 330009 immunodeficiencies deemed at risk 391474 Frontorhiny

0.01 0.01 * 0.007 * 0.005 8.0E-4 * 0.0

0.1 BP 0.1 BP*

86834 Juvenile myelomonocytic leukemia 98810 Paroxysmal non-kinesigenic dyskinesia

0.1 *

99842 Leukocyte adhesion deficiency type I 247257 Inhalational anthrax

0.1 *

48818 Aceruloplasminemia 79270 Sanfilippo syndrome type B

0.09

0.1

0.1 * Adult-onset proximal spinal muscular 209335 0.1 * atrophy, autosomal dominant Mitochondrial membrane protein-associated 289560 0.1 neurodegeneration 391665 Homozygous familial hypercholesterolemia 0.1 2485 Melorheostosis 0.09 *

Cushing syndrome due to macronodular 189427 adrenal hyperplasia 275777 Heritable pulmonary arterial hypertension 726 Alpers-Huttenlocher syndrome 42738 Severe congenital neutropenia Neonatal acute respiratory distress due to 217563 SP-B deficiency 337 Fibrodysplasia ossificans progressiva 2442 X-linked lymphoproliferative disease

0.09 * 0.08 * 0.08 * 0.07 * 0.07 0.067 BP 0.05 0.05 *

2788

Osteoporosis - pseudoglioma

0.05 *

325

Congenital factor II deficiency

0.05 *

331

Congenital factor XIII deficiency

0.05 *

77261 Gaucher disease type 3 309294 Sialidosis

0.05 *

99718 Leber plus disease Primary pigmented nodular adrenocortical 189439 disease 69087 Naegeli-Franceschetti-Jadassohn syndrome Congenital muscular dystrophy with integrin 34520 alpha-7 deficiency 280210 Pelizaeus-Merzbacher disease, connatal form Pelizaeus-Merzbacher disease, transitional 280224 form 93976 Anotia 740 Hutchinson-Gilford progeria syndrome

0.04 *

0.05 BP*

0.04 * 0.035 * 0.03 * 0.03 * 0.03 * 0.028 BP* 0.025 BP

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

12

List of diseases or groups of diseases by decreasing incidence ORPHA Number

Disease or Group of diseases

69665 Intrahepatic cholestasis of pregnancy 178045 Transient congenital hypothyroidism 99828 Dengue fever 94093 Neuroleptic malignant syndrome 874

Adult heart tumor

3389 Tuberculosis 673 Malaria 418959 Squamous cell carcinoma of stomach 65250 Perineural cyst 558

Marfan syndrome

2810 Idiopathic facial palsy 507 Leishmaniasis

Estimated incidence(/100,000)

1000.0* 1000.0* 714.0 170.0 140.9* 139.0 73.0 55.0 50.0* 25.0* 25.0 25.0

178320 Acute lung injury 91546 Lyme disease

25.0*

63443 Rare epithelial tumor of stomach 98715 Uveitis

18.6*

813

Silver-Russell syndrome

21.9 17.0* 15.5*

ORPHA Number

Disease or Group of diseases

3099 Rheumatic fever 70567 Cholangiocarcinoma 217074 Rare carcinoma of pancreas 2929 Juvenile polyposis syndrome 2032 Idiopathic pulmonary fibrosis 182130 Tumor of endocrine glands 548 Leprosy Infant acute respiratory distress 70587 syndrome 36205 Collagenous colitis 100087 Thyroid tumor 363472 Tumor of testis and paratestis 100088 Thyroid carcinoma

Estimated incidence(/100,000)

5.0* 4.2 3.9 3.85* 3.81* 3.75* 3.7 3.5* 3.35 3.2 3.15* 3.1

186

Primary biliary cirrhosis

3.0

360

Glioblastoma

3.0

96061 Mosaic trisomy 8 99745 Typhoid Complete androgen insensitivity 99429 syndrome Familial isolated dilated 154 cardiomyopathy 513 Acute lymphoblastic leukemia 95716 Familial thyroid dyshormonogenesis

3.0* 3.0* 3.0* 2.91* 2.75* 2.67

15.0*

70

Proximal spinal muscular atrophy

2.6*

13.35*

877

Endocrine tumor

2.53*

268316 Complication in hemodialysis Carcinoma of gallbladder and 56044 extrahepatic biliary tract 547 Non-Hodgkin lymphoma 1546 Cryptococcosis

13.0*

2038 Pulmonary arteriovenous fistula 519 Acute myeloid leukemia

435 Ito hypomelanosis 137839 Lemierre syndrome 2209 Maternal phenylketonuria

10.85*

3467 Hereditary xanthinuria Squamous cell carcinoma of head and 67037 neck 94 Astrocytoma 1941 Juvenile absence epilepsy

9.05*

70482 Carcinoma of esophagus 3002 Immune thrombocytopenic purpura

7.0

461 418

448

Recessive X-linked ichthyosis Congenital adrenal hyperplasia

Hemophilia

29073 Multiple myeloma 58220 Microscopic colitis

12.0 11.6* 11.0* 10.0* 10.0*

8.7 8.0* 7.5* 6.75* 6.25* 6.0

Chronic recurrent multifocal 324964 osteomyelitis 98293 Hodgkin lymphoma 391 Classic Hodgkin lymphoma 352

Galactosemia

2.5 2.5 2.5 2.4* 2.38* 2.1*

79239 Classic galactosemia 98375 Autoimmune hemolytic anemia

2.1*

50251 Pleural mesothelioma 102 Multiple system atrophy

1.9*

2.02* 1866 Focal, segmental or multifocal dystonia 2.0* 729 Polycythemia vera 1.9*

Testicular seminomatous germ cell 842 tumor 355 Gaucher disease 139417 Acute transverse myelitis

1.8 1.71* 1.7* 1.6

6.0*

553

Cushing syndrome

1.55*

5.4*

512

Metachromatic leukodystrophy

1.5*

5.25 171901 Primary cutaneous T-cell lymphoma 5.2* 99977 Squamous cell carcinoma of esophagus 5.2

92

Juvenile idiopathic arthritis

1.5*

35

Propionic acidemia

1.5

618

Familial melanoma

1.5*

182095 Interstitial lung disease 146 Differentiated thyroid carcinoma

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

13

ORPHA Number

Disease or Group of diseases

Estimated incidence(/100,000)

26106 Hereditary diffuse gastric cancer 52688 Myelodysplastic syndrome

1.5*

2103 Guillain-Barré syndrome 801 Scleroderma

1.45

803 Amyotrophic lateral sclerosis 250923 Isolated aniridia 77 Aniridia 635

Neuroblastoma

521

Chronic myeloid leukemia Proximal spinal muscular atrophy type 83418 2 Non-seminomatous germ cell tumor of 363494 testis 2137 Chronic autoimmune hepatitis Epstein-Barr virus-associated gastric 313920 carcinoma 549 Legionellosis Proximal spinal muscular atrophy type 83419 3 398043 Malignant tumor of penis 91349 Non-functioning pituitary adenoma

1.5* 1.41 1.35 1.31* 1.3* 1.26 1.25* 1.23* 1.21* 1.2 1.2 1.1* 1.1* 1.075* 1.05

ORPHA Number

Disease or Group of diseases

Estimated incidence(/100,000)

83597 Acute disseminated encephalomyelitis 0.6* 101330 Porphyria cutanea tarda 0.6* 780 Rhabdomyosarcoma 0.59* 178566 Mycosis fungoides and variants 0.59* 732 Polymyositis 398058 Squamous cell carcinoma of penis 221 Dermatomyositis

0.585*

99892 ACTH-dependent Cushing syndrome 589 Myasthenia gravis

0.55

99971 Well-differentiated liposarcoma 191 Cockayne syndrome

0.51*

2584 Classic mycosis fungoides 980 Absence of the pulmonary artery

0.5*

39044 Uveal melanoma 820 Sneddon syndrome

0.5*

T-cell large granular lymphocyte 86872 leukemia 101959 Chronic primary adrenal insufficiency 399 Huntington disease 83484 St. Louis encephalitis 36426 Stevens-Johnson syndrome

0.57* 0.55* 0.53 0.5* 0.5* 0.4* 0.4* 0.4* 0.38 0.38*

848

Beta-thalassemia

1.0

710

Pfeiffer syndrome

1.0*

963

Acromegaly

0.35

1.0*

728

Relapsing polychondritis

0.35

727

Microscopic polyangiitis Malignant peripheral nerve sheath 3148 tumor 400 Cystic echinococcosis 2781 Osteopetrosis

1.0 1.0* 1.0*

44890 Gastrointestinal stromal tumor 1.0 824 Myelofibrosis with myeloid metaplasia 1.0* 69078 Liposarcoma 1.0* 54595 Craniopharyngioma 157798 Hyperplastic polyposis syndrome 209964 Solitary rectal ulcer syndrome

0.337

0.3*

0.65

0.29* 79140 Cutaneous neuroendocrine carcinoma 0.27 99970 Dedifferentiated liposarcoma 0.27* Proximal spinal muscular atrophy type 83330 0.26* 1 168999 Malignant melanoma of the mucosa 0.26* 97279 Insulinoma 0.25

0.65*

139423 Idiopathic acute transverse myelitis

0.25*

1.0 1.0*

0.81* 0.8*

Idiopathic achalasia

0.77

Primary cutaneous lymphoma

0.75*

900

Granulomatosis with polyangiitis

0.7*

46484 Oligodendroglial tumor 100070 Progressive non-fluent aphasia

0.7*

99976 Adenocarcinoma of esophagus 683 Progressive supranuclear palsy

0.7

79139 Japanese encephalitis

0.34*

178478 Infant botulism Acute generalized exanthematous 293173 pustulosis 93672 Juvenile dermatomyositis 58017 Hairy cell leukemia

1.0

542

Primary sclerosing cholangitis

Listeriosis

0.35*

0.32

930

171

533

0.35*

1070 Anisakiasis Proximal spinal muscular atrophy type 83420 4 1930 Herpes simplex encephalitis Hereditary pheochromocytoma29072 paraganglioma 873 Desmoid tumor 52417 MALT lymphoma

2023 Undifferentiated pleomorphic sarcoma 0.9* 2467 Systemic mastocytosis 0.9* 33226 Waldenström macroglobulinemia 223727 Bone sarcoma

49041 IgG4-related retroperitoneal fibrosis 329217 Cerebral sinovenous thrombosis 33276 Kaposi sarcoma

0.36*

0.7* 0.65

0.32* 0.3 0.3 0.3* 0.3*

0.3 0.295

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

14

ORPHA Number

Disease or Group of diseases

Estimated incidence(/100,000)

329977 Classic endocrine tumor of appendix 55880 Chondrosarcoma

0.25

668 Osteosarcoma 1332 Medullary thyroid carcinoma 97253 Pancreatic endocrine tumor

0.23*

301

Ependymal tumor

96253 Cushing disease 251636 Ependymoma Primary hepatic neuroendocrine carcinoma 3287 Takayasu arteritis 95455 Toxic epidermal necrolysis

100085

Primary cutaneous CD30+ T-cell 541 lymphoproliferative disease Eosinophilic granulomatosis with 183 polyangiitis 543 Burkitt lymphoma 3398 Thymic epithelial neoplasm

0.24* 0.22* 0.21* 0.2* 0.2* 0.2* 0.2 0.19* 0.19 0.18* 0.18* 0.17* 0.17*

142

Anaplastic thyroid carcinoma

0.17*

284

Alveolar echinococcosis

0.16*

204

Creutzfeldt-Jakob disease

0.15

2495 Meningioma Transmissible spongiform 56970 encephalopathy 33402 Pediatric hepatocellular carcinoma 654 Nephroblastoma

0.15*

99867 Thymoma 319 Ewing sarcoma

0.14*

Malignant sex cord stromal tumor of ovary 182114 Rare urogenital tumor 913 Zollinger-Ellison syndrome 35808

2086 Optic pathway glioma Nodular lymphocyte predominant 86893 Hodgkin lymphoma 616 Medulloblastoma 520 Acute promyelocytic leukemia 112

Bartter syndrome

509

Leptospirosis Autosomal dominant hyper-IgE 2314 syndrome 2382 Lennox-Gastaut syndrome 514 Acute monoblastic leukemia

0.15* 0.15* 0.14*

Disease or Group of diseases

Estimated incidence(/100,000)

98919 Miller-Fisher syndrome 228371 Foodborne botulism 178475 Wound botulism

0.1*

79277 Congenital erythropoietic porphyria 790 Retinoblastoma

0.065*

1267 Botulism 99969 Pleomorphic liposarcoma 99931 Idiopathic pulmonary hemosiderosis

0.05*

0.1*

0.1* Anti-glomerular basement membrane 375 0.08* disease 35807 Malignant germ cell tumor of ovary 0.08* 73274 Acquired hemophilia 0.08

331

Congenital factor XIII deficiency

248111 Juvenile Huntington disease 300385 Pituitary carcinoma Autoimmune pulmonary alveolar 747 proteinosis 357034 Non-hereditary retinoblastoma 2573 Moyamoya disease 290

Congenital rubella syndrome

0.05* 0.05* 0.0425* 0.04* 0.04* 0.04* 0.04 0.038* 0.035* 0.03*

1501 Adrenocortical carcinoma 33355 Reticular dysgenesis

0.03*

46487 Acquired epidermolysis bullosa 99865 Spermatocytic seminoma

0.03*

329984 Goblet cell carcinoma 449 Hepatoblastoma

0.025

0.03* 0.03* 0.02*

0.13*

1957 Esthesioneuroblastoma 1183 Opsoclonus-myoclonus syndrome

0.02*

0.13*

143

0.02*

0.13* 0.125 0.12 0.12 0.11* 0.11* 0.1* 0.1* 0.1* 0.1* 0.1*

Cardiodysrhythmic potassium-sensitive 0.1* periodic paralysis 26790 Pseudomyxoma peritonei 0.1 53035 Caroli disease 0.1 37553

99967 Myxoid/round cell liposarcoma

ORPHA Number

Parathyroid carcinoma

0.02*

99928 Placental site trophoblastic tumor 251909 Pineoblastoma

0.02*

251679 Astroblastoma 363489 Sex cord-stromal tumor of testis

0.02*

31837 Pulmonary venoocclusive disease 538 Lymphangioleiomyomatosis

0.015*

79276 Acute intermittent porphyria Autosomal erythropoietic 79278 protoporphyria 2030 Fibrosarcoma 55881 Adamantinoma

0.013*

251899 Choroid plexus carcinoma 79473 Porphyria variegata

0.01*

Pleuropulmonary blastoma family 284343 tumor susceptibility syndrome 97280 Glucagonoma 97283 Somatostatinoma

0.02* 0.02* 0.0135

0.012* 0.01* 0.01* 0.008* 0.007 0.005* 0.0025*

0.1*

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

15

List of diseases or groups of diseases by decreasing number of published cases or families Disease or Group of diseases

319218 Ebola hemorrhagic fever 50918 Kikuchi-Fujimoto disease 2309 Pachyonychia congenita 158014 Rosaï-Dorfman disease 64

Alström syndrome

1917 Fetal methylmercury syndrome 83312 Rickettsialpox 85

Congenital dyserythropoietic anemia

99825 Nipah virus disease 167

Chédiak-Higashi syndrome

26

Methylmalonic acidemia with homocystinuria

2138 46,XX ovotesticular disorder of sex development 2930 Cronkhite-Canada syndrome 3261 Autoimmune lymphoproliferative syndrome 34526 Familial primary hypomagnesemia 42642 PFAPA syndrome 35687 Erdheim-Chester disease 69077 Rhabdoid tumor 73256 Central neurocytoma 79282

Methylmalonic acidemia with homocystinuria, type cblC

99826 Marburg hemorrhagic fever 85448 AGel amyloidosis 22

4-hydroxybutyric aciduria

79312 411593 649

Number of published cases ORPHA Number

ORPHA Number

Number of cases

28220 Cases 1052 Cases 1000 Cases 1000 Cases 950 Cases 800 Cases 800 Cases 740 Cases 556 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 500 Cases 475 Cases 450 Cases

125 35125 100025 3348 352540 238606 83453 2968 64741 85458 838 1556 570 3071 157 184 1340 1328 1896 2092 2909 1467 2330 3347

Disease or Group of diseases

Number of cases

Vitamin B12-unresponsive methylmalonic acidemia type mut-

450 Cases 404 Insulin autoimmune syndrome Cases 400 Norrie disease Cases 400 Bloom syndrome Cases 400 Epidermal nevus syndrome Cases 400 Alpha-heavy chain disease Cases 400 Tracheobronchopathia osteochondroplastica Cases 400 Oncogenic osteomalacia Cases 390 Primary orthostatic tremor Cases 380 Vulvovaginal gingival syndrome Cases 350 Leukocyte adhesion deficiency Cases 350 Pulmonary blastoma Cases 350 Hereditary cerebral hemorrhage with amyloidosis Cases 304 Susac syndrome Cases 300 Cutis marmorata telangiectatica congenita Cases 300 Moebius syndrome Cases 300 Costello syndrome Cases 300 Carnitine palmitoyltransferase II deficiency Cases 300 Cherubism Cases 300 Cardiofaciocutaneous syndrome Cases 300 Camurati-Engelmann disease Cases 300 EEC syndrome Cases 300 Focal dermal hypoplasia Cases 300 Rothmund-Thomson syndrome Cases 300 Cogan syndrome Cases 300 Kasabach-Merritt syndrome Cases 300 Mounier-Kühn syndrome Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

16

ORPHA Number

Disease or Group of diseases

Number of cases

300 Cases 300 41 Dyschromatosis symmetrica hereditaria Cases 300 482 Kimura disease Cases 300 525 Lichen planopilaris Cases 300 840 Syringocystadenoma papilliferum Cases 300 73 Gorham-Stout disease Cases 300 83469 Desmoplastic small round cell tumor Cases 300 99147 Acquired von Willebrand syndrome Cases Carnitine palmitoyl transferase II deficiency, 300 228302 myopathic form Cases 300 247245 Superficial siderosis Cases 300 167635 Scleromyxedema Cases 300 206569 Autoimmune necrotizing myopathy Cases 300 237 Duplication of urethra Cases 300 501 Lafora disease Cases 296 500 Noonan syndrome with multiple lentigines Cases Acute encephalopathy with biphasic seizures and 283 363549 late reduced diffusion Cases 280 2070 Eosinophilic gastroenteritis Cases Capillary malformation - arteriovenous 261 137667 malformation Cases 250 2908 Kindler syndrome Cases 250 79087 Partial acquired lipodystrophy Cases 250 100006 ABeta amyloidosis, Dutch type Cases 250 98954 Meesmann corneal dystrophy Cases 250 163634 Maffucci syndrome Cases 250 373 Simpson-Golabi-Behmel syndrome Cases 250 90283 Lupus erythematosus tumidus Cases 246 199318 15q13.3 microdeletion syndrome Cases 243 2710 Oculodentodigital dysplasia Cases 530

Lipoid proteinosis

ORPHA Number

Disease or Group of diseases

Number of cases

241 Cases Megacystis-microcolon-intestinal hypoperistalsis 230 syndrome Cases 220 Lhermitte-Duclos disease Cases 205 Muir-Torre syndrome Cases 204 Pachydermoperiostosis Cases 203 Micro syndrome Cases 201 Trichothiodystrophy Cases 200 Monosomy 18p Cases 200 Cohen syndrome Cases 200 Blue rubber bleb nevus Cases 200 Eosinophilic fasciitis Cases Alpha-thalassemia-X-linked intellectual disability 200 syndrome Cases 200 Gollop-Wolfgang complex Cases 200 Bilateral striopallidodentate calcinosis Cases 200 3M syndrome Cases 200 Muckle-Wells syndrome Cases 200 Marinesco-Sjögren syndrome Cases 200 Hyperimmunoglobulinemia D with periodic fever Cases 200 Gyrate atrophy of choroid and retina Cases 200 CINCA syndrome Cases 200 X-linked lissencephaly with abnormal genitalia Cases 200 Erythrokeratodermia variabilis Cases 200 Epidermodysplasia verruciformis Cases 200 Glycogen storage disease due to GLUT2 deficiency Cases 200 Tufted angioma Cases 200 Denys-Drash syndrome Cases 200 Hypocomplementemic urticarial vasculitis Cases

169105 Good syndrome 2241 65285 587 2796 2510 33364 1598 193 1059 3165 847 1986 1980 2616 575 559 343 414 1451 452 317 302 2088 1063 220 36412

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

17

ORPHA Number

Disease or Group of diseases

523

Hereditary leiomyomatosis and renal cell cancer

679

Malignant atrophic papulosis

66630 Congenital pseudoarthrosis of clavicle 48377 Subcorneal pustular dermatosis 48686 Primary effusion lymphoma 48652 Monosomy 22q13 79277 Congenital erythropoietic porphyria 79255 GM1 gangliosidosis type 1 75563 X-linked sideroblastic anemia 91385 Acquired angioedema 97360 Robinow syndrome 97231 Ligneous conjunctivitis 139436 Multicentric reticulohistiocytosis 139491 Hemochromatosis type 4 137867 Madras motor neuron disease 99050 Pulmonary artery coming from the aorta 220407 Limited systemic sclerosis 221016 Rothmund-Thomson syndrome type 2 199267 Infantile digital fibromatosis 293848 Right temporal lobar atrophy 306516

Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis

1540 Jackson-Weiss syndrome 402035 Eosinophilic colitis 28

Vitamin B12-responsive methylmalonic acidemia

1465 Coffin-Siris syndrome 293381 Epithelial recurrent erosion dystrophy 1475 Renal coloboma syndrome

Number of cases

200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 200 Cases 196 Cases 192 Cases 190 Cases 186 Cases 180 Cases

ORPHA Number

Disease or Group of diseases

Number of cases

180 Cases 173 98960 Thiel-Behnke corneal dystrophy Cases Celiac disease, epilepsy and cerebral calcification 170 1459 syndrome Cases Megalencephaly-capillary malformation170 60040 polymicrogyria syndrome Cases 170 97685 17q11 microdeletion syndrome Cases 170 252212 Malignant triton tumor Cases 170 324636 Autoerythrocyte sensitization syndrome Cases 160 1522 Craniometaphyseal dysplasia Cases 160 1359 Carney complex Cases Congenital cataracts - facial dysmorphism 160 48431 neuropathy Cases 154 300324 Persistent polyclonal B-cell lymphocytosis Cases 150 226 Dihydropteridine reductase deficiency Cases 150 3467 Hereditary xanthinuria Cases 150 3103 Roberts syndrome Cases 150 2048 Foix-Chavany-Marie syndrome Cases 150 2108 Hallermann-Streiff syndrome Cases 150 3197 Hereditary hyperekplexia Cases 150 3265 Humero-radial synostosis Cases Microcephalic osteodysplastic primordial dwarfism 150 2637 type II Cases 150 662 Yellow nail syndrome Cases 150 35069 Infantile neuroaxonal dystrophy Cases 150 28378 Tyrosinemia type 2 Cases 150 37748 Schnitzler syndrome Cases 150 188 Systemic capillary leak syndrome Cases 150 71274 Disseminated peritoneal leiomyomatosis Cases 150 52503 X-linked creatine transporter deficiency Cases Glycogen storage disease due to glucose-6150 79259 phosphatase deficiency type b Cases 254509 Iatrogenic botulism

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

18

ORPHA Number

Disease or Group of diseases

Number of cases

150 Cases 150 93682 Pediatric Castleman disease Cases 150 139411 Carney triad Cases 150 168816 Peritoneal cystic mesothelioma Cases 150 314777 Familial isolated pituitary adenoma Cases 150 284454 Acute zonal occult outer retinopathy Cases 148 135 CACH syndrome Cases 147 398166 Focal facial dermal dysplasia Cases 145 166113 Bazex syndrome Cases 143 113 Bazex-Dupré-Christol syndrome Cases 140 2576 MULIBREY nanism Cases 140 83450 Regional odontodysplasia Cases 140 79314 L-2-hydroxyglutaric aciduria Cases 140 90003 IgG4-related hepatopathy Cases Mendelian susceptibility to mycobacterial diseases 140 319552 due to complete IL12RB1 deficiency Cases 137 2290 Microvillus inclusion disease Cases Immune dysregulation-polyendocrinopathy136 37042 enteropathy-X-linked syndrome Cases 130 3400 Aorto-ventricular tunnel Cases 130 178307 Reticulate acropigmentation of Kitamura Cases 130 834 Free sialic acid storage disease Cases Leukoencephalopathy with brain stem and spinal 127 137898 cord involvement - high lactate Cases 125 650 LCAT deficiency Cases 123 1305 Feingold syndrome Cases 120 2343 Isolated cloverleaf skull syndrome Cases 120 51 Aicardi-Goutières syndrome Cases Hereditary motor and sensory neuropathy, 120 90117 Okinawa type Cases 120 100026 Gamma-heavy chain disease Cases 84142 Isaac syndrome

ORPHA Number

Disease or Group of diseases

Number of cases

120 Cases Combined hamartoma of the retina and retinal 120 440727 pigment epithelium Cases 117 3138 Ulnar-mammary syndrome Cases 117 398073 Prader-Willi-like syndrome Cases 115 48918 Focal myositis Cases 115 98967 Schnyder corneal dystrophy Cases 114 261494 Kleefstra syndrome Cases Postaxial polydactyly-anterior pituitary anomalies- 112 420584 facial dysmorphism syndrome Cases Hyperornithinemia-hyperammonemia111 415 homocitrullinuria syndrome Cases 110 245 Nager syndrome Cases Familial primary hypomagnesemia with 110 31043 hypercalciuria and nephrocalcinosis without severe Cases ocular involvement 106 86909 Myoclonic epilepsy of infancy Cases Hypomyelination-hypogonadotropic105 88637 hypogonadism-hypodontia syndrome Cases 105 221150 Pitt-Hopkins-like syndrome Cases 100 349 Fucosidosis Cases 100 800 Schwartz-Jampel syndrome Cases 100 45 Adenosine monophosphate deaminase deficiency Cases 100 833 Encephalopathy due to sulfite oxidase deficiency Cases 100 2053 Freeman-Sheldon syndrome Cases 100 2785 Osteopetrosis with renal tubular acidosis Cases 100 2414 Congenital pulmonary lymphangiectasia Cases 100 477 KID syndrome Cases 100 291 Fetal varicella syndrome Cases 100 2882 Sitosterolemia Cases 100 274 Bernard-Soulier syndrome Cases 100 869 Triple A syndrome Cases 100 981 Internal carotid agenesis Cases 391641 Feingold syndrome type 1

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

19

ORPHA Number

Disease or Group of diseases

100 Cases 100 Pallister-Hall syndrome Cases 100 Hypertrichosis lanuginosa congenita Cases 100 Frontometaphyseal dysplasia Cases 100 Osteopathia striata - cranial sclerosis Cases 100 Arthrogryposis - renal dysfunction - cholestasis Cases 100 Ochoa syndrome Cases 100 Haim-Munk syndrome Cases 100 Autosomal dominant Robinow syndrome Cases Immunodeficiency by defective expression of HLA 100 class 2 Cases 100 Mitochondrial trifunctional protein deficiency Cases 100 Fumaric aciduria Cases 100 Congenital intrinsic factor deficiency Cases 100 Sweet syndrome Cases 100 Congenital amegakaryocytic thrombocytopenia Cases 100 Rasmussen subacute encephalitis Cases Megalencephalic leukoencephalopathy with 100 subcortical cysts Cases 100 Autosomal agammaglobulinemia Cases 100 Tangier disease Cases Primary hypomagnesemia with secondary 100 hypocalcemia Cases 100 PHACE syndrome Cases 100 Aromatic L-amino acid decarboxylase deficiency Cases 100 Wagner disease Cases 100 Idiopathic acute eosinophilic pneumonia Cases 100 Rapid-onset dystonia-parkinsonism Cases Immunodeficiency due to selective anti100 polysaccharide antibody deficiency Cases 100 McLeod neuroacanthocytosis syndrome Cases

1507 Autosomal recessive Robinow syndrome 672 2222 1826 2780 2697 2704 2342 3107 572 746 24 332 3243 3319 1929 2478 33110 31150 30924 42775 35708 898 724 71517 70593 59306

Number of cases

ORPHA Number

Disease or Group of diseases

Number of cases

100 Cases 100 79409 Recessive dystrophic epidermolysis bullosa inversa Cases 100 77258 Trichorhinophalangeal syndrome type 1 and 3 Cases 100 75326 Retinal arterial tortuosity Cases 100 79086 Acquired generalized lipodystrophy Cases Monoclonal Ig light chain-associated Fanconi 100 91136 syndrome Cases 100 89937 Autosomal dominant hypophosphatemic rickets Cases 100 86813 Helicoid peripapillary chorioretinal degeneration Cases 100 94087 Cytophagic histiocytic panniculitis Cases 100 93686 Multicentric Castleman disease Cases 100 139380 Recessive hereditary methemoglobinemia type 2 Cases 100 99015 Spastic paraplegia type 2 Cases 100 221008 Rothmund-Thomson syndrome type 1 Cases 100 238769 1q44 microdeletion syndrome Cases 100 254478 Lichen planus pemphigoides Cases 100 140957 Autosomal dominant macrothrombocytopenia Cases 100 168569 H syndrome Cases 100 199241 Pulmonary capillary hemangiomatosis Cases 100 306741 Hemidystonia-hemiatrophy syndrome Cases 100 1293 Brachyolmia Cases 100 1310 Caffey disease Cases 100 1221 Cheilitis glandularis Cases 100 351 Galactosialidosis Cases 100 352723 Attenuated Chédiak-Higashi syndrome Cases 100 65748 Multiple self-healing squamous epithelioma Cases 100 502 Langer-Giedion syndrome Cases 100 79493 Brooke-Spiegler syndrome Cases 79403 Junctional epidermolysis bullosa - pyloric atresia

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

20

ORPHA Number

Disease or Group of diseases

261476 Monosomy Xp21 Autosomal dominant neovascular inflammatory vitreoretinopathy 71276 Silent sinus syndrome 293181 Malignant migrating partial seizures of infancy 329211

52368 Mohr-Tranebjaerg syndrome 1885 Isolated ectopia lentis 742

Prolidase deficiency Progressive non-infectious anterior vertebral 2062 fusion 276198 Spinocerebellar ataxia type 36 2473 McKusick-Kaufman syndrome

Number of cases

100 Cases 99 Cases 98 Cases 94 Cases 91 Cases 90 Cases 90 Cases 90 Cases 90 Cases 90 Cases

59

Allan-Herndon-Dudley syndrome

89 Cases

347

Frasier syndrome

88 Cases

2044 Floating-Harbor syndrome 96147 Kleefstra syndrome due to 9q34 microdeletion 3403 Uhl anomaly Glycogen storage disease due to LAMP-2 34587 deficiency 2635 Metatropic dysplasia 79133 Focal facial dermal dysplasia type I

87 Cases 86 Cases 84 Cases 84 Cases 81 Cases 81 Cases

98961 Reis-Bücklers corneal dystrophy 333 Farber disease

81 Cases

1935 Early myoclonic encephalopathy 526 Liddle syndrome

80 Cases

955

Acroosteolysis dominant type

80 Cases

709

Peters plus syndrome

80 Cases

382

Guanidinoacetate methyltransferase deficiency

80 Cases

3342 Arterial tortuosity syndrome 901 Wells syndrome 49

Penile agenesis Thiamine-responsive megaloblastic anemia 49827 syndrome 79315 D-2-hydroxyglutaric aciduria 97229 Riboflavin transporter deficiency Autosomal recessive early-onset inflammatory 238569 bowel disease 231401 Alpha-thalassemia-myelodysplastic syndrome 950 Acrodysostosis 2396 Encephalocraniocutaneous lipomatosis 1393 Cerebro-costo-mandibular syndrome 79230 Hemochromatosis type 2 209981 IRIDA syndrome 622

Homocystinuria without methylmalonic aciduria Mutilating palmoplantar keratoderma with 659 periorificial keratotic plaques 2196 Familial primary hypomagnesemia with

80 Cases 80 Cases

80 Cases 80 Cases 80 Cases

ORPHA Number

Disease or Group of diseases

hypercalciuria and nephrocalcinosis with severe ocular involvement 2671 Neu-Laxova syndrome 1830 Schimke immuno-osseous dysplasia

Number of cases

72 Cases 71 Cases

1442 Ring chromosome 18 760 Purine nucleoside phosphorylase deficiency

70 Cases

2123 Diffuse neonatal hemangiomatosis 2006 Median cleft lip/mandibule

70 Cases

2484 Melnick-Needles syndrome 756 Pseudohypoaldosteronism type 1

70 Cases

65759 Carpenter syndrome 46489 Bullous systemic lupus erythematosus

70 Cases

79293 Familial LCAT deficiency 79257 GM1 gangliosidosis type 3

70 Cases

160148 Cap polyposis 2268 ICF syndrome

67 Cases

32 Glutathione synthetase deficiency 2333 Kenny-Caffey syndrome 51636 WHIM syndrome

65 Cases

90354 Brittle cornea syndrome Hereditary hyperferritinemia with congenital 163 cataracts 3242 Renpenning syndrome 75392 Ehlers-Danlos syndrome, periodontitis type

65 Cases

70 Cases 70 Cases 70 Cases 70 Cases

70 Cases Autosomal dominant mendelian susceptibility to 319581 mycobacterial diseases due to partial IFNgammaR1 70 Cases deficiency 404546 DITRA 70 Cases 357043 Amyotrophic lateral sclerosis type 4 70 Cases Congenital adrenal hyperplasia due to 3-beta90791 68 Cases hydroxysteroid dehydrogenase deficiency 98975 Congenital hereditary endothelial dystrophy type I 68 Cases 2554 Ear-patella-short stature syndrome 67 Cases 66 Cases 65 Cases 65 Cases

64 Cases 64 Cases

80 Cases

62 Cases 2855 Perrault syndrome 61 Cases 3051 Intellectual disability - sparse hair - brachydactyly 61 Cases 699 Pearson syndrome 60 Cases

80 Cases

239

Dyggve-Melchior-Clausen disease

60 Cases

677

Pancreatoblastoma

60 Cases

381

Griscelli disease

60 Cases

80 Cases 80 Cases

80 Cases 80 Cases 77 Cases 75 Cases 74 Cases 74 Cases

969 Acromicric dysplasia 1270 Bowen-Conradi syndrome 1667 Wolcott-Rallison syndrome

60 Cases

139

60 Cases

CHILD syndrome

60 Cases 60 Cases

73 Cases

2065 Galloway-Mowat syndrome 2462 Shprintzen-Goldberg syndrome

60 Cases

73 Cases

708

Peters anomaly

60 Cases

72 Cases

159

Carnitine-acylcarnitine translocase deficiency

60 Cases

60 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

21

ORPHA Number

Disease or Group of diseases

Number of cases

3338 Toriello-Carey syndrome 3411 Double uterus - hemivagina - renal agenesis

60 Cases

2221 Acquired hypertrichosis lanuginosa 721 Gray platelet syndrome

60 Cases

52530 Pseudo-von Willebrand disease 63455 Paraneoplastic pemphigus

60 Cases

Vitamin B12-responsive methylmalonic acidemia type cblA Mandibulofacial dysostosis-microcephaly 79113 syndrome 90349 Autosomal recessive cutis laxa type 1 99803 Haddad syndrome 79310

158029 Sea-blue histiocytosis 300493 Sagliker syndrome 773

Refsum disease

2332 KBG syndrome 79320 ALG6-CDG

60 Cases 60 Cases 60 Cases 60 Cases 60 Cases 60 Cases 60 Cases 60 Cases 60 Cases 60 Cases 59 Cases 58 Cases

293642 Blepharophimosis-intellectual disability syndrome 58 Cases 88644 Autosomal recessive ataxia, Beauce type 57 Cases Autosomal recessive severe congenital 331176 57 Cases neutropenia due to G6PC3 deficiency 46 Adenylosuccinate lyase deficiency 56 Cases 71 Chylomicron retention disease 55 Cases 2556 Microphthalmia with linear skin defects syndrome 55 Cases 826 Sporotrichosis 55 Cases 57782 Mazabraud syndrome 54 Cases 83628 PELVIS syndrome Autosomal recessive spastic ataxia with 314603 leukoencephalopathy 79099 Interstitial granulomatous dermatitis with arthritis 251515 Distal arthrogryposis type 10

54 Cases 54 Cases 53 Cases

53 Cases 178509 Perry syndrome 53 Cases 398088 Hereditary cryohydrocytosis with normal stomatin 53 Cases 3473 Zimmermann-Laband syndrome 52 Cases 251671 Angiocentric glioma 98767 Spinocerebellar ataxia type 11 585

Multiple sulfatase deficiency

868

52 Cases 51 Cases 50 Cases

Triose phosphate-isomerase deficiency 1414 Cholestasis-lymphedema syndrome 2801 Juvenile Paget disease

50 Cases

3111 Rotor syndrome 574 Monosomy 21

50 Cases

808

Seckel syndrome

50 Cases

871

Familial progressive cardiac conduction defect

50 Cases

897

Waardenburg-Shah syndrome

50 Cases

1444 Ring chromosome 20 40 Acromesomelic dysplasia, Maroteaux type

50 Cases 50 Cases 50 Cases

50 Cases 50 Cases

ORPHA Number

Disease or Group of diseases

Number of cases

156 Carnitine palmitoyl transferase 1A deficiency 1253 Ascher syndrome 127 Borjeson-Forssman-Lehmann syndrome

50 Cases

1297 Branchio-oculo-facial syndrome 1125 Ocular motor apraxia, Cogan type

50 Cases

1425 Desbuquois syndrome 165 Neutral lipid storage disease

50 Cases

2078 Geroderma osteodysplastica 2143 Donnai-Barrow syndrome

50 Cases

2136 Hennekam syndrome 1997 Blepharo-cheilo-odontic syndrome

50 Cases

2028 Juvenile hyaline fibromatosis 2632 Langer mesomelic dysplasia

50 Cases

2461 Marden-Walker syndrome 2407 LOC syndrome

50 Cases

2896 Pitt-Hopkins syndrome 2805 Partial pancreatic agenesis

50 Cases

50 Cases 50 Cases

50 Cases 1118 Fibular aplasia - ectrodactyly 50 Cases 1573 Hypotrichosis with juvenile macular degeneration 50 Cases 1440 Ring chromosome 14 50 Cases

Hemolytic anemia due to glucophosphate 712 isomerase deficiency 851 Paris-Trousseau thrombocytopenia 3231 Deafness-onychodystrophy syndrome

50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases

3253 Zlotogora-Ogur syndrome 361 Familial glucocorticoid deficiency

50 Cases

1902 Ehrlichiosis 33111 Granulomatous slack skin

50 Cases

29822 Spontaneous periodic hypothermia 71518 Benign paroxysmal torticollis of infancy

50 Cases

59315 Rhombencephalosynapsis 53540 Goldmann-Favre syndrome

50 Cases

79500 DOORS syndrome 79143 Isolated congenital anonychia

50 Cases

79256 GM1 gangliosidosis type 2 75382 Oguchi disease

50 Cases

91496 Snowflake vitreoretinal degeneration 90342 Xeroderma pigmentosum variant

50 Cases

90348 Autosomal dominant cutis laxa 86816 Congenital analbuminemia

50 Cases

Cystic leukoencephalopathy without 85136 megalencephaly 85212 Fetal Gaucher disease 98811 Paroxysmal exertion-induced dyskinesia

50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases 50 Cases

Glycogen storage disease due to phosphoglycerate 50 Cases mutase deficiency 93600 Primary hyperoxaluria type 3 50 Cases 97234

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

22

ORPHA Number

Disease or Group of diseases

137888 Auriculocondylar syndrome 101150 Autosomal recessive dopa-responsive dystonia

Number of cases

50 Cases 50 Cases

102069 Hepatic amyloidosis with intrahepatic cholestasis 50 Cases 100012 Lissencephaly with cerebellar hypoplasia type B 50 Cases 99872 Hashimoto-Pritzker syndrome 50 Cases

ORPHA Number

Disease or Group of diseases

1052 Mosaic variegated aneuploidy syndrome 254351 Distal 7q11.23 microdeletion syndrome 398156 Oculoauriculofrontonasal syndrome 2301 Congenital short bowel syndrome 2771 Bruck syndrome

Number of cases

41 Cases 41 Cases 41 Cases 41 Cases 40 Cases

217385 17p13.3 microduplication syndrome 221046 Poikiloderma with neutropenia

50 Cases

157846 Neuroferritinopathy 171929 Trisomy 10p

50 Cases

208513 Spinocerebellar ataxia type 29 206583 Adult polyglucosan body disease

50 Cases

Tetrasomy X 40 Cases Congenital cataract - hypertrophic cardiomyopathy 1369 40 Cases - mitochondrial myopathy 2971 Peroxisomal acyl-CoA oxidase deficiency 40 Cases 1745 Distal trisomy 6p 40 Cases

50 Cases

40 Cases

300512 Onychomatricoma Xeroderma pigmentosum complementation group 276255 C 284448 CLIPPERS Multicentric osteolysis-nodulosis-arthropathy 371428 spectrum 404507 Chondromyxoid fibroma 352636 Phalangeal microgeodic syndrome

50 Cases

79147 Familial reactive perforating collagenosis Keratoderma hereditarium mutilans with 79395 ichthyosis 1873 Jalili syndrome 54251 Corticosteroid-sensitive aseptic abscess syndrome

50 Cases

50 Cases 50 Cases

50 Cases 50 Cases 50 Cases 50 Cases 50 Cases

50 Cases 49 Cases

49 Cases Mendelian susceptibility to mycobacterial diseases 319558 49 Cases due to complete IL12B deficiency 255229 Navajo neurohepatopathy 49 Cases 3447 Weaver syndrome 48 Cases

9

1742 Trisomy 5p 1699 Trisomy 12p Congenital generalized hypertrichosis, Ambras 1023 type 1923 Methimazole embryofetopathy 859 Transcobalamin deficiency

40 Cases 40 Cases 40 Cases 40 Cases

1517 Hypertrichotic osteochondrodysplasia, Cantu type 40 Cases 2273 Ichthyosis follicularis - alopecia - photophobia 40 Cases 2470 Matthew-Wood syndrome 40 Cases 2457 Mandibuloacral dysplasia 2962 De Barsy syndrome Epidermolysis bullosa simplex with muscular dystrophy Autosomal dominant hypohidrotic ectodermal 1810 dysplasia 51188 Ethylmalonic encephalopathy 79134 DEND syndrome 257

40 Cases 40 Cases 40 Cases 40 Cases 40 Cases 40 Cases

2897 Pityriasis rubra pilaris Rapid-onset childhood obesity - hypothalamic 293987 dysfunction - hypoventilation - autonomic dysregulation syndrome 989 Hypoglossia-hypodactyly syndrome 1509 Coxopodopatellar syndrome

48 Cases

90350 Autosomal recessive cutis laxa type 2 96102 Distal trisomy 10q

40 Cases

48 Cases

96148 Distal monosomy 10q 95159 Hepatoerythropoietic porphyria

47 Cases

210548 Macrocephaly-autism syndrome 228384 5q14.3 microdeletion syndrome

40 Cases

216828 Osteogenesis imperfecta type 5 250994 1q21.1 microduplication syndrome

47 Cases

210122 Congenital alveolar capillary dysplasia 314422 Ameloblastic carcinoma

40 Cases

263534 Acral peeling skin syndrome 280785 Bullous diffuse cutaneous mastocytosis

40 Cases

798

Schinzel-Giedion syndrome

47 Cases 46 Cases 46 Cases

86788 X-linked severe congenital neutropenia 99749 Kostmann syndrome

45 Cases

209932 Cone dystrophy with supernormal rod response 279947 Postorgasmic illness syndrome

45 Cases

284984 Aneurysm-osteoarthritis syndrome Mitochondrial DNA depletion syndrome, 254875 myopathic form 84064 Syndromic diarrhea Seborrhea-like dermatitis with psoriasiform 168606 elements Dopa-responsive dystonia due to sepiapterin 70594 reductase deficiency

45 Cases

45 Cases 45 Cases

45 Cases 44 Cases 44 Cases 43 Cases

40 Cases 40 Cases 40 Cases 40 Cases 40 Cases

40 Cases 280651 Acrodysostosis with multiple hormone resistance 40 Cases 281190 Congenital reticular ichthyosiform erythroderma 40 Cases 411777 Generalized eruptive keratoacanthoma 40 Cases 1515 Cranioectodermal dysplasia 1647 Oculocerebrocutaneous syndrome 2067 GAPO syndrome 55654 Hypotrichosis simplex Autosomal dominant rhegmatogenous retinal 209867 detachment 314621 Duplication of the pituitary gland

39 Cases 38 Cases 38 Cases 38 Cases 38 Cases 38 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

23

ORPHA Number

Disease or Group of diseases

Number of cases

ORPHA Number

Disease or Group of diseases

1993 Pai syndrome 3208 Isolated succinate-CoQ reductase deficiency

37 Cases 37 Cases

141096 Supernumerary nostril 293843 3MC syndrome

79406 Late-onset junctional epidermolysis bullosa 1766 Dysequilibrium syndrome

37 Cases

314373

1855 Spondyloenchondrodysplasia 98955 Lisch epithelial corneal dystrophy Hereditary North American Indian childhood 168583 cirrhosis 300573 Polymicrogyria due to TUBB2B mutation Benign infantile focal epilepsy with midline spikes 166308 and wave during sleep 446 Neonatal hemochromatosis 2040 Congenital bronchobiliary fistula

36 Cases

Hereditary sensory and autonomic neuropathy type 2 53721 Cobb syndrome 96125 Distal monosomy 6p 970

100024 Mu-heavy chain disease 293621 X-linked endothelial corneal dystrophy

37 Cases 36 Cases 36 Cases 36 Cases 36 Cases 35 Cases 35 Cases 35 Cases 35 Cases 35 Cases

Chronic diarrhea due to guanylate cyclase 2C overactivity Autosomal recessive ataxia due to ubiquinone 139485 deficiency Lower motor neuron syndrome with late-adult 276435 onset 96173 Ring chromosome 9 Glycogen storage disease due to muscle 371 phosphofructokinase deficiency 246 Postaxial acrofacial dysostosis 29 Mevalonic aciduria 1065 2746 715

35 Cases

1752

35 Cases

957

Aniridia-cerebellar ataxia-intellectual disability syndrome Opsismodysplasia Glycogen storage disease due to muscle phosphorylase kinase deficiency Trisomy 8q

Number of cases

32 Cases 32 Cases 32 Cases 31 Cases 31 Cases 31 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases

Acropectorovertebral dysplasia 2615 Nakajo-Nishimura syndrome 1229 Congenital intrauterine infection-like syndrome

30 Cases

1225 Baller-Gerold syndrome 1662 Restrictive dermopathy

30 Cases

34 Cases 69126 Pyogenic arthritis - pyoderma gangrenosum - acne 34 Cases 217031 Obesity due to MC3R deficiency 34 Cases 2874 Phakomatosis pigmentokeratotica 34 Cases

1545 Crisponi syndrome 1525 Cranio-osteoarthropathy

30 Cases

1427 Otospondylomegaepiphyseal dysplasia 2036 Scalp-ear-nipple syndrome

30 Cases

363528 Intellectual disability-strabismus syndrome Short stature-optic atrophy-Pelger-Huët anomaly 391677 syndrome 398097 Neonatal antiphospholipid syndrome 93269 Short rib-polydactyly syndrome, Majewski type

2763 Osteocraniostenosis 2733 Omodysplasia

30 Cases

36

Acrocallosal syndrome

34 Cases

1437 Ring chromosome 1 83 Antley-Bixler syndrome

34 Cases

1532 Gómez-López-Hernández syndrome 943 Malonic aciduria

34 Cases

34 Cases

34 Cases

30 Cases 30 Cases 30 Cases 30 Cases 30 Cases

2406 Locked-in syndrome 1388 Catel-Manzke syndrome

33 Cases

2783 Autosomal dominant osteopetrosis type 1 561 Marshall-Smith syndrome

33 Cases

30 Cases Blepharophimosis-intellectual disability syndrome, 2728 30 Cases Ohdo type Microcephalic osteodysplastic primordial dwarfism 2636 30 Cases types I and III 2399 Nasopalpebral lipoma - coloboma - telecanthus 30 Cases 3005 Pyle disease 30 Cases

33 Cases

30 Cases

3102 Richieri Costa-Pereira syndrome 2170 Methylcobalamin deficiency type cblG

33 Cases

2834 Wrinkly skin syndrome 669 Otopalatodigital syndrome 3266 Humero-radio-ulnar synostosis 3258 Cenani-Lenz syndrome

30 Cases

3352 Tricho-dento-osseous syndrome 2995 Baraitser-Winter syndrome

30 Cases

3448 Weaver-Williams syndrome 3464 Woodhouse-Sakati syndrome

30 Cases

32 Cases

30 Cases 2849 Perlman syndrome 30 Cases 35705 Neurometabolic disorder due to serine deficiency 30 Cases 66628 Obesity due to congenital leptin deficiency 30 Cases

32 Cases

79411 Transient bullous dermolysis of the newborn

30 Cases

832

34 Cases 34 Cases 34 Cases 33 Cases

33 Cases

Succinyl-CoA:3-ketoacid CoA transferase deficiency 33 Cases

3322 Hoyeraal-Hreidarsson syndrome 33 Cases 2795 Polycystic ovaries - urethral sphincter dysfunction 33 Cases 123 Björnstad syndrome 33 Cases 225123 Hemochromatosis type 3 3163 SHORT syndrome

33 Cases

3255 Filippi syndrome 35664 ALDH18A1-related De Barsy syndrome 67039 Segmental odontomaxillary dysplasia

32 Cases

32 Cases

30 Cases 30 Cases 30 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

24

ORPHA Number

Disease or Group of diseases

Number of cases

ORPHA Number

79456 Diffuse cutaneous mastocytosis 79292 Fish-eye disease

30 Cases

228174

79155 Encephalopathy due to hydroxykynureninuria 79157 2-methylbutyryl-CoA dehydrogenase deficiency

30 Cases

Anophthalmia/microphthalmia - esophageal atresia 77301 Monosomy 9q22.3 91481 Ring dermoid of cornea 77298

93315 93346 88924 90045 85164 85278

Spondylometaphyseal dysplasia, 'corner fracture' type Spondyloepimetaphyseal dysplasia congenita, Strudwick type Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis Hereditary folate malabsorption Camptodactyly - tall stature - scoliosis - hearing loss Christianson syndrome

30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases

85202 Keutel syndrome 98764 Spinocerebellar ataxia type 27

30 Cases

97297 Bohring-Opitz syndrome 93940 Laryngo-tracheo-esophageal cleft type 3

30 Cases

140933 Linear atrophoderma of Moulin 98970 Fleck corneal dystrophy

30 Cases

Xeroderma pigmentosum-Cockayne syndrome 220295 complex Carnitine palmitoyl transferase II deficiency, 228305 severe infantile form 228116 Hughes-Stovin syndrome 228236 Linear focal dermal elastosis

30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases 30 Cases

238446 15q11q13 microduplication syndrome 163746 Neurologic Waardenburg-Shah syndrome

30 Cases

141163 Glossopalatine ankylosis Severe neonatal-onset encephalopathy with 209370 microcephaly 209943 IRVAN syndrome 294049 Reunion Island's Larsen syndrome

30 Cases

275523 Dianzani autoimmune lymphoproliferative disease Xeroderma pigmentosum complementation group 276258 D 91396 Isolated cryptophthalmia 1943 Infant epilepsy with migrant focal crisis

30 Cases

1314 Symmetrical thalamic calcifications 2753 Orofaciodigital syndrome type 4 Leukoencephalopathy with bilateral anterior temporal lobe cysts 2220 Hypertrichosis cubiti - short stature 3459 Wilson-Turner syndrome

139444

50814 Craniolenticulosutural dysplasia

30 Cases

Disease or Group of diseases

Autosomal dominant Charcot-Marie-Tooth disease type 2N Gastric adenocarcinoma and proximal polyposis of 314022 the stomach 329466 Autosomal dominant focal dystonia, DYT25 Familial episodic pain syndrome with 391392 predominantly lower limb involvement 466 Fatal familial insomnia 1040 Metaphyseal anadysplasia

Number of cases

28 Cases 28 Cases 28 Cases 28 Cases 27 Cases 27 Cases

2169 Methylcobalamin deficiency type cblE Noonan syndrome-like disorder with loose anagen 2701 hair 2623 Geleophysic dysplasia 69085 Limb-mammary syndrome

27 Cases

99812 LIG4 syndrome 251287 Benign concentric annular macular dystrophy

27 Cases

Hereditary diffuse leukoencephalopathy with 313808 axonal spheroids and pigmented glia X-linked central congenital hypothyroidism with 329235 late-onset testicular enlargement 1262 Böök syndrome 40366 Acitretin/etretinate embryopathy 98771 Spinocerebellar ataxia type 18 Multiple congenital anomalies due to 14q32.2 254519 maternally expressed gene defect Motor developmental delay due to 14q32.2 254516 paternally expressed gene defect Syndactyly - camptodactyly and clinodactyly of 357332 fifth fingers - bifid toes 7 3C syndrome Palmoplantar keratoderma-spastic paralysis 2201 syndrome 1955 Spinocerebellar ataxia type 34 2499 Metachondromatosis

27 Cases 27 Cases 27 Cases 27 Cases 27 Cases 27 Cases 26 Cases 26 Cases 26 Cases 26 Cases 26 Cases 26 Cases 25 Cases 25 Cases 25 Cases 25 Cases

3455 Wiedemann-Rautenstrauch syndrome 3472 Yunis-Varon syndrome

25 Cases

39041 Omenn syndrome 50944 Schöpf-Schulz-Passarge syndrome

25 Cases

54028 Plummer-Vinson syndrome 56305 Atelosteogenesis type III

25 Cases

56304 Atelosteogenesis type II Hepatic veno-occlusive disease 79124 immunodeficiency 93109 Congenital megacalycosis 85173 IMAGe syndrome

25 Cases

28 Cases

25 Cases 251019 2q32q33 microdeletion syndrome 25 Cases 166286 Porokeratotic eccrine ostial and dermal duct nevus 25 Cases

28 Cases

314597 Chudley-McCullough syndrome 268249 Mycophenolate mofetil embryopathy

25 Cases

30 Cases 30 Cases 30 Cases

30 Cases 30 Cases 29 Cases 29 Cases 29 Cases 29 Cases

28 Cases

25 Cases 25 Cases 25 Cases

25 Cases 25 Cases

25 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

25

ORPHA Number

Disease or Group of diseases

281122 Self-healing collodion baby Autosomal dominant childhood-onset proximal 363454 spinal muscular atrophy with contractures 1715 Trisomy 18p 1234 Bartsocas-Papas syndrome 1186 Infantile onset spinocerebellar ataxia 1361 Carnosinemia

Number of cases

25 Cases 25 Cases 25 Cases 24 Cases 24 Cases 24 Cases

3275 Spondylocarpotarsal synostosis Distal myopathy with early respiratory muscle 34521 involvement 98972 Central cloudy dystrophy of Francois Hyperphosphatasia-intellectual disability 247262 syndrome 171607 X-linked spastic paraplegia type 34 Hypercholesterolemia due to cholesterol 7alpha209902 hydroxylase deficiency Pyogenic bacterial infections due to MyD88 183713 deficiency 300525 Pseudohypoaldosteronism type 2D Autosomal dominant cerebellar ataxia, deafness 314404 and narcolepsy Familial cutaneous telangiectasia and 313846 oropharyngeal predisposition cancer syndrome PURA-related severe neonatal hypotonia-seizures438216 encephalopathy syndrome due to a point mutation 1617 2q24 microdeletion syndrome 52022 Potocki-Shaffer syndrome

24 Cases

93329 Autosomal recessive omodysplasia 101028 Transaldolase deficiency 238475 Familial hypercholanemia

23 Cases

261652 Kleefstra syndrome due to a point mutation 411493 Pontocerebellar hypoplasia type 10

23 Cases

24 Cases 24 Cases 24 Cases 24 Cases 24 Cases 24 Cases 24 Cases 24 Cases 24 Cases 24 Cases 23 Cases 23 Cases 23 Cases 23 Cases 23 Cases

Combined immunodeficiency due to LRBA 23 Cases deficiency 2670 Pierson syndrome 22 Cases 2953 Ehlers-Danlos syndrome, musculocontractural type 22 Cases

445018

71271 Split hand - split foot - deafness Autosomal dominant deafness-onychodystrophy 79499 syndrome Familial thoracic aortic aneurysm and aortic 91387 dissection 85201 Genitopatellar syndrome 85203 Acro-pectoral syndrome

22 Cases

93953 Familial thyroglossal duct cyst 228423 Monocytopenia with susceptibility to infections

22 Cases

Generalized congenital lipodystrophy with myopathy 163690 Hypotonia-cystinuria syndrome 209908 Childhood apraxia of speech 228429

314718 Lethal arteriopathy syndrome due to fibulin-4

22 Cases 22 Cases 22 Cases 22 Cases 22 Cases 22 Cases 22 Cases 22 Cases

ORPHA Number

Disease or Group of diseases

deficiency Developmental delay with autism spectrum 329195 disorder and gait instability 269229 Pontine tegmental cap dysplasia Xeroderma pigmentosum complementation group 276264 F Childhood-onset autosomal recessive myopathy 363677 with external ophthalmoplegia 398173 Focal facial dermal dysplasia type II 431255 Scapuloperoneal spinal muscular atrophy 445038 3-methylglutaconic aciduria type 7 2588 Myhre syndrome 1578 Dehydratase deficiency 230 Dopamine beta-hydroxylase deficiency 69082 Odonto-tricho-ungual-digito-palmar syndrome Autosomal dominant intermediate Charcot-Marie93114 Tooth disease type E Nephrogenic syndrome of inappropriate 93606 antidiuresis 217330 Hyperuricemia - anemia - renal failure 168593 Sudden infant death - dysgenesis of the testes Isolated autosomal dominant hypomagnesemia, 199326 Glaudemans type Autosomal dominant focal non-epidermolytic 402003 palmoplantar keratoderma with plantar blistering Fatal multiple mitochondrial dysfunction 401869 syndrome type 1 Familial episodic pain syndrome with 391389 predominantly upper body involvement 398189 Focal facial dermal dysplasia type IV 30 Hereditary orotic aciduria

Number of cases

22 Cases 22 Cases 22 Cases 22 Cases 22 Cases 22 Cases 22 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 21 Cases 20 Cases

3137 Alpha-N-acetylgalactosaminidase deficiency 1358 Carey-Fineman-Ziter syndrome

20 Cases

971

Acrorenal syndrome Hypertrichosis-acromegaloid facial appearance 966 syndrome 965 Acromegaloid facial appearance syndrome 1807 Focal facial dermal dysplasia type III

20 Cases

1519 Hypertelorism, Teebi type 1513 Craniodiaphyseal dysplasia

20 Cases

1493 Vici syndrome 1387 Cataract - intellectual disability - hypogonadism

20 Cases

1466 COFS syndrome 455 Superficial epidermolytic ichthyosis

20 Cases

2755 Orofaciodigital syndrome type 8 Laryngeal abductor paralysis - intellectual 2375 disability 2363 Lacrimoauriculodentodigital syndrome 3021 RAPADILINO syndrome

20 Cases

20 Cases

20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases

20 Cases 20 Cases 20 Cases

22 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

26

ORPHA Number

Disease or Group of diseases

Number of cases

Blepharophimosis-intellectual disability syndrome, 20 Cases SBBYS type 2847 Pericardial and diaphragmatic defect 20 Cases 3226 Deafness - lymphedema - leukemia 20 Cases 3047

3387 Isolated anterior cervical hypertrichosis 1134 Arrhinia

20 Cases 20 Cases

2394 Pyruvate dehydrogenase E3 deficiency 198 Occipital horn syndrome

20 Cases

33445 Neuroectodermal melanolysosomal disease 26137 Juvenile temporal arteritis

20 Cases

91 Aromatase deficiency 69084 Pure hair and nail ectodermal dysplasia 67046 3-methylglutaconic aciduria type 1

20 Cases

69723 Tyrosinemia type 3 65283 Timothy syndrome

20 Cases

Radio-ulnar synostosis - amegakaryocytic thrombocytopenia Bleeding diathesis due to a collagen receptor 73271 defect 63442 Angel-shaped phalango-epiphyseal dysplasia 83616 Rubella panencephalitis 71289

20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases

79319 MPI-CDG 79154 2-aminoadipic 2-oxoadipic aciduria

20 Cases

79084 Familial partial lipodystrophy, Köbberling type Channelopathy-associated congenital insensitivity 88642 to pain 86797 Atypical lichen myxedematosus 88628 Posterior column ataxia - retinitis pigmentosa

20 Cases

86919 Keratosis palmaris et plantaris - clinodactyly 85192 Calvarial doughnut lesions - bone fragility

20 Cases

20 Cases

20 Cases 20 Cases 20 Cases

20 Cases Alpha-thalassemia-intellectual disability syndrome 98791 20 Cases linked to chromosome 16 98773 Spinocerebellar ataxia type 21 20 Cases 98768 Spinocerebellar ataxia type 13 20 Cases 97232 Fingerprint body myopathy 93941 Laryngo-tracheo-esophageal cleft type 4

20 Cases 20 Cases

139455 Autosomal recessive bestrophinopathy 137678 Czech dysplasia, metatarsal type

20 Cases

101110 Spinocerebellar ataxia type 20 100976 Bathing suit ichthyosis

20 Cases

20 Cases 20 Cases

Autosomal dominant Charcot-Marie-Tooth disease 20 Cases type 2M 228247 Acquired pseudoxanthoma elasticum 20 Cases 247522 Primary ciliary dyskinesia - retinitis pigmentosa 20 Cases 228179

Localized junctional epidermolysis bullosa, nonHerlitz type 251028 2q33.1 microdeletion syndrome 140966 Palmoplantar keratoderma, Nagashima type 251393

20 Cases 20 Cases 20 Cases

ORPHA Number

Disease or Group of diseases

Number of cases

178364 Syndromic microphthalmia type 5 209905 Brain-lung-thyroid syndrome

20 Cases

Cirrhosis-dystonia-polycythemiahypermanganesemia syndrome 352328 MEGDEL syndrome 261243 16p13.11 microduplication syndrome 309854

RAS-associated autoimmune leukoproliferative 268114 disease 280779 Cutaneous collagenous vasculopathy 289863 Atypical glycine encephalopathy Mitochondrial DNA depletion syndrome, 369897 encephalomyopathic form with variable craniofacial anomalies 420179 Malan overgrowth syndrome 3339 Toriello-Lacassie-Droste syndrome

20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases 20 Cases

19 Cases 1541 Craniosynostosis, Boston type 19 Cases Hereditary myopathy with lactic acidosis due to 43115 19 Cases ISCU deficiency 75857 6q terminal deletion syndrome 19 Cases Hereditary inclusion body myopathy - joint 79091 19 Cases contractures - ophthalmoplegia 89838 KRT14-related epidermolysis bullosa simplex 19 Cases Hypomyelination with atrophy of basal ganglia and 139441 19 Cases cerebellum 139447 Progressive cavitating leukoencephalopathy 19 Cases 228410 Polyvalvular heart disease syndrome 19 Cases 251046 6p22 microdeletion syndrome 178487 Adult intestinal botulism Polyneuropathy - hearing loss - ataxia - retinitis pigmentosa - cataract 293812 Fixed pigmented erythema Congenital muscular dystrophy due to 280671 phosphatidylcholine biosynthesis defect 401973 MEND syndrome 363558 New-onset refractory status epilepticus 171848

2353 Schilbach-Rott syndrome 2460 Van den Ende-Gupta syndrome Autosomal dominant primary hypomagnesemia 34528 with hypocalciuria 88630 Terminal osseous dysplasia - pigmentary defects Spondylometaphyseal dysplasia - cone-rod 85167 dystrophy Carnitine palmitoyl transferase II deficiency, 228308 neonatal form 228402 2q23.1 microdeletion syndrome 300319 Charcot-Marie-Tooth disease type 2P 324588 Familial dyskinesia and facial myokymia 397596 Activated PIK3-delta syndrome Methylmalonic acidemia with homocystinuria, 369962 type cblX

19 Cases 19 Cases 19 Cases 19 Cases 19 Cases 19 Cases 19 Cases 18 Cases 18 Cases 18 Cases 18 Cases 18 Cases 18 Cases 18 Cases 18 Cases 18 Cases 18 Cases 18 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

27

ORPHA Number

Disease or Group of diseases

Number of cases

370046 Didymosis aplasticosebacea 363417 Temtamy preaxial brachydactyly syndrome

18 Cases

2318 Joubert syndrome with oculorenal defect 560 Marshall syndrome

17 Cases

1325 Camptodactyly - taurinuria 1954 Congenital lethal erythroderma

17 Cases

1908 Aminopterin/methotrexate embryofetopathy 69744 Circumscribed palmoplantar hypokeratosis

17 Cases

18 Cases 17 Cases

ORPHA Number

Disease or Group of diseases

Number of cases

2731 Taurodontia - absent teeth - sparse hair 3097 Meacham syndrome

15 Cases

3405 Umbilical cord ulceration - intestinal atresia 3439 Von Voss-Cherstvoy syndrome

15 Cases

15 Cases 15 Cases

231573 Congenital erosive and vesicular dermatosis 163696 Action myoclonus-renal failure syndrome

17 Cases

300530 Pseudohypoaldosteronism type 2E 324381 Hereditary inclusion body myopathy type 4

17 Cases

Congenital membranous nephropathy due to 69063 maternal anti-neutral endopeptidase 15 Cases alloimmunization Immunodeficiency due to interleukin-1 receptor70592 15 Cases associated kinase-4 deficiency Methylmalonic acidemia with homocystinuria type 79284 15 Cases cblF 79327 ALG1-CDG 15 Cases Scleromyxedema without monoclonal 90400 15 Cases gammopathy 88620 Isolated congenital anosmia 15 Cases 103908 Congenital sodium diarrhea 15 Cases

17 Cases

221043

Methylmalonic acidemia with homocystinuria, 79283 type cblD 93282 Spondyloepimetaphyseal dysplasia, PAPSS2 type 99844 Leukocyte adhesion deficiency type III

Autoimmune lymphoproliferative syndrome due 436159 to CTLA4 haploinsuffiency Chronic atrial and intestinal dysrhythmia 435988 syndrome 99853 Ovarioleukodystrophy 1195 Congenital atransferrinemia 2102 GTP cyclohydrolase I deficiency 1438 Ring chromosome 10 920

17 Cases 17 Cases 17 Cases 17 Cases 17 Cases 17 Cases

16 Cases

Hereditary sclerosing poikiloderma with tendon and pulmonary involvement 140944 CLOVE syndrome Congenital muscular dystrophy due to LMNA 157973 mutation 171680 Lissencephaly due to TUBA1A mutation 314432 Spigelian hernia-cryptorchidism syndrome

16 Cases

314647

17 Cases 17 Cases 17 Cases

16 Cases

Ablepharon macrostomia syndrome

16 Cases 1974 Autosomal recessive facio-digito-genital syndrome 16 Cases 2752 Orofaciodigital syndrome type 3 16 Cases Glycogen storage disease due to hepatic glycogen 2089 16 Cases synthase deficiency 2538 Microgastria - limb reduction defect 16 Cases 33067 Metaphyseal chondrodysplasia, Jansen type 16 Cases Obesity due to prohormone convertase I 71528 deficiency 52994 Orbital leiomyoma 85198 Dysspondyloenchondromatosis 93972 Juberg-Marsidi syndrome 99901 Acyl-CoA dehydrogenase 9 deficiency

16 Cases 16 Cases 16 Cases 16 Cases

16 Cases 238455 Infantile dystonia-parkinsonism 16 Cases Hypoplastic pancreas-intestinal atresia-hypoplastic 293864 16 Cases gallbalder syndrome Intestinal obstruction in the newborn due to 314376 16 Cases guanylate cyclase 2C deficiency 314566 Primary progressive apraxia of speech 16 Cases 319171 Distal 17p13.1 microdeletion syndrome 16 Cases 279943 Hereditary neutrophilia Congenital sideroblastic anemia-B-cell 369861 immunodeficiency-periodic fever-developmental delay syndrome 2721 Odonto-onycho-dermal dysplasia

16 Cases 16 Cases 15 Cases

15 Cases 15 Cases 15 Cases 15 Cases 15 Cases

Non-progressive cerebellar ataxia with intellectual 15 Cases disability 329324 Inverse Klippel-Trénaunay syndrome 15 Cases 261236 16p13.11 microdeletion syndrome 15 Cases 280133 Complement component 3 deficiency 15 Cases Severe intellectual disability and progressive spastic paraplegia Peripheral neuropathy-myopathy-hoarseness397744 hearing loss syndrome 397615 Obesity due to CEP19 deficiency 401768 Proximal myopathy with extrapyramidal signs 280763

15 Cases 15 Cases 15 Cases

15 Cases Intrauterine growth restriction-short stature-early 436144 15 Cases adult-onset diabetes syndrome 436169 Thrombomodulin-related bleeding disorder 15 Cases 98949 Complete cryptophthalmia 15 Cases 978 ADULT syndrome 14 Cases 1193 Atkin-Flaitz syndrome 1658 Absence of fingerprints - congenital milia

14 Cases

1660 Dermo-odonto dysplasia 1516 Craniofacial dyssynostosis

14 Cases

2789 Lateral meningocele syndrome 1441 Ring chromosome 17

14 Cases

Autosomal recessive limb-girdle muscular dystrophy type 2G 36355 P2Y12 defect 79322 DPM1-CDG 34514

75378 Oligocone trichromacy

14 Cases 14 Cases 14 Cases 14 Cases 14 Cases 14 Cases 14 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

28

ORPHA Number

Disease or Group of diseases

Number of cases

90390 Anonychia - onychodystrophy 14 Cases 93356 Spondyloepimetaphyseal dysplasia, Missouri type 14 Cases 228415 5q35 microduplication syndrome 14 Cases 238750 4q21 microdeletion syndrome 14 Cases Autosomal recessive limb-girdle muscular 206549 14 Cases dystrophy type 2L 199351 Adult-onset dystonia-parkinsonism 14 Cases 306507 LAMB2-related infantile-onset nephrotic syndrome 14 Cases Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome Autosomal recessive mendelian susceptibility to 319569 mycobacterial diseases due to partial IFNgammaR1 deficiency 261257 Distal 17p13.3 microdeletion syndrome Retinal dystrophy with inner retinal dysfunction 397758 and ganglion cell anomalies 401849 Autosomal spastic paraplegia type 72 Microcornea-myopic chorioretinal atrophy369970 telecanthus syndrome Autosomal recessive severe congenital 423384 neutropenia due to JAGN1 deficiency 431272 X-linked scapuloperoneal muscular dystrophy 1394 Cerebro-facio-thoracic dysplasia 314394

2021 Fibrochondrogenesis 50945 Blomstrand lethal chondrodysplasia 101102 Charcot-Marie-Tooth disease type 2H Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins Non-acquired combined pituitary hormone 231720 deficiency with spine abnormalities 158025 Hereditary progressive mucinous histiocytosis Osteosclerosis-developmental delay178377 craniosynostosis syndrome 171612 Autosomal dominant spastic paraplegia type 37 Hypertelorism-preauricular sinus-punctual pits293958 deafness syndrome Congenital hereditary facial paralysis with variable 306530 hearing loss 313936 PENS syndrome X-linked mendelian susceptibility to mycobacterial 319605 diseases Severe early-onset obesity-insulin resistance 329249 syndrome due to SH2B1 deficiency Familial steroid-resistant nephrotic syndrome with 280406 sensorineural deafness 284160 8q21.11 microdeletion syndrome Tall stature-intellectual disability-facial 404443 dysmorphism syndrome 401953 Episodic ataxia with slurred speech 356978 D,L-2-hydroxyglutaric aciduria 217371

357008 Atypical hemolytic-uremic syndrome with DGKE

14 Cases 14 Cases 14 Cases 14 Cases 14 Cases

ORPHA Number

Disease or Group of diseases

deficiency 352665 9q21 microdeletion syndrome Pseudoxanthoma elasticum-like skin 436274 manifestations with retinis pigmentosa 435438 Progressive myoclonic epilepsy type 7 443098 Hyperostosis cranialis interna Intellectual disability-expressive aphasia-facial 436151 dysmorphism syndrome 844 Atrial tachyarrhythmia with short PR interval 956 Acro-pectoro-renal dysplasia

Number of cases

13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 12 Cases 12 Cases

Uveal coloboma-cleft lip and palate-intellectual 12 Cases disability Alopecia-epilepsy-pyorrhea-intellectual disability 1008 12 Cases syndrome 1190 Atelosteogenesis type I 12 Cases 1458 CODAS syndrome 12 Cases 1473

12 Cases

14 Cases

1471 Coloboma of macula - brachydactyly type B 2237 Hypoparathyroidism - deafness - renal disease

12 Cases

14 Cases

2224 Hypertryptophanemia 3460 Torg-Winchester syndrome 600 Distal myopathy with vocal cord weakness 59303 Ichthyosis - hypotrichosis - sclerosing cholangitis Distal myopathy with posterior leg and anterior 63273 hand involvement X-linked intellectual disability - macrocephaly 85320 macroorchidism Hemolytic anemia due to adenylate kinase 86817 deficiency 98772 Spinocerebellar ataxia type 19/22 93395 Ballard syndrome

12 Cases

14 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases

Hereditary sensory and autonomic neuropathy with spastic paraplegia 217346 19q13.11 microdeletion syndrome 217377 Microduplication Xp11.22-p11.23 syndrome 139578

13 Cases 13 Cases 13 Cases 13 Cases 13 Cases 13 Cases

12 Cases 12 Cases 12 Cases 12 Cases 12 Cases 12 Cases 12 Cases 12 Cases 12 Cases

12 Cases 210571 Dystonia 16 12 Cases 228387 Spondylo-megaepiphyseal-metaphyseal dysplasia 12 Cases 247794 Juvenile cataract - microcornea - renal glucosuria 12 Cases 171829 6q16 deletion syndrome 199340 Muscular dystrophy, Selcen type Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation 300547 Autosomal recessive infantile hypercalcemia Leukoencephalopathy-thalamus and brainstem 314051 anomalies-high lactate 314585 15q overgrowth syndrome 314588 Distal tetrasomy 15q 300570

13 Cases

12 Cases

12 Cases 12 Cases 12 Cases 12 Cases 12 Cases 12 Cases

12 Cases Mendelian susceptibility to mycobacterial diseases 319547 12 Cases due to complete IFNgammaR2 deficiency 261250 16q24.3 microdeletion syndrome 12 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

29

ORPHA Number

Disease or Group of diseases

Number of cases

ORPHA Number

261323 21q22.11q22.12 microdeletion syndrome 261272 17q12 microduplication syndrome

12 Cases

352712

268261 21q22.13q22.2 microdeletion syndrome Recessive intellectual disability - motor 280384 dysfunction - multiple joint contractures 280620 Progressive myoclonic epilepsy type 6 284460 Acute annular outer retinopathy

12 Cases

PRKAR1B-related neurodegenerative dementia with intermediate filaments Hypohidrosis-enamel hypoplasia-palmoplantar 363523 keratoderma-intellectual disability syndrome MYH7-related late-onset scapuloperoneal 437572 muscular dystrophy 2253 Foveal hypoplasia - presenile cataract 1231 Barber-Say syndrome 412066

Amelogenesis imperfecta-nephrocalcinosis 1031 syndrome 1757 Fibular dimelia - diplopodia 1497 X-linked complicated corpus callosum dysgenesis 1487 Cooks syndrome 2016 Cleft palate-lateral synechia syndrome Atrial septal defect - atrioventricular conduction 1479 defects 3063 X-linked intellectual disability, Snyder type 2987 Antecubital pterygium syndrome 2832 Short tarsus - absence of lower eyelashes 2854 Fuhrmann syndrome Trichomegaly - retina pigmentary degeneration dwarfism 79324 ALG12-CDG 79076 Juvenile polyposis of infancy 3363

88619 Familial acute necrotizing encephalopathy Combined immunodeficiency due to DOCK8 217390 deficiency 238744 Mammary-digital-nail syndrome Autosomal dominant limb-girdle muscular 238755 dystrophy type 1H 238722 Familial congenital mirror movements Hyperandrogenism due to cortisone reductase 168588 deficiency Familial scaphocephaly syndrome, McGillivray 168624 type 166272 Goldblatt syndrome 166282 Familial sick sinus syndrome Leukonychia totalis - acanthosis-nigricans-like lesions - abnormal hair 313850 Infantile cerebellar-retinal degeneration 261183 15q11.2 microdeletion syndrome 210133

280553 Fatal infantile hypertonic myofibrillar myopathy 397937 Polyglucosan body myopathy

12 Cases

12 Cases 12 Cases 12 Cases 12 Cases 12 Cases 12 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases 11 Cases

Disease or Group of diseases

Facial dysmorphism - immunodeficiency - livedo short stature Combined oxidative phosphorylation deficiency 444013 type 23 443988 Ventriculomegaly-cystic kidney disease 444051 20q11.2 microdeletion syndrome

Number of cases

11 Cases 11 Cases 11 Cases 11 Cases

1627 Deletion 5q35 968 Acromesomelic dysplasia, Hunter-Thomson type

10 Cases

916

10 Cases

Aase-Smith syndrome

10 Cases

1313 Infantile choroidocerebral calcification syndrome 10 Cases 1336 Hyperkeratosis-hyperpigmentation syndrome 10 Cases 1263 Boomerang dysplasia 10 Cases 1001 2q37 microdeletion syndrome 10 Cases Autosomal dominant palmoplantar keratoderma 1010 10 Cases and congenital alopecia 1150 Arthrogryposis multiplex congenita - whistling face 10 Cases 1952 Pacman dysplasia 10 Cases 1824 Lowry-Wood syndrome X-linked intellectual disability - Dandy-Walker 1568 malformation - basal ganglia disease - Seizures 1788 Acrofacial dysostosis, Rodríguez type 1490 Corneal dystrophy - perceptive deafness

10 Cases

1426 Greenberg dysplasia Pancreatic hypoplasia - diabetes - congenital heart 2255 disease 2319 Juberg-Hayward syndrome 2081 Cerebral gigantism - jaw cysts

10 Cases

Gaucher disease - ophthalmoplegia 2072 cardiovascular calcification 2047 Flynn-Aird syndrome 2658 Lenz-Majewski hyperostotic dwarfism

10 Cases 10 Cases 10 Cases

10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases

Muscular atrophy - ataxia - retinitis pigmentosa 10 Cases diabetes mellitus Hereditary myoclonus - progressive distal muscular 2590 10 Cases atrophy 2439 Patterson-Stevenson-Fontaine syndrome 10 Cases 2371 Lethal Larsen-like syndrome 10 Cases 2579

10 Cases

11 Cases

2329 Karsch-Neugebauer syndrome 3032 NPHP3-related Meckel-like syndrome

10 Cases

11 Cases

2959 Progeria - short stature - pigmented nevi 2872 Cardiocranial syndrome, Pfeiffer type

10 Cases

11 Cases

2839 Pelvis-shoulder dysplasia 2880 Phosphoenolpyruvate carboxykinase deficiency

11 Cases

1171

11 Cases

11 Cases 11 Cases 11 Cases 11 Cases

Cerebellar ataxia - areflexia - pes cavus - optic atrophy - sensorineural hearing loss 3317 Thoracolaryngopelvic dysplasia 3469 XK aprosencephaly 39

Acromelanosis 69739 Athabaskan brainstem dysgenesis syndrome

10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

30

ORPHA Number

Disease or Group of diseases

66637 Diaphanospondylodysostosis 66625 Cerebro-oculo-nasal syndrome

Number of cases

10 Cases 10 Cases

Hyperinsulinism due to short chain 3-hydroxylacyl10 Cases CoA dehydrogenase deficiency 46627 Char syndrome 10 Cases 79279 Alpha-N-acetylgalactosaminidase deficiency type 1 10 Cases 71212

79280 Alpha-N-acetylgalactosaminidase deficiency type 2 10 Cases 79281 Alpha-N-acetylgalactosaminidase deficiency type 3 10 Cases 79321 ALG3-CDG 79083 PPARG-related familial partial lipodystrophy 90398 91135 89841 85336 85329 86918 85174

10 Cases

10 Cases Localized lichen myxedematosus with mixed 10 Cases features of different subtypes Body skin hyperlaxity due to vitamin K-dependent 10 Cases coagulation factor deficiency Centripetalis recessive dystrophic epidermolysis 10 Cases bullosa X-linked neurodegenerative syndrome, Hamel type 10 Cases X-linked intellectual disability - hypotonia - facial 10 Cases dysmorphism - aggressive behavior Diffuse palmoplantar keratoderma-acrocyanosis 10 Cases syndrome Pseudodiastrophic dysplasia 10 Cases

85191 Singleton-Merten dysplasia 85163 Hypomyelination - congenital cataract

10 Cases

85274 Syndromic X-linked intellectual disability 7 97340 Hunter-McAlpine craniosynostosis

10 Cases

97240 Zebra body myopathy 93599 Primary hyperoxaluria type 2

10 Cases

93406 Syndactyly type 5 139406 Encephalopathy due to prosaposin deficiency

10 Cases

139426 Perioral myoclonia with absences 101111 Spinocerebellar ataxia type 25

10 Cases

99954 Charcot-Marie-Tooth disease type 4H 100013 Lissencephaly with cerebellar hypoplasia type C

10 Cases

99843 Leukocyte adhesion deficiency type II 220465 Laron syndrome with immunodeficiency

10 Cases

Ehlers-Danlos syndrome due to tenascin-X 230839 deficiency Syndromic multisystem autoimmune disease due 228426 to Itch deficiency Progressive supranuclear palsy - progressive non 240112 fluent aphasia Dominant hypophosphatemia with nephrolithiasis 244305 or osteoporosis Familial clubfoot due to 17q23.1q23.2 238578 microduplication 254504 Inhalational botulism 254411 Annular atrophic lichen planus 163966

X-linked dominant chondrodysplasia, ChassaingLacombe type

10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases 10 Cases

ORPHA Number

Disease or Group of diseases

Number of cases

140969 Saldino-Mainzer syndrome 141007 Orofaciodigital syndrome type 9

10 Cases

168796 Heart-hand syndrome, Slovenian type Combined immunodeficiency due to CRAC channel 169090 dysfunction 166073 Pontocerebellar hypoplasia type 6 168486 Congenital neuronal ceroid lipofuscinosis

10 Cases

178330 Heinz body anemia 171881 Cap myopathy

10 Cases

10 Cases

10 Cases 10 Cases 10 Cases 10 Cases

Sterile multifocal osteomyelitis with periostitis and 10 Cases pustulosis Benign familial nocturnal alternating hemiplegia of 209973 10 Cases childhood 294016 Microcephaly-capillary malformation syndrome 10 Cases Transient infantile hypertriglyceridemia and 300293 10 Cases hepatosteatosis 313906 Congenital pancreatic cyst 10 Cases Segmental progressive overgrowth syndrome with 314662 10 Cases fibroadipose hyperplasia Autosomal recessive congenital cerebellar ataxia 324262 10 Cases due to MGLUR1 deficiency 325004 CANDLE syndrome 10 Cases 261211 16p11.2p12.2 microdeletion syndrome 10 Cases 210115

263458 Hyperinsulinism due to INSR deficiency 263482 Spondyloepiphyseal dysplasia, Maroteaux type Xeroderma pigmentosum complementation group 276261 E Xeroderma pigmentosum complementation group 276267 G 276280 Hemihyperplasia-multiple lipomatosis syndrome 280615 Hemoglobinopathy Toms River

10 Cases 10 Cases 10 Cases 10 Cases 10 Cases

10 Cases Pseudoxanthomatous diffuse cutaneous 280794 10 Cases mastocytosis Multiple congenital anomalies - hypotonia 280633 10 Cases seizures syndrome 284227 TEMPI syndrome 10 Cases ADNP-related multiple congenital anomalies404448 10 Cases intellectual disability-autism spectrum disorder Huntington disease-like syndrome due to C9ORF72 401901 10 Cases expansions Hypomyelination with brain stem and spinal cord 363412 10 Cases involvement and leg spasticity 352629 16q24.1 microdeletion syndrome 10 Cases Autosomal recessive cerebellar ataxia with late352641 10 Cases onset spasticity 352734 Minimal pigment oculocutaneous albinism type 1 10 Cases Temperature-sensitive oculocutaneous albinism 352737 10 Cases type 1 353320 Pyruvate carboxylase deficiency, benign type 10 Cases Intellectual disability-severe speech delay-mild 391372 10 Cases dysmorphism syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

31

ORPHA Number

Disease or Group of diseases

Autoimmune encephalopathy with parasomnia and obstructive sleep apnea 309246 GM2 gangliosidosis, AB variant Fatal congenital hypertrophic cardiomyopathy due 439854 to glycogen storage disease 1345 Cardiomyopathy - cataract - hip spine disease 1264 Tricho-retino-dento-digital syndrome 420789

Brachymorphism - onychodysplasia dysphalangism 1553 Curry-Jones syndrome 2213 Hypertelorism-microtia-facial clefting syndrome 1292

Number of cases

10 Cases 10 Cases 10 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases

2008 Acro-cardio-facial syndrome 2707 Oculocerebrofacial syndrome, Kaufman type

9 Cases

2557 Mietens syndrome 33574 Gamma-glutamylcysteine synthetase deficiency

9 Cases

3-hydroxy-3-methylglutaryl-CoA synthase 35701 deficiency 35704 L-Arginine:glycine amidinotransferase deficiency 35107 Desmosterolosis 69737 Bosley-Salih-Alorainy syndrome 79405 Junctional epidermolysis bullosa inversa

9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases

79333 COG7-CDG 9 Cases 93317 Spondylometaphyseal dysplasia, Sedaghatian type 9 Cases 85338 X-linked intellectual disability - ataxia - apraxia 9 Cases Macrostomia - preauricular tags - external 9 Cases ophthalmoplegia 85277 X-linked intellectual disability, Cantagrel type 9 Cases 85199 Craniosynostosis - anal anomalies - porokeratosis 9 Cases 85286 X-linked intellectual disability, Shashi type 9 Cases 83619

137871 Laminopathy type Decaudain-Vigouroux 137628 Cardiac anomalies - heterotaxy Combined immunodeficiency T+ B+ due to partial 231154 RAG1 deficiency X-linked intellectual disability - spastic 163982 quadriparesis 46,XY disorder of sex development - adrenal 168558 insufficiency due to CYP11A1 deficiency 209951 Autosomal recessive spastic paraplegia type 18 293939 Distal Xq28 microduplication syndrome 293948 1p21.3 microdeletion syndrome 314466 Atypical Meigs syndrome Developmental and speech delay due to SOX5 deficiency 314679 Cerebro-facio-articular syndrome Autosomal dominant intermediate Charcot-Marie324585 Tooth disease with neuropathic pain 329478 Adult-onset distal myopathy due to VCP mutation 261279 17q23.1q23.2 microdeletion syndrome 313892

261349 2p15p16.1 microdeletion syndrome

9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases

ORPHA Number

Disease or Group of diseases

Number of cases

263487 COG5-CDG Moyamoya angiopathy-short stature-facial 280679 dysmorphism-hypergonadotropic hypogonadism Periodic paralysis with later-onset distal motor 397750 neuropathy 1120 Lung agenesis - heart defect - thumb anomalies 401945 Moyamoya disease with early-onset achalasia

9 Cases

363710 Spinocerebellar ataxia type 37 352745 Oculocutaneous albinism type 7

9 Cases

Congenital microcephaly-severe encephalopathyprogressive cerebral atrophy syndrome Ketoacidosis due to monocarboxylate transporter438075 1 deficiency STING-associated vasculopathy with onset in 425120 infancy 1226 Bamforth-Lazarus syndrome 1318 Campomelia, Cumming type 391376

9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 9 Cases 8 Cases 8 Cases

1327 Camptodactyly syndrome, Guadalajara type 1 1278 Brachydactyly - preaxial hallux varus

8 Cases

1188 Ataxia-deafness-intellectual disability syndrome Autosomal recessive palmoplantar keratoderma 1366 and congenital alopecia 1454 Joubert syndrome with hepatic defect Hydrocephalus - costovertebral dysplasia 2180 Sprengel anomaly 2206 Ankylosing vertebral hyperostosis with tylosis 2107 Hall-Riggs syndrome

8 Cases

2563 MOMO syndrome 2561 Ackerman syndrome

8 Cases

X-linked intellectual disability - dysmorphism cerebral atrophy 3219 Fountain syndrome 2326 Kallmann syndrome - heart disease 2958

3474 CHIME syndrome 33572 5-oxoprolinase deficiency Autosomal dominant familial hematuria - retinal 73229 arteriolar tortuosity - contractures 79325 ALG8-CDG 85282 MEHMO syndrome 85273 X-linked intellectual disability, Abidi type 85289 X-linked intellectual disability, Vitale type Leukoencephalopathy-ataxia-hypodontiahypomyelination syndrome 210144 Lethal polymalformative syndrome, Boissel type 221054 Acrocephalopolydactyly 137639

Microcornea - posterior megalolenticonus 231736 persistent fetal vasculature - coloboma 251295 Pigmented paravenous retinochoroidal atrophy 251290 Parietal foramina with cleidocranial dysplasia

8 Cases

8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

32

ORPHA Number

Disease or Group of diseases

140936 Lelis syndrome 178506 Brain calcification, Rajab type

Number of cases

8 Cases 8 Cases

178389 Osteopetrosis - hypogammaglobulinemia 8 Cases Amelogenesis imperfecta-gingival hyperplasia 171836 8 Cases syndrome 183678 Hermansky-Pudlak syndrome with neutropenia 8 Cases Sodium channelopathy-related small fiber 306577 8 Cases neuropathy Porencephaly-microcephaly-bilateral congenital 306547 8 Cases cataract syndrome 314811 Short stature due to GHSR deficiency 8 Cases Mitochondrial hypertrophic cardiomyopathy with 314637 8 Cases lactic acidosis due to MTO1 deficiency 324321 Sinoatrial node dysfunction and deafness 8 Cases Mendelian susceptibility to mycobacterial diseases 319595 8 Cases due to partial STAT1 deficiency Autosomal dominant Charcot-Marie-Tooth disease 329258 8 Cases type 2Q Autosomal recessive limb-girdle muscular 352479 8 Cases dystrophy type 2U 261483 Xq27.3q28 duplication syndrome 8 Cases 263665 NK-cell enteropathy 8 Cases Premature aging appearance-developmental delay-cardiac arrhythmia syndrome 280325 Distal monosomy 12p Autosomal recessive limb-girdle muscular 280333 dystrophy type 2P Joubert syndrome with Jeune asphyxiating 397715 thoracic dystrophy Alacrimia-choreoathetosis-liver dysfunction 404454 syndrome 401942 Familial median cleft of the upper and lower lips 397590 Silver-Russell syndrome due to a point mutation 276432

Brain dopamine-serotonin vesicular transport 352649 disease Digital anomalies - intellectual disability - short 352487 stature Autosomal dominant intermediate Charcot-Marie352670 Tooth disease type F 352675 X-linked Charcot-Marie-Tooth disease type 6 Autism spectrum disorder-epilepsy-arthrogryposis 370943 syndrome Severe combined immunodeficiency due to CTPS1 420573 deficiency Lethal neonatal spasticity-epileptic 435845 encephalopathy syndrome 420686 Woolly hair-palmoplantar keratoderma syndrome 399096 Distal anoctaminopathy 435638 3p25.3 microdeletion syndrome 438274 GCGR-related hyperglucagonemia Ocular albinism with late-onset sensorineural 1000 deafness

ORPHA Number

Disease or Group of diseases

Number of cases

958 Acro-renal-mandibular syndrome 7 Cases 2598 Mitochondrial myopathy and sideroblastic anemia 7 Cases 1131 X-linked mandibulofacial dysostosis 7 Cases 1842 Bone dysplasia, lethal Holmgren type 7 Cases 1574 Retinal degeneration - nanophthalmos - glaucoma Primary hypergonadotropic hypogonadism 2232 partial alopecia 2095 Gorlin-Chaudhry-Moss syndrome Möbius syndrome - axonal neuropathy 2560 hypogonadotropic hypogonadism 3194 Stern-Lubinsky-Durrie syndrome 3087 Retinohepatoendocrinologic syndrome 3078 2920 3341 1901

Severe X-linked intellectual disability, Gustavson type Oliver syndrome Torticollis - keloids - cryptorchidism - renal dysplasia Ehlers-Danlos syndrome, dermatosparaxis type

33573 Gamma-glutamyl transpeptidase deficiency 38874 Dihydropyrimidinuria 338

7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases

Familial multiple fibrofolliculoma Woolly hair-palmoplantar keratoderma-dilated 65282 cardiomyopathy syndrome 66631 CEDNIK syndrome 71526 Obesity due to pro-opiomelanocortin deficiency

7 Cases

79323 MPDU1-CDG 79094 Grange syndrome

7 Cases

93316 Spondylometaphyseal dysplasia, Schmidt type X-linked neurodegenerative syndrome, Bertini 85334 type Congenital malabsorptive diarrhea due to paucity 83620 of enteroendocrine cells 93382 Brachydactyly type A6 139474 17q11.2 microduplication syndrome

7 Cases

101078 X-linked Charcot-Marie-Tooth disease type 4 211067 Episodic ataxia type 5

7 Cases 7 Cases

8 Cases

228379 Virus-associated trichodysplasia spinulosa Patent ductus arteriosus - bicuspid aortic valve 228190 hand anomalies 228169 Autosomal dominant striatal neurodegeneration 247198 Progressive cerebello-cerebral atrophy

7 Cases

8 Cases

254531 Paternal 14q32.2 hypomethylation syndrome 251383 CK syndrome

7 Cases

8 Cases

163693 2p21 microdeletion syndrome 163976 X-linked intellectual disability, Van Esch type

8 Cases

163979

8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases 8 Cases

8 Cases

8 Cases 7 Cases

7 Cases 7 Cases 7 Cases 7 Cases

7 Cases 7 Cases 7 Cases 7 Cases 7 Cases

7 Cases 7 Cases 7 Cases 7 Cases 7 Cases

X-linked intellectual disability - craniofacioskeletal 7 Cases syndrome 178338 UV-sensitive syndrome 7 Cases 209970 Episodic ataxia type 7 7 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

33

ORPHA Number

Disease or Group of diseases

Deficiency in anterior pituitary function-variable immunodeficiency syndrome Progeroid and marfanoid aspect-lipodystrophy 300382 syndrome Combined immunodeficiency due to STK4 314689 deficiency Severe neonatal hypotonia-seizures314655 encephalopathy syndrome due to 5q31.3 microdeletion X-linked immunodeficiency with magnesium 317476 defect, Epstein-Barr virus infection and neoplasia 329329 Autosomal recessive frontotemporal pachygyria Microcephalic primordial dwarfism due to ZNF335 329228 deficiency 324632 Hendra virus infection 329802 5p13 microduplication syndrome 293978

261229 14q11.2 microduplication syndrome 263347 MRCS syndrome Autosomal semi-dominant severe lipodystrophic 280365 laminopathy Skin fragility-woolly hair-palmoplantar 293165 keratoderma syndrome 397695 3q27.3 microdeletion syndrome Intellectual disability-coarse face-macrocephaly397709 cerebellar hypotrophy syndrome Intellectual disability-facial dysmorphism 404440 syndrome due to SETD5 haploinsufficiency Multisystemic smooth muscle dysfunction 404463 syndrome 401785 Autosomal recessive spastic paraplegia type 62 397941 MAN1B1-CDG Intellectual disability-seizures-macrocephaly369950 obesity syndrome Severe motor and intellectual disabilities369939 sensorineural deafness-dystonia syndrome Ataxia-intellectual disability-oculomotor apraxia370022 cerebellar cysts syndrome Congenital neutropenia-myelofibrosis369852 nephromegaly syndrome 363396 High myopia-sensorineural deafness syndrome 357001 19p13.13 microdeletion syndrome Autosomal recessive congenital cerebellar ataxia 363432 due to GRID2 deficiency 352490 Autism spectrum disorder due to AUTS2 deficiency Focal epilepsy-intellectual disability-cerebro352587 cerebellar malformation 352582 Familial infantile myoclonic epilepsy 353298 Roifman syndrome 420561 Temple-Baraitser syndrome 439822 PDE4D haploinsufficiency syndrome 436242

Number of cases

7 Cases 7 Cases 7 Cases 7 Cases

ORPHA Number

Autosomal dominant Charcot-Marie-Tooth disease type 2 due to VCP mutation Primary immunodeficiency due to STAT2 431166 deficiency 3204 Stormorken-Sjaastad-Langslet syndrome 1951 Epilepsy telangiectasia 435387

991 1078

7 Cases

1115

7 Cases

1808

7 Cases

1786

7 Cases

1555

7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases

Disease or Group of diseases

2306

PAGOD syndrome Thumb stiffness - brachydactyly - intellectual disability Recessive aplasia cutis congenita of limbs Hidrotic ectodermal dysplasia, Christianson-Fourie type Acrofacial dysostosis, Catania type Cutis gyrata - acanthosis nigricans craniosynostosis Isotretinoin-like syndrome

7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases 7 Cases

Familial atrial tachyarrhythmia-infra-Hisian cardiac 7 Cases conduction disease

7 Cases 7 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases

6 Cases 1051 Ramos-Arroyo syndrome 6 Cases Hypogonadotropic hypogonadism - frontoparietal 2230 6 Cases alopecia Blepharophimosis - ptosis - esotropia - syndactyly 2057 6 Cases short stature 2117 Hartsfield-Bixler-Demyer syndrome 6 Cases 2824 Paraplegia - intellectual disability - hyperkeratosis 6 Cases 2339 Keratosis follicularis - dwarfism - cerebral atrophy 6 Cases 3175 Spasticity - intellectual disability - X-linked epilepsy 6 Cases X-linked intellectual disability - psychosis macroorchidism 2934 Polysyndactyly - cardiac malformation 2804 W syndrome 3077

7 Cases

Number of cases

6 Cases 6 Cases 6 Cases

3220 Deafness - enamel hypoplasia - nail defects Symphalangism with multiple anomalies of hands 3246 and feet 66518 Short fifth metacarpals - insulin resistance Megalencephaly - polymicrogyria - postaxial 83473 polydactyly - hydrocephalus 79106 Eiken syndrome 85337 X-linked intellectual disability, Zorick type

6 Cases

85276 X-linked intellectual disability, Armfield type 93973 Carpenter-Waziri syndrome

6 Cases

101008 Autosomal recessive spastic paraplegia type 28 211017 Spinocerebellar ataxia type 30

6 Cases

230851 Ehlers-Danlos syndrome, cardiac valvular type Severe combined immunodeficiency due to 228003 CORO1A deficiency 244310 RFT1-CDG 254525 Paternal 14q32.2 microdeletion syndrome

6 Cases

6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases

6 Cases 6 Cases 6 Cases

254528 Maternal 14q32.2 microdeletion syndrome 6 Cases Autosomal recessive spastic ataxia - optic atrophy 254343 6 Cases - dysarthria 254346 19p13.12 microdeletion syndrome 6 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

34

ORPHA Number

Disease or Group of diseases

Autosomal recessive limb-girdle muscular dystrophy type 2Q 247820 Ectodermal dysplasia - syndactyly syndrome Syndactyly - telecanthus - anogenital and renal 140952 malformations 157820 Cold-induced sweating syndrome Ehlers-Danlos syndrome, spondylocheirodysplastic 157965 type 46,XY gonadal dysgenesis - motor and sensory 168563 neuropathy 168984 CLAPO syndrome 169464 Primary CD59 deficiency 254361

178303 8q22.1 microdeletion syndrome 199332 Endocrine-cerebro-osteodysplasia syndrome Ehlers-Danlos syndrome, kyphoscoliotic and 300179 deafness type 314399 Autosomal dominant aplasia and myelodysplasia 313884 12p12.1 microdeletion syndrome Combined immunodeficiency due to ORAI1 317428 deficiency 324569 Pontocerebellar hypoplasia type 8 Progressive external ophthalmoplegia - myopathy 352447 - emaciation 231537 Hermansky-Pudlak syndrome type 8 Fatal multiple mitochondrial dysfunction 401874 syndrome type 2 401777 Optic atrophy-intellectual disability syndrome 398069 Prader-Willi syndrome due to point mutation Acute infantile liver failure-multisystemic 370088 involvement syndrome Leukoencephalopathy with mild cerebellar ataxia 363540 and white matter edema Severe neurodegenerative syndrome with 363400 lipodystrophy Nail and teeth abnormalities-marginal 423454 palmoplantar keratoderma-oral hyperpigmentation syndrome 398127 Neonatal scleroderma Autoimmune hemolytic anemia-autoimmune 444463 thrombocytopenia-primary immunodeficiency syndrome Severe intellectual disability-hypotonia436141 strabismus-coarse face-planovalgus syndrome Contractures-developmental delay-Pierre Robin 436003 syndrome 929 Achalasia - microcephaly Alopecia-contractures-dwarfism-intellectual 1005 disability syndrome Choanal atresia-hearing loss-cardiac defects1200 craniofacial dysmorphism syndrome 1094 Anonychia - microcephaly 1113 Aphalangy - syndactyly - microcephaly

Number of cases

6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases 6 Cases

ORPHA Number

Number of cases

1811 Odontomicronychial dysplasia 1657 Dermatoosteolysis, Kirghizian type

5 Cases

1784 Acro-fronto-facio-nasal dysostosis 1514 Craniodigital syndrome - intellectual disability

5 Cases

1562 Dacryocystitis - osteopoikilosis 1535 Craniosynostosis - dysmorphism - brachydactyly

5 Cases

2085 Glaucoma - sleep apnea 2077 German syndrome

5 Cases

2111 Cystic hamartoma of lung and kidney 2714 Oculo-palato-cerebral syndrome

5 Cases

Nephrosis - deafness - urinary tract - digital 2669 malformations Nephropathy-deafness-hyperparathyroidism 2668 syndrome 2571 X-linked immunoneurologic disorder 2565 Mononen-Karnes-Senac syndrome

5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases

2558 Mikati-Najjar-Sahli syndrome 2496 Mesomelia-synostoses syndrome

5 Cases

2351 Kousseff syndrome 3168 Sillence syndrome

5 Cases

5 Cases

5 Cases 3128 Sakati-Nyhan syndrome 5 Cases Intellectual disability - balding - patella luxation 3041 5 Cases acromicria 3003 Pyknoachondrogenesis 5 Cases 2823 Paraplegia - brachydactyly - cone-shaped epiphysis 5 Cases

6 Cases

3304

6 Cases

1415

6 Cases

1272

6 Cases

Disease or Group of diseases

1129 69736

Fallot complex - intellectual disability - growth delay Cholestasis-pigmentary retinopathy-cleft palate syndrome Fine-Lubinsky syndrome Arachnodactyly - abnormal ossification intellectual disability Acute bilateral depigmentation of the iris

5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases

6 Cases

65287 Beta-ureidopropionase deficiency Growth delay due to insulin-like growth factor 73272 type 1 deficiency 50815 Branchiogenic deafness syndrome 83472 CAMOS syndrome 75374 Bradyopsia 79095 Congenital bile acid synthesis defect type 4

5 Cases

6 Cases

90646 Deafness - hypogonadism Localized lichen myxedematosus with monoclonal 90399 gammopathy or systemic symptoms Acanthosis nigricans - Insulin resistance - muscle 90301 cramps - acral enlargement Lissencephaly type 3 - familial fetal akinesia 86821 sequence 86914 Lymphedema - cerebral arteriovenous anomaly 85112 Palmoplantar keratoderma - XX sex reversal -

5 Cases

6 Cases 6 Cases

6 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases

5 Cases 5 Cases 5 Cases 5 Cases

5 Cases 5 Cases 5 Cases 5 Cases 5 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

35

ORPHA Number

Disease or Group of diseases

predisposition to squamous cell carcinoma 85175 Astley-Kendall dysplasia X-linked intellectual disability - cubitus valgus 85280 dysmorphism 85295 HSD10 disease, atypical type 85297 X-linked spinocerebellar ataxia type 3

Number of cases

5 Cases 5 Cases 5 Cases 5 Cases

85284 BRESEK syndrome 97341 Persistent placoid maculopathy

5 Cases

94056 Humero-ulnar synostosis 93975 Renier-Gabreels-Jasper syndrome

5 Cases

139515 Charcot-Marie-Tooth disease type 4J 137834 Frank-Ter Haar syndrome

5 Cases

Microcephaly - facio-cardio-skeletal syndrome, 217026 Hadziselimovic type 210141 Inherited congenital spastic tetraplegia Frontonasal dysplasia with alopecia and genital 228390 anomaly 228227 Late-onset focal dermal elastosis 238766 Ptosis - syndactyly - learning difficulties

314652 Variant ABeta2M amyloidosis Combined oxidative phosphorylation defect type 324535 11 Autosomal recessive mendelian susceptibility to 319574 mycobacterial diseases due to partial IFNgammaR2 deficiency Beta-propeller protein-associated 329284 neurodegeneration Methylmalonic aciduria due to transcobalamin 280183 receptor defect

Familial omphalocele syndrome with facial dysmorphism Severe neonatal lactic acidosis due to NFS1-ISD11 397593 complex deficiency Infantile cerebral and cerebellar atrophy with 402364 postnatal progressive microcephaly 401986 1p31p32 microdeletion syndrome 98676 Autosomal recessive isolated optic atrophy 280403

Number of cases

5 Cases 5 Cases 5 Cases 5 Cases

5 Cases 5 Cases

369847

5 Cases

5 Cases 5 Cases 5 Cases 5 Cases

Recurrent infections - inflammatory syndrome due 5 Cases to zinc metabolism disorder 157954 ANE syndrome 5 Cases 169079 Cernunnos-XLF deficiency 5 Cases 168443 Spondyloepimetaphyseal dysplasia - hypotrichosis 5 Cases

Congenital cataract-hearing loss-severe 300313 developmental delay syndrome 314555 Craniofacial dysplasia-osteopenia syndrome 314667 TMEM165-CDG

Disease or Group of diseases

5 Cases 369920 Pontocerebellar hypoplasia type 9 5 Cases Combined oxidative phosphorylation defect type 369913 5 Cases 17 363654 X-linked parkinsonism-spasticity syndrome 5 Cases 363618 LMNA-related cardiocutaneous progeria syndrome 5 Cases

5 Cases

251523

Autosomal recessive lower motor neuron disease 206580 with childhood onset 199343 EAST syndrome Hypoinsulinemic hypoglycemia and body 293964 hemihypertrophy Childhood encephalopathy due to thiamine 293955 pyrophosphokinase deficiency 293462 Pre-Descemet corneal dystrophy Multiple congenital anomalies-hypotonia-seizures 300496 syndrome type 2 300504 Onychocytic matricoma 300552 Follicular cholangitis and pancreatitis

ORPHA Number

5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases

Intellectual disability-hyperkinetic movementtruncal ataxia syndrome Cryptosporidiosis - chronic cholangitis - liver 357329 disease 352596 Progressive myoclonic epilepsy with dystonia Autoimmune enteropathy and endocrinopathy391487 susceptibility to chronic infections syndrome 423275 Spinocerebellar ataxia type 40 444002 11q22.2q22.3 microdeletion syndrome Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome Craniosynostosis - Dandy-Walker malformation 1538 hydrocephalus 1135 Arrhinia - choanal atresia - microphthalmia 2431 Central bilateral macrogyria

445062

921

Abruzzo-Erickson syndrome

5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 5 Cases 4 Cases 4 Cases 4 Cases 4 Cases

1240 Metaphyseal acroscyphodysplasia 1307 Distal limb deficiencies - micrognathia syndrome

4 Cases

1261 Bonnemann-Meinecke-Reich syndrome 1104 Anophthalmia plus syndrome

4 Cases

1809 Hidrotic ectodermal dysplasia, Halal type 1790 Hypomandibular faciocranial dysostosis

4 Cases

1682 Arterial dissection - lentiginosis 1508 Coxoauricular syndrome

4 Cases

1435 Choroideremia - deafness - obesity Ichthyosis - alopecia - eclabion - ectropion 2269 intellectual disability 2150 Hirschsprung disease - type D brachydactyly Malignant hyperthermia - arthrogryposis 2215 torticollis 2050 Cole-Carpenter syndrome Diaphragmatic defect - limb deficiency - skull 2141 defect

4 Cases

4 Cases

4 Cases Aortic arch anomaly - peculiar facies - intellectual 1110 4 Cases disability 1117 Aplasia cutis - myopia 4 Cases 1816 Ectodermal dysplasia, Berlin type 4 Cases 4 Cases 4 Cases

4 Cases 4 Cases 4 Cases 4 Cases 4 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

36

ORPHA Number

Disease or Group of diseases

Number of cases

ORPHA Number

Disease or Group of diseases

1973 Faciocardiorenal syndrome Cleft lip/palate - intestinal malrotation 2001 cardiopathy 2723 Odontotrichomelic syndrome 2676 Neuroectodermal-endocrine syndrome

4 Cases

2589 Myoclonus-cerebellar ataxia-deafness syndrome Leukoencephalopathy-palmoplantar keratoderma 2386 syndrome 2328 Kapur-Toriello syndrome Intellectual disability - dysmorphism 3044 hypogonadism - diabetes mellitus 3052 X-linked intellectual disability - seizures - psoriasis Non-eruption of teeth - maxillary hypoplasia 2972 genu valgum 2946 Brachydactyly - long thumb 2865 Short stature - webbed neck - heart disease

4 Cases

4 Cases

94095

2919 Orofaciodigital syndrome type 5 2820 Spastic paraplegia - nephritis - deafness

4 Cases

94063

4 Cases

2168 Homocarnosinosis 3355 Trichoodontoonychial dysplasia

4 Cases

94065 15q24 microdeletion syndrome 93946 Hamel cerebro-palato-cardiac syndrome

4 Cases

1884 Ectopia lentis - chorioretinal dystrophy - myopia 1768 Familial caudal dysgenesis

4 Cases

93405 Syndactyly type 4 93352 Spondyloepimetaphyseal dysplasia, Shohat type

4 Cases

1423 Lethal recessive chondrodysplasia 806 Scott syndrome

4 Cases

69735 65743 65288 71269

Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome Autosomal dominant multiple pterygium syndrome Permanent neonatal diabetes mellitus - pancreatic and cerebellar agenesis Benign exophthalmos syndrome

4 Cases 4 Cases 4 Cases

4 Cases 4 Cases 4 Cases

85325 X-linked intellectual disability, Stevenson type 85323 X-linked intellectual disability, Seemanova type

Number of cases

Myopathy due to calsequestrin and SERCA1 protein overload Leukoencephalopathy - metaphyseal 83629 chondrodysplasia Microcephalic osteodysplastic dysplasia, Saul85172 Wilson type 85186 Endosteal sclerosis - cerebellar hypoplasia 85162 Facial onset sensory and motor neuronopathy 88635

85165

4 Cases 4 Cases 4 Cases

4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases

46059 Lathosterolosis 79329 MGAT2-CDG

4 Cases

79132 Sparse hair - short stature - skin anomalies Primary immunodeficiency with natural-killer cell 75391 deficiency and adrenal insufficiency 79022 Simpson-Golabi-Behmel syndrome type 2 77295 Odontoleukodystrophy

4 Cases

91131 DK1-CDG 91132 Ichthyosis-hypotrichosis syndrome

4 Cases

93333 Pelviscapular dysplasia Neurodegeneration due to 3-hydroxyisobutyryl88639 CoA hydrolase deficiency Primary immunodeficiency syndrome due to p14 90023 deficiency X-linked intellectual disability - corpus callosum 85330 agenesis - spastic quadriparesis X-linked intellectual disability - hypogonadism 85331 ichthyosis - obesity - short stature 85326 X-linked intellectual disability, Stoll type

4 Cases

4 Cases

4 Cases 4 Cases 4 Cases 4 Cases

4 Cases 4 Cases 4 Cases 4 Cases

85283 85285

Hereditary sensory and autonomic neuropathy 139573 with deafness and global delay 137911 Autism - facial port-wine stain Progressive demyelinating neuropathy with 217396 bilateral striatal necrosis Hereditary hypotrichosis with recurrent skin 217407 vesicles 210163 Congenital lethal myopathy, Compton-North type Pulmonary fibrosis - hepatic hyperplasia - bone 210136 marrow hypoplasia Severe early-onset axonal neuropathy due to NEFL 228374 deficiency 228399 8q12 microduplication syndrome 228240 Elastoderma Cutis laxa with severe pulmonary, gastrointestinal 221145 and urinary anomalies 247604 Juvenile primary lateral sclerosis Glaucoma secondary to spherophakia/ectopia 238763 lentis and megalocornea Infantile onset panniculitis with uveitis and 251304 systemic granulomatosis Microphthalmia - retinitis pigmentosa 251279 foveoschisis - optic disc drusen 251061 7q31 microdeletion syndrome 251056 6q25 microdeletion syndrome 250984 Autosomal recessive Stickler syndrome 250972 Polymicrogyria with optic nerve hypoplasia 247827

4 Cases

Severe achondroplasia - developmental delay acanthosis nigricans X-linked intellectual disability, Miles-Carpenter type X-linked intellectual disability, Schimke type Spondylocostal dysostosis - anal and genitourinary malformations 12q14 microdeletion syndrome

Ectodermal dysplasia - cutaneous syndactyly syndrome

4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

37

ORPHA Number

Disease or Group of diseases

Number of cases

247790 FTH1-related iron overload 158687 Lethal acantholytic epidermolysis bullosa

4 Cases

163649 Spondyloepiphyseal dysplasia, Nishimura type 163668 Spondyloepiphyseal dysplasia, MacDermot type

4 Cases

163654 Spondyloepiphyseal dysplasia, Cantu type 163971 X-linked intellectual disability, Cilliers type

4 Cases

140963 Bilateral microtia - deafness - cleft palate 140976 RHYNS syndrome

4 Cases

166024 Multiple epiphyseal dysplasia, Al-Gazali type Microcephaly - polymicrogyria - corpus callosum 171703 agenesis Craniosynostosis - hydrocephalus - Arnold-Chiari 171839 malformation type I - radioulnar synostosis 171844 Blindness-scoliosis-arachnodactyly syndrome 210128 Urocanic aciduria

4 Cases

209967 Episodic ataxia type 6 199337 Pancreatic insufficiency - anemia - hyperostosis

4 Cases

Lethal occipital encephalocele-skeletal dysplasia 293925 syndrome 293825 Congenital dyserythropoietic anemia type IV Hypogonadotropic hypogonadism-severe 293967 microcephaly-sensorineural hearing lossdysmorphism syndrome Painful orbital and systemic neurofibromas300501 marfanoid habitus syndrome 306550 FADD-related immunodeficiency 313781 20p13 microdeletion syndrome

4 Cases 4 Cases 4 Cases 4 Cases

4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases

313795 Jawad syndrome Hereditary sensory and autonomic neuropathy 314381 type 6 313855 FGFR2-related bent bone dysplasia 314721 Atypical dentin dysplasia due to SMOC2 deficiency

4 Cases

314632 Parkinsonism due to ATP13A2 deficiency 324313 9p13 microdeletion syndrome

4 Cases

X-linked mendelian susceptibility to mycobacterial 319612 diseases due to IKBKG deficiency Blepharophimosis-intellectual disability syndrome 329255 due to UBE3B deficiency 324581 Benign Samaritan congenital myopathy Mitochondrial DNA deletion syndrome with 352470 progressive myopathy Microcephaly-cerebellar hypoplasia-cardiac 329332 conduction defect syndrome 329341 Limbic encephalitis with DPP6 antibodies 261102 Distal 7q11.23 microduplication syndrome 261190 15q14 microdeletion syndrome Infantile spams - psychomotor retardation 263410 progressive brain atrophy - basal ganglia disease 264200 14q22q23 microdeletion syndrome 280142 Severe combined immunodeficiency due to LCK

4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases 4 Cases

ORPHA Number

Disease or Group of diseases

deficiency Hereditary sensorimotor neuropathy with 280598 hyperelastic skin Chondrodysplasia with joint dislocations, gPAPP 280586 type 280558 Warsaw breakage syndrome 280654 Autosomal recessive nail dysplasia

Number of cases

4 Cases 4 Cases 4 Cases

4 Cases 284339 Pontocerebellar hypoplasia type 7 4 Cases Periodic paralysis with transient compartment-like 397755 4 Cases syndrome Severe combined immunodeficiency due to IKK2 397787 4 Cases deficiency Short stature-auditory canal atresia-mandibular 397623 4 Cases hypoplasia-skeletal anomalies syndrome Diffuse cerebral and cerebellar atrophy-intractable 404437 4 Cases seizures-progressive microcephaly syndrome AHDC1-related intellectual disability-obstructive 412069 4 Cases sleep apnea-mild dysmorphism syndrome Autosomal recessive spondylometaphyseal 401979 4 Cases dysplasia, Mégarbané type Severe intellectual disability-progressive spastic 404473 4 Cases diplegia syndrome 404466 Female infertility due to zona pellucida defect 4 Cases Hyperammonemic encephalopathy due to 401948 4 Cases carbonic anhydrase VA deficiency 401780 Autosomal recessive spastic paraplegia type 61 4 Cases 401810 Autosomal recessive spastic paraplegia type 64 4 Cases 401835 Autosomal recessive spastic paraplegia type 70 1819 Epimetaphyseal skeletal dysplasia

4 Cases

4 Cases 398079 Prader-Willi-like syndrome due to point mutation 4 Cases Sacral agenesis-abnormal ossification of the 397927 vertebral bodies-persistent notochordal canal 4 Cases syndrome Microcephaly-thin corpus callosum-intellectual 397951 4 Cases disability syndrome 369942 CADDS 4 Cases Cardiac anomalies-developmental delay-facial 369891 4 Cases dysmorphism syndrome Severe intellectual disability-poor language363686 4 Cases strabismus-grimacing face-long fingers syndrome Mandibular hypoplasia-deafness-progeroid 363649 4 Cases syndrome Intellectual disability-seizures-hypotonia369837 4 Cases ophthalmologic-skeletal anomalies syndrome 363969 Autosomal recessive cerebral atrophy 4 Cases Ichthyosis-short stature-brachydactyly363992 4 Cases microspherophakia syndrome 363965 Koolen-De Vries syndrome due to a point mutation 4 Cases Short ulna - dysmorphism - hypotonia - intellectual 357175 4 Cases disability 356961 SLC35A2-CDG 4 Cases 356947 3q26q27 microdeletion syndrome 4 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

38

ORPHA Number

Disease or Group of diseases

Number of cases

ORPHA Number

Disease or Group of diseases

Number of cases

Developmental delay-microcephaly-facial 4 Cases dysmorphism syndrome, Hutterite type Severe feeding difficulties - failure to thrive 352577 4 Cases microcephaly due to ASXL3 deficiency Cobblestone lissencephaly without muscular or 352682 4 Cases ocular involvement 352709 CLN13 disease 4 Cases Progressive retinal dystrophy due to retinol 352718 4 Cases transport defect Autosomal recessive severe congenital 420702 4 Cases neutropenia due to CSF3R deficiency PCNA-related progressive neurodegenerative 438134 4 Cases photosensitivy syndrome 424027 Progressive myoclonic epilepsy type 8 4 Cases Lethal fetal brain malformation-duodenal atresia444069 4 Cases bilateral renal hypoplasia syndrome Peeling skin-leukonuchia-acral punctate keratoses444138 4 Cases cheilitis-knuckle pads syndrome 443995 Mandibulofacial dysostosis with alopecia 4 Cases 178400 Distal myopathy with anterior tibial onset 4 Cases

polydactyly 2153 Hirschsprung disease-nail hypoplasia-dysmorphism 3 Cases 2218 Cervical hypertrichosis - peripheral neuropathy 3 Cases

Periodic fever-infantile enterocolitis4 Cases autoinflammatory syndrome RARS-related autosomal recessive 438114 4 Cases hypomyelinating leukodystrophy 999 Ermine phenotype 3 Cases Congenital osteogenesis imperfecta - microcephaly 2772 3 Cases - cataracts Disorder of sex development - intellectual 2983 3 Cases disability 1259 Blepharoptosis - myopia - ectopia lentis 3 Cases Camptodactyly - fibrous tissue hyperplasia 1321 3 Cases skeletal dysplasia 1342 Heart-hand syndrome type 3 3 Cases 1299 Branchio-skeleto-genital syndrome 3 Cases

2516

363444

436166

1027 Autosomal recessive amelia Aniridia - ptosis - intellectual disability - familial 1067 obesity 1133 AREDYLD syndrome 1069 Aniridia-absent patella syndrome 1112 1116 1882 1495 1529

3 Cases 3 Cases 3 Cases 3 Cases

Aphalangy - hemivertebrae - urogenital-intestinal 3 Cases dysgenesis Aplasia cutis congenita - intestinal 3 Cases lymphangiectasia Hypohidrotic ectodermal dysplasia 3 Cases hypothyroidism - ciliary dyskinesia Intellectual disability - hypoplastic corpus callosum 3 Cases - preauricular tag Craniofacial-deafness-hand syndrome 3 Cases

1521 Craniofrontonasal dysplasia - Poland anomaly Hair defect - photosensitivity - intellectual 1408 disability 1389 Cortical blindness - intellectual disability -

2064 2091 2084 1972 1970 2736

Posterior fusion of lumbosacral vertebrae blepharoptosis Multinodular goiter - cystic kidney - polydactyly Glaucoma - ectopia - microspherophakia - stiff joints - short stature Lethal faciocardiomelic dysplasia Facial dysmorphism - macrocephaly - myopia Dandy-Walker malformation Lethal omphalocele-cleft palate syndrome

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

2751 Orofaciodigital syndrome type 2 2713 Oculoosteocutaneous syndrome

3 Cases

2613 Nail-patella-like renal disease 2608 N syndrome

3 Cases

2515 Microcephaly - cardiomyopathy 2521 Microcephaly - cleft palate

3 Cases

2437 2410 2409

Microcephaly - cardiac defect - lung malsegmentation Czeizel-Losonci syndrome Hypergonadotropic hypogonadism - cataract syndrome Lowry-MacLean syndrome

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

3172 Eyebrow duplication - syndactyly 3210 Summitt syndrome

3 Cases

3086 Autosomal dominant vitreoretinochoroidopathy 3088 Revesz syndrome

3 Cases

3010 Qazi-Markouizos syndrome Retinal ischemic syndrome - digestive tract small 3018 vessel hyalinosis - diffuse cerebral calcifications Absent thumb-short stature-immunodeficiency 2951 syndrome 2881 Cutaneous photosensitivity - lethal colitis Osteoporosis - oculocutaneous hypopigmentation 2786 syndrome 3326 Thymic-renal-anal-lung dysplasia 3328 Absent tibia - polydactyly - arachnoid cyst

3 Cases

3238 Cardiospondylocarpofacial syndrome 3404 Ulbright-Hodes syndrome

3 Cases

3369 2649 3433

3 Cases

1101

3 Cases

1383

3 Cases

1655

Trigonocephaly - short stature - developmental delay Short stature - intellectual disability - eye anomalies - cleft lip/palate Microcephaly - brachydactyly - kyphoscoliosis Anophthalmia - megalocornea - cardiopathy skeletal anomalies Cataract - deafness - hypogonadism Müllerian derivatives - lymphangiectasia polydactyly

3 Cases 3 Cases

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

39

ORPHA Number

1130 629 69125 66633 65798 73223 50811

Disease or Group of diseases

Arachnodactyly - intellectual disability dysmorphism Short stature due to growth hormone qualitative anomaly Anonychia with flexural pigmentation Sensorineural hearing loss - early graying essential tremor Goodman syndrome Global developmental delay - osteopenia ectodermal defect Lipodystrophy - intellectual disability - deafness

52054 Craniosynostosis - intracranial calcifications Agammaglobulinemia-microcephaly83617 craniosynostosis-severe dermatitis syndrome 79328 ALG9-CDG 79330 GCS1-CDG Seizures - intellectual disability due to hydroxylysinuria Osteosclerosis - ichthyosis - premature ovarian 75325 failure 77299 Microphthalmia - brain atrophy 93267 Cloverleaf skull - multiple congenital anomalies 79156

90030 85324 85321 86309 88618 86915

Number of cases

3 Cases 3 Cases

217382

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

Ptosis - upper ocular movement limitation 228396 absence of lacrimal punctum 254534 Maternal 14q32.2 hypermethylation syndrome 251066 8p11.2 deletion syndrome

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

163665 Spondyloepiphyseal dysplasia tarda, Kohn type 163961 X-linked intellectual disability, Kroes type

3 Cases

166068 Pontocerebellar hypoplasia type 5 166277 Suarez-Stickler syndrome

3 Cases

3 Cases 3 Cases

3 Cases 3 Cases

178396

3 Cases

3 Cases

93971 Chudley-Lowry-Hoar syndrome 3 Cases 93947 X-linked intellectual disability, Golabi-Ito-Hall type 3 Cases 139466 SERKAL syndrome 3 Cases Microcephaly - intellectual disability - phalangeal and neurological anomalies Hypotonia with lactic acidemia and 137908 hyperammonemia 103910 Congenital enterocyte heparan sulfate deficiency Intractable diarrhea - choanal atresia - eye 137622 anomalies 137625 Glycogen storage disease due to muscle and heart

Neurodegenerative syndrome due to cerebral folate transport deficiency 217017 Zechi-Ceide syndrome 230845 Ehlers-Danlos syndrome, vascular-like type

Number of cases

168448 Spondyloepimetaphyseal dysplasia, Bieganski type 3 Cases 168544 Spondylometaphyseal dysplasia, Golden type 3 Cases 168549 Axial spondylometaphyseal dysplasia 3 Cases

3 Cases

3 Cases X-linked intellectual disability 85317 hypogammaglobulinemia - progressive 3 Cases neurological deterioration X-linked intellectual disability - precocious puberty 85318 3 Cases - obesity 85290 X-linked intellectual disability, Wilson type 3 Cases 93970 Holmes-Gang syndrome 3 Cases

137658

Disease or Group of diseases

glycogen synthase deficiency 98908 Neutral lipid storage myopathy 217335 RIN2 syndrome

3 Cases

Hemolytic anemia due to glutathione reductase 3 Cases deficiency X-linked intellectual disability, Shrimpton type 3 Cases Deafness - intellectual disability, Martin-Probst 3 Cases type DPAGT1-CDG 3 Cases Psychomotor retardation due to S3 Cases adenosylhomocysteine hydrolase deficiency Lymphedema - atrial septal defects - facial changes 3 Cases

83642 Microcytic anemia with liver iron overload 85291 X-linked intellectual disability, Wittwer type

ORPHA Number

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

Hemorrhagic disease due to alpha-1-antitrypsin 3 Cases Pittsburgh mutation 171860 Intellectual disability - cataracts - kyphosis 3 Cases 171866 Spondyloepimetaphyseal dysplasia, aggrecan type 3 Cases Autosomal recessive limb-girdle muscular 206554 3 Cases dystrophy type 2M 300373 Familial infantile gigantism 3 Cases Severe congenital hypochromic anemia with 300298 3 Cases ringed sideroblasts Nephrotic syndrome-deafness-pretibial 300333 3 Cases epidermolysis bullosa syndrome Primary microcephaly-epilepsy-permanent 306558 3 Cases neonatal diabetes syndrome 313800 Optic nerve edema-splenomegaly syndrome 3 Cases Congenital nephrotic syndrome-interstitial lung 306504 3 Cases disease-epidermolysis bullosa syndrome Frontonasal dysplasia-severe microphthalmia306542 3 Cases severe facial clefting syndrome 314389 Xq12-q13.3 duplication syndrome 3 Cases Young adult-onset distal hereditary motor 314485 3 Cases neuropathy Autosomal recessive leukoencephalopathy with 314572 3 Cases ischemic stroke-retinitis pigmentosa syndrome Hypertrophic cardiomyopathy and renal tubular 324525 3 Cases disease due to mitochondrial DNA mutation 324290 Early-onset Lafora body disease 3 Cases Mendelian susceptibility to mycobacterial diseases 319563 3 Cases due to complete ISG15 deficiency Autoinflammatory syndrome with pyogenic 329173 3 Cases bacterial infection and amylopectinosis Congenital muscular dystrophy with intellectual 329178 3 Cases disability and severe epilepsy 324999 JMP syndrome 3 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

40

ORPHA Number

Disease or Group of diseases

Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay 261120 14q11.2 microdeletion syndrome 261144 14q12 microdeletion syndrome 330054

Number of cases

3 Cases 3 Cases 3 Cases

261295 20p12.3 microdeletion syndrome 263508 COG1-CDG

3 Cases

263516 Progressive myoclonic epilepsy type 3 280356 PLIN1-related familial partial lipodystrophy

3 Cases

280640 Occipital pachygyria and polymicrogyria 412035 13q12.3 microdeletion syndrome

3 Cases

3 Cases 3 Cases

3 Cases Early onset epileptic encephalopathy-cortical 411986 blindness-intellectual disability-facial dysmorphism 3 Cases syndrome Epidermolysis bullosa simplex due to exophilin 5 412189 3 Cases deficiency Autosomal recessive cerebellar ataxia-epilepsy404493 intellectual disability syndrome due to TUD 3 Cases deficiency 402082 Progressive myoclonic epilepsy type 5 3 Cases FBLN1-related developmental delay-central 404451 3 Cases nervous system anomaly-syndactyly syndrome 401859 Lipoic acid synthetase deficiency 3 Cases 401866 Spasticity-ataxia-gait anomalies syndrome 3 Cases 401935 14q24.1q24.3 microdeletion syndrome 401795 Autosomal recessive spastic paraplegia type 59 Severe intellectual disability-progressive postnatal 397933 microcephaly- midline stereotypic hand movements syndrome 397922 Ferro-cerebro-cutaneous syndrome Combined immunodeficiency due to MALT1 397964 deficiency Severe dermatitis-multiple allergies-metabolic 369992 wasting syndrome 370127 Medich giant platelet syndrome 370052 SCALP syndrome Intellectual disability-facial dysmorphism-hand anomalies syndrome Acroosteolysis-keloid-like lesions-premature aging 363665 syndrome Intellectual disability-feeding difficulties363611 developmental delay-microcephaly syndrome Autosomal recessive intermediate Charcot-Marie369867 Tooth disease type C Autosomal recessive limb-girdle muscular 369840 dystrophy type 2S 363981 Charcot-Marie-Tooth disease type 4B3 Intellectual disability - hypotonia - spasticity 356996 sleep disorder Mitochondrial DNA depletion syndrome, 363534 hepatocerebrorenal form Fetal akinesia-cerebral and retinal hemorrhage 363409 syndrome 370010

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

ORPHA Number

Disease or Group of diseases

Early-onset progressive neurodegeneration blindness - ataxia - spasticity 370938 Salt-and-pepper syndrome Severe intellectual disability-short stature391307 behavioral troubles-facial dysmorphism syndrome Infantile-onset mesial temporal lobe epilepsy with 391316 severe cognitive regression 391351 SURF1-related Charcot-Marie-Tooth disease type 4 Hereditary sensory and autonomic neuropathy 391397 type 7 Primary microcephaly-mild intellectual disability391408 young-onset diabetes syndrome 391457 HSD10 disease, neonatal type 391646 Feingold syndrome type 2 352654

420566 Bleeding disorder due to CalDAG-GEFI deficiency 420794 Cono-spondylar dysplasia Muscular dystrophy with progressive weakness, 424261 distal contractures and rigid spine Autosomal recessive intermediate Charcot-Marie435998 Tooth disease type D Retinitis pigmentosa-juvenile cataract-short 436245 stature-intellectual disability syndrome Microcephaly-complex motor and sensory axonal 423894 neuropathy 398117 Neonatal dermatomyositis 444048 46,XX ovarian dysgenesis-short stature syndrome Combined oxidative phosphorylation deficiency 444458 type 24 Cognitive impairment-coarse facies-heart defects444077 obesity-pulmonary involvement-short statureskeletal dysplasia syndrome Cataract-growth hormone deficiency-sensory 436174 neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome Colobomatous optic disc-macular atrophy435930 chorioretinopathy syndrome X-linked microcephaly-growth retardation435938 prognathism-cryptorchidism syndrome Progeroid features-hepatocellular carcinoma 435953 predisposition syndrome Severe intellectual disability-epilepsy-cataract 438178 syndrome due to fatty acyl-CoA reductase 1 deficiency Autosomal recessive primary immunodeficiency 437552 with defective spontaneous natural killer cell cytotoxicity Multiple epiphyseal dysplasia, with severe 166029 proximal femoral dysplasia Osteogenesis imperfecta - retinopathy - seizures 2773 intellectual disability 1488 Cooper-Jabs syndrome Gonadal dysgenesis, XY type - associated 1770 anomalies

Number of cases

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

3 Cases 3 Cases 3 Cases 3 Cases 3 Cases

3 Cases 3 Cases 2 Cases 2 Cases 2 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

41

ORPHA Number

Disease or Group of diseases

Number of cases

1046 Lethal hemolytic anemia - genital anomalies 2 Cases Hypogonadism - mitral valve prolapse - intellectual 2233 2 Cases disability Mitochondrial DNA depletion syndrome, 1933 encephalomyopathic form with methylmalonic 2 Cases aciduria 2135 Hennekam-Beemer syndrome 2 Cases 1422 Chondrodysplasia - disorder of sex development 2 Cases Multiple sclerosis - ichthyosis - factor VIII 3151 deficiency 1948 Epilepsy - microcephaly - skeletal dysplasia 1354 Heart defects - limb shortening 949

Acrocraniofacial dysostosis

2 Cases 2 Cases 2 Cases 2 Cases

1227 Bangstad syndrome 1237 Beemer-Ertbruggen syndrome

2 Cases

1326 Camptodactyly syndrome, Guadalajara type 2 Brachytelephalangy - dysmorphism - Kallmann 1295 syndrome 1021 Amaurosis-hypertrichosis syndrome 1068 Aniridia-intellectual disability syndrome

2 Cases

2 Cases

2 Cases 2 Cases 2 Cases

1064 Aniridia - renal agenesis - psychomotor retardation 2 Cases 1003 Scalp defects - postaxial polydactyly 2 Cases Alopecia-intellectual disability-hypergonadotropic 2 Cases hypogonadism syndrome 1659 Dermatoleukodystrophy 2 Cases 1806 Ectodermal dysplasia - blindness 2 Cases 1014

Dandy-Walker malformation - postaxial polydactyly 1563 Dahlberg-Borer-Newcomer syndrome Cryptomicrotia - brachydactyly - excess fingertip 1547 arch 1533 Craniosynostosis - fibular aplasia 1380 Cataract - nephropathy - encephalopathy 1566

1368 Cataract - ataxia - deafness Contractures - ectodermal dysplasia - cleft 1484 lip/palate 1453 Cleidorhizomelic syndrome 1433 Choroidal atrophy - alopecia Hypogonadotropic hypogonadism - retinitis pigmentosa Male hypergonadotropic hypogonadism 2234 intellectual disability - skeletal anomalies Hyposmia - nasal and ocular hypoplasia 2250 hypogonadotropic hypogonadism 2249 Ulna hypoplasia - intellectual disability 2266 Hypotrichosis-intellectual disability, Lopes type 2235

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

2 Cases 2272 Ichthyosis - oral and digital anomalies 2 Cases 2271 Congenital ichthyosis - microcephalus - tetraplegia 2 Cases Ichthyosis - hepatosplenomegaly - cerebellar 2274 2 Cases degeneration

ORPHA Number

Disease or Group of diseases

Dysmorphism - short stature - deafness - disorder of sex development 2155 Hirschsprung disease - deafness - polydactyly Microcephaly - glomerulonephritis - marfanoid 2172 habitus 2181 Hydrocephaly - tall stature - joint laxity 2119 HEC syndrome 2282

Number of cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

1995 Cleft lip - retinopathy Alar cartilages hypoplasia-coloboma-telecanthus 2007 syndrome 2010 Cleft palate - stapes fixation - oligodontia 2025 Gingival fibromatosis - facial dysmorphism

2 Cases

2718 Oculotrichodysplasia 2513 Microcephaly - albinism - digital anomalies

2 Cases

2511 Microbrachycephaly - ptosis - cleft lip 2390 Lichstenstein syndrome

2 Cases

2347 Lethal Kniest-like dysplasia 2324 Kaler-Garrity-Stern syndrome

2 Cases

3177 Corneal-cerebellar syndrome 3199 Stimmler syndrome

2 Cases

3134 SCARF syndrome Spastic tetraplegia - retinitis pigmentosa 3011 intellectual disability 46,XX disorder of sex development - skeletal 2975 anomalies Pterygium colli - intellectual disability - digital 2988 anomalies 2985 Pseudoprogeria syndrome 2888 Pierre Robin syndrome - faciodigital anomaly

2 Cases

2867 Short stature, Brussels type 2876 PHAVER syndrome

2 Cases

2892 Pilodental dysplasia - refractive errors 2825 PARC syndrome

2 Cases

2826 Spastic paraplegia - precocious puberty 3262 Syngnathia multiple anomalies

2 Cases

3291 Teebi-Shaltout syndrome 3323 Thrombocytopenia - Robin sequence

2 Cases

3327 Thyrocerebrorenal syndrome Deafness - genital anomalies - metacarpal and 3224 metatarsal synostosis 3239 Deafness - vitiligo - achalasia 3365 Trigonocephaly - broad thumbs

2 Cases

3368 Trigonocephaly - bifid nose - acral anomalies 3200 Stoll-Alembik-Finck syndrome

2 Cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

2 Cases Deaf blind hypopigmentation syndrome, Yemenite 3214 2 Cases type 3105 Robinow-like syndrome 2 Cases 3132 Say-Barber-Miller syndrome 2 Cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

2 Cases 2 Cases 2 Cases 2 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

42

ORPHA Number

Disease or Group of diseases

3167 Siegler-Brewer-Carey syndrome 2352 Kozlowski-Brown-Hardwick syndrome Microcephaly - seizures - intellectual disability heart disease Osteochondrodysplatic nanism - deafness 2653 retinitis pigmentosa Adult familial nephronophthisis - spastic 2666 quadriparesia 1485 Arthrogryposis - hyperkeratosis, lethal form 2729 Okamoto syndrome 2519

Atherosclerosis - deafness - diabetes - epilepsy nephropathy 2015 Cleft palate - short stature - vertebral anomalies 2427 Macrocephaly - short stature - paraplegia 1192

2898 X-linked intellectual disability - plagiocephaly 2183 Hydrocephalus - obesity - hypogonadism 3240 69088 71278 73224 73230 73245 73246 71270 71267 50812 50817

Number of cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

Central nervous system calcification - deafness 2 Cases tubular acidosis - anemia Anhidrotic ectodermal dysplasiaimmunodeficiency-osteopetrosis-lymphedema 2 Cases syndrome Congenital brain dysgenesis due to glutamine 2 Cases synthetase deficiency Tubular renal disease - cardiomyopathy 2 Cases Ossification anomalies - psychomotor 2 Cases development delay Spinal muscular atrophy - Dandy-Walker 2 Cases malformation - cataracts Visceral neuropathy - brain anomalies - facial 2 Cases dysmorphism - developmental delay Auriculoocular anomalies - cleft lip 2 Cases Dentinogenesis imperfecta - short stature - hearing 2 Cases loss - intellectual disability Zellweger-like syndrome without peroxisomal 2 Cases anomalies Duane anomaly - myopathy - scoliosis 2 Cases

50809 Talo-patello-scaphoid osteolysis 50810 Microlissencephaly - micromelia

2 Cases

52047 Braddock syndrome Agenesis of the corpus callosum-intellectual 52055 disability-coloboma-micrognathia syndrome 64542 Acrofacial dysostosis, Kennedy-Teebi type 79302 Congenital bile acid synthesis defect type 3

2 Cases

79332 B4GALT1-CDG Brain malformation - congenital heart disease 75389 postaxial polydactyly Developmental malformations - deafness 79107 dystonia Neonatal diabetes - congenital hypothyroidism 79118 congenital glaucoma - hepatic fibrosis - polycystic kidneys

2 Cases

2 Cases

2 Cases 2 Cases 2 Cases

2 Cases 2 Cases 2 Cases

ORPHA Number

Disease or Group of diseases

Not NOTCH3-related small vessel disease of the brain Auricular abnormalities - cleft lip with or without 77300 cleft palate - ocular abnormalities Osteopenia - myopia - hearing loss - intellectual 91133 disability - facial dysmorphism 91130 Cardiomyopathy - hypotonia - lactic acidosis 91494 Macular coloboma-cleft palate-hallux valgus 77304

Obesity - colitis - hypothyroidism - cardiac 88643 hypertrophy - developmental delay 90022 Cardiomyopathy - renal anomalies X-linked intellectual disability - acromegaly 85327 hyperactivity 86822 Lissencephaly type 3 - metacarpal bone dysplasia Hypercoagulability syndrome due to 83639 glycosylphosphatidylinositol deficiency X-linked intellectual disability - epilepsy 85319 progressive joint contractures - dysmorphism Familial papillary thyroid carcinoma with renal 97290 papillary neoplasia 95428 COG8-CDG Severe intellectual disability-epilepsy-anal 94066 anomalies-distal phalangeal hypoplasia 139414 Congenital panfollicular nevus Microcephaly - digital anomalies - intellectual 137653 disability Lung fibrosis - immunodeficiency - 46,XX gonadal 137631 dysgenesis 103912 Epithelio-exfoliative colitis - deafness Resistance to thyrotropin-releasing hormone 99832 syndrome Univentricular heart with single atrio-ventricular 99069 valve 217399 Congenital insensitivity to pain with hyperhidrosis 238523 Atypical hypotonia - cystinuria syndrome 238505 Autosomal recessive lymphoproliferative disease Severe X-linked mitochondrial 238329 encephalomyopathy Late-onset localized junctional epidermolysis 231556 bullosa - intellectual disability Autosomal recessive ataxia due to PEX10 247815 deficiency Leukoencephalopathy - dystonia - motor 163684 neuropathy 163985 Hyperekplexia - epilepsy Hypospadias - hypertelorism - coloboma and 157788 deafness Hereditary cryohydrocytosis with reduced 168577 stomatin Fatal mitochondrial disease due to combined 168566 oxidative phosphorylation deficiency 3 168555 Spondylometaphyseal dysplasia, A4 type

Number of cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

43

ORPHA Number

Disease or Group of diseases

Brain demyelination due to methionine adenosyltransferase deficiency 169100 Immunodeficiency due to CD25 deficiency 166038 Metaphyseal chondrodysplasia, Kaitila type 168598

Metaphyseal chondrodysplasia - retinitis pigmentosa FASTKD2-related infantile mitochondrial 166105 encephalomyopathy Spondyloepimetaphyseal dysplasia - abnormal 168451 dentition Spondyloepimetaphyseal dysplasia, Geneviève 168454 type Spondylometaphyseal dysplasia - bowed forearms 168552 - facial dysmorphism 183707 Neutrophil immunodeficiency syndrome 199348 Thiamine-responsive encephalopathy 166035

Number of cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

Disease or Group of diseases

Congenital chronic diarrhea with protein-losing enteropathy Intellectual disability - craniofacial dysmorphism 329224 cryptorchidism 324575 Hyperinsulinism due to HNF1A deficiency Congenital ichthyosis-intellectual disability-spastic 352333 quadriplegia syndrome 261304 Paternal 20q13.2q13.3 microdeletion syndrome 261534 49,XXXYY syndrome 329242

Number of cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

2 Cases

263501 COG4-CDG 263463 CHST3-related skeletal dysplasia

2 Cases

2 Cases

276556 Hyperinsulinism due to UCP2 deficiency 276405 Hyperbiliverdinemia 280071 ALG11-CDG 280576 Nestor-Guillermo progeria syndrome

2 Cases

280397 Familial Alzheimer-like prion disease 280663 Hermansky-Pudlak syndrome type 9

2 Cases

281127 Acral self-healing collodion baby 397725 COASY protein-associated neurodegeneration

2 Cases

2 Cases 2 Cases

199329 Congenital myopathy, Paradas type 293807 Ketamine-induced biliary dilatation

2 Cases

294026 2q31.1 microduplication syndrome 294023 Neonatal inflammatory skin and bowel disease

2 Cases

313772 Early-onset spastic ataxia-neuropathy syndrome 306511 Autosomal recessive spastic paraplegia type 48

2 Cases

313947 2q23.1 microduplication syndrome Contractures-webbed neck-micrognathia314002 hypoplastic nipples syndrome 314034 7p22.1 microduplication syndrome 314029 High bone mass osteogenesis imperfecta

2 Cases

2 Cases

2 Cases 2 Cases 2 Cases 2 Cases

2 Cases

2 Cases Autosomal dominant Charcot-Marie-Tooth disease 397735 2 Cases type 2U 231531 Hermansky-Pudlak syndrome type 7 2 Cases 2575 Cystic fibrosis - gastritis - megaloblastic anemia 2 Cases 412217 Dystonia-aphonia syndrome 2 Cases

2 Cases

412181

2 Cases 2 Cases

2 Cases

Marfanoid habitus - inguinal hernia - advanced 2 Cases bone age 314629 CLN11 disease 2 Cases Intellectual disability-hypotonia-brachycephaly314575 2 Cases pyloric stenosis-cryptorchidism syndrome Autoinflammation-PLCG2-associated antibody 324530 2 Cases deficiency-immune dysregulation Aphonia - deafness - retinal dystrophy - bifid 324540 2 Cases halluces - intellectual disability Muscular hypertrophy - hepatomegaly 324416 2 Cases polyhydramnios X-linked intellectual disability - cardiomegaly 324410 2 Cases congestive heart failure 324307 Severe lateral tibial bowing with short stature 2 Cases Multiple paragangliomas associated with 324299 2 Cases polycythemia T-cell immunodeficiency with epidermodysplasia 324294 2 Cases verruciformis Mendelian susceptibility to mycobacterial diseases 319600 2 Cases due to partial IRF8 deficiency Autosomal dominant mendelian susceptibility to 319589 mycobacterial diseases due to partial IFNgammaR2 2 Cases deficiency Spondylocostal dysostosis - hypospadias 329252 2 Cases intellectual disability 314041

ORPHA Number

Epidermolysis bullosa simplex due to BP230 deficiency Autosomal recessive cerebellar ataxia-epilepsy404499 intellectual disability syndrome due to KIAA0226 deficiency Global developmental delay-lung cysts404476 overgrowth-Wilms tumor syndrome 401862 Lipoyl transferase 1 deficiency 401923 9q31.1q31.3 microdeletion syndrome

2 Cases 2 Cases 2 Cases 2 Cases

2 Cases Partial corpus callosum agenesis-cerebellar vermis 401959 2 Cases hypoplasia with posterior fossa cysts syndrome 401764 Pancytopenia-developmental delay syndrome 2 Cases 401805 Autosomal recessive spastic paraplegia type 63 2 Cases 401815 Autosomal recessive spastic paraplegia type 66 2 Cases 401820 Autosomal recessive spastic paraplegia type 67 401830 Autosomal recessive spastic paraplegia type 69

2 Cases

397959 TCR-alpha-beta-positive T-cell deficiency 397946 Autosomal recessive spastic paraplegia type 58

2 Cases

2 Cases 2 Cases

Intellectual disability-obesity-prognathism-eye and 2 Cases skin anomalies syndrome Finger hyperphalangy-toe anomalies-severe pectus 369979 2 Cases excavatum syndrome Methylmalonic acidemia with homocystinuria, 369955 2 Cases type cblJ Aldosterone-producing adenoma with seizures and 369929 2 Cases neurological abnormalities 397973

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

44

ORPHA Number

Disease or Group of diseases

Early infantile epileptic encephalopathy without suppression burst 369881 2p21 microdeletion syndrome without cystinuria 370921 STT3A-CDG 369894

370039 Angora hair nevus 370015 Spondyloepimetaphyseal dysplasia, Isidor type

Number of cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

Spondylometaphyseal dysplasia, Czarny-Ratajczak 2 Cases type 363680 2p13.2 microdeletion syndrome 2 Cases Autosomal recessive limb-girdle muscular 363623 2 Cases dystrophy type 2T Autosomal recessive limb-girdle muscular 363543 2 Cases dystrophy type 2R Severe combined immunodeficiency due to 357237 2 Cases CARD11 deficiency Mandibulofacial dysostosis - macroblepharon 357158 2 Cases macrostomia Hypotonia-cerebral atrophy-hyperglycinemia 363424 2 Cases syndrome Corneal intraepithelial dyskeratosis-palmoplantar 352662 2 Cases hyperkeratosis-laryngeal dyskeratosis syndrome Intellectual disability - obesity - brain 352530 2 Cases malformations - facial dysmorphism Infantile hypertrophic cardiomyopathy due to 352563 2 Cases MRPL44 deficiency 370930 XYLT1-CDG 2 Cases Muscle-eye-brain disease with bilateral multicystic 370997 2 Cases leucodystrophy 391343 Fatal post-viral neurodegenerative disorder 2 Cases Growth and developmental delay-hypotonia-vision 391348 2 Cases impairment-lactic acidosis syndrome Growth retardation-mild developmental delay391366 2 Cases chronic hepatitis syndrome 420741 RIDDLE syndrome 2 Cases Combined oxidative phosphorylation deficiency 420728 2 Cases type 20 Autosomal recessive severe congenital 420699 2 Cases neutropenia due to CXCR2 deficiency 439232 AApoAIV amyloidosis 2 Cases Combined oxidative phosphorylation deficiency 420733 2 Cases type 21 424107 Congenital myopathy with myasthenic-like onset 2 Cases Microcephaly-short stature-intellectual disability423306 2 Cases facial dysmorphism syndrome X-linked intellectual disability-limb spasticity423479 2 Cases retinal dystrophy-diabetes insipidus syndrome Autosomal dominant Charcot-Marie-Tooth disease 435819 2 Cases type 2 due to TFG mutation 431329 Autosomal recessive spastic paraplegia type 57 2 Cases 398109 Neonatal autoimmune hemolytic anemia 2 Cases 370019

440713 Isolated sedoheptulokinase deficiency 436182 Microcephalic primordial dwarfism-insulin

ORPHA Number

Disease or Group of diseases

resistance syndrome Lethal fetal cerebrorenogenitourinary 439897 agenesis/hypoplasia syndrome 435660 LIPE-related familial partial lipodystrophy Severe autosomal recessive 438207 macrothrombocytopenia Progressive encephalopathy with leukodystrophy 431361 due to DECR deficiency 440731 L-ferritin deficiency 443950 Charcot-Marie-Tooth disease type 2T

Number of cases

2 Cases 2 Cases 2 Cases 2 Cases 2 Cases

2 Cases Limb-girdle muscular dystrophy due to POMK 445110 2 Cases deficiency 166032 Multiple epiphyseal dysplasia, with miniepiphyses 2 Cases 79326 ALG2-CDG 1 Case Glycogen storage disease due to muscle beta99849 1 Case enolase deficiency 243343 Dimethylglycine dehydrogenase deficiency 1 Case 238459 SLC35A1-CDG 1 Case Autosomal recessive intermediate Charcot-Marie1 Case Tooth disease type B 250977 AICA-ribosiduria 1 Case 300536 DDOST-CDG 1 Case 324422 ALG13-CDG 1 Case 254334

330029 Hypotrichosis-deafness syndrome Lethal encephalopathy due to mitochondrial and 330050 peroxisomal fission defect Transient neonatal multiple acyl-CoA 329942 dehydrogenase deficiency Glycogen storage disease due to glycogenin 263297 deficiency 263494 DPM3-CDG Spinal muscular atrophy with respiratory distress 404521 type 2 411712 Maternal riboflavin deficiency 401800 Autosomal recessive spastic paraplegia type 60

1 Case

401825 Autosomal recessive spastic paraplegia type 68 401840 Autosomal recessive spastic paraplegia type 71

1 Case

397968 Charcot-Marie-Tooth disease type 2R 370924 STT3B-CDG

1 Case

370097 Oculocutaneous albinism type 6 370927 SSR4-CDG

1 Case

440706 Ribose-5-P isomerase deficiency 435934 COG2-CDG

1 Case

Combined immunodeficiency due to OX40 431149 deficiency 435651 CIDEC-related familial partial lipodystrophy

1 Case 1 Case 1 Case 1 Case 1 Case 1 Case 1 Case 1 Case 1 Case 1 Case 1 Case 1 Case 1 Case

2 Cases 2 Cases

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

45

Number of published families ORPHA Number

Disease or Group of diseases

Number of families

250 1652 Dent disease Families 100 1949 Benign familial neonatal epilepsy Families 100 1416 Familial calcium pyrophosphate deposition Families 100 89843 Dystrophic epidermolysis bullosa pruriginosa Families 100 98759 Spinocerebellar ataxia type 17 Families Autosomal dominant nocturnal frontal lobe 100 98784 epilepsy Families 81 2524 Pontocerebellar hypoplasia type 2 Families 80 757 Pseudohypoaldosteronism type 2 Families 52 60030 Loeys-Dietz syndrome Families 50 627 Nance-Horan syndrome Families 50 2526 Microcephaly - lymphedema - chorioretinopathy Families 50 98934 Huntington disease-like 2 Families 46,XY disorder of sex development due to 550 753 alpha-reductase 2 deficiency Families 40 2254 Pontocerebellar hypoplasia type 1 Families 40 79410 Pretibial dystrophic epidermolysis bullosa Families 40 98762 Spinocerebellar ataxia type 12 Families 40 263548 Peeling skin syndrome type A Families 35 1106 Microphthalmia with limb anomalies Families 35 79501 Punctate palmoplantar keratoderma type 1 Families 35 163937 X-linked intellectual disability, Najm type Families 35 200418 Immunodeficiency with factor I anomaly Families Autosomal recessive axonal neuropathy with 33 324442 neuromyotonia Families Glycogen storage disease due to 30 713 phosphoglycerate kinase 1 deficiency Families Camptodactyly-arthropathy-coxa-vara30 2848 pericarditis syndrome Families 30 425 Apolipoprotein A-I deficiency Families Phosphoribosylpyrophosphate synthetase 30 3222 superactivity Families 3237 Multiple synostoses syndrome 30

ORPHA Number

Disease or Group of diseases

Number of families

Families 30 90026 Primary erythermalgia Families Hereditary combined deficiency of vitamin K30 98434 dependent clotting factors Families 30 217012 Spinocerebellar ataxia type 31 Families MITF-related melanoma and renal cell carcinoma 30 293822 predisposition syndrome Families 30 263553 Peeling skin syndrome type B Families 28 33108 Lethal multiple pterygium syndrome Families Familial hyperthyroidism due to mutations in TSH 28 424 receptor Families 24 85293 X-linked intellectual disability, Cabezas type Families 20 643 Giant axonal neuropathy Families 20 959 Acro-renal-ocular syndrome Families Dilated cardiomyopathy - hypergonadotropic 20 2229 hypogonadism Families 20 3203 Overhydrated hereditary stomatocytosis Families Familial platelet syndrome with predisposition to 20 71290 acute myelogenous leukemia Families 20 98763 Spinocerebellar ataxia type 14 Families 20 97286 Carney-Stratakis syndrome Families 20 100998 Autosomal dominant spastic paraplegia type 17 Families 20 99027 Adult-onset autosomal dominant leukodystrophy Families 20 3202 Dehydrated hereditary stomatocytosis Families 19 99791 Dentin dysplasia type II Families Non-spherocytic hemolytic anemia due to 17 90031 hexokinase deficiency Families Infantile-onset ascending hereditary spastic 17 293168 paralysis Families 16 88621 Ichthyosis prematurity syndrome Families 16 84090 Fibronectin glomerulopathy Families 15 2950 Triphalangeal thumb - polysyndactyly syndrome Families 15 25980 X-linked myopathy with excessive autophagy Families X-linked distal arthrogryposis multiplex 14 1145 congenita Families X-linked intellectual disability - cerebellar 12 137831 hypoplasia Families

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

46

ORPHA Number

Disease or Group of diseases

Number of families

12 Families 12 401996 Karyomegalic interstitial nephritis Families 11 93974 Smith-Fineman-Myers syndrome Families 11 99955 Charcot-Marie-Tooth disease type 4B1 Families 11 98971 Posterior amorphous corneal dystrophy Families 11 439218 KCNQ2-related epileptic encephalopathy Families 10 931 Acheiropodia Families 10 1276 Brachydactyly-arterial hypertension syndrome Families 10 1062 Hereditary neurocutaneous angioma Families 10 1412 Tarsal-carpal coalition syndrome Families 10 2238 Familial isolated hypoparathyroidism Families Palmoplantar keratoderma-esophageal 10 2198 carcinoma syndrome Families 10 2202 Palmoplantar keratoderma-deafness syndrome Families 10 2791 Otodental syndrome Families 10 3412 VACTERL with hydrocephalus Families 10 90001 X-linked cone dysfunction syndrome with myopia Families Syndromic X-linked intellectual disability due to 10 85279 JARID1C mutation Families 10 140927 Benign familial neonatal-infantile seizures Families 10 100994 Autosomal dominant spastic paraplegia type 13 Families 10 100993 Autosomal dominant spastic paraplegia type 12 Families 10 100991 Autosomal dominant spastic paraplegia type 10 Families 10 100989 Autosomal dominant spastic paraplegia type 8 Families 10 100988 Autosomal dominant spastic paraplegia type 6 Families 10 101006 Autosomal recessive spastic paraplegia type 26 Families 10 100996 Autosomal recessive spastic paraplegia type 15 Families 10 158673 Acral dystrophic epidermolysis bullosa Families 10 158676 Dystrophic epidermolysis bullosa, nails only Families 228277 Familial anetoderma

ORPHA Number

Disease or Group of diseases

166063 Pontocerebellar hypoplasia type 4 Hereditary proximal myopathy with early respiratory failure Xeroderma pigmentosum complementation 276252 group B Autosomal recessive cerebellar ataxia due to 412057 STUB1 deficiency 71291 Hereditary vascular retinopathy 100008 ACys amyloidosis 178464

Number of families

10 Families 10 Families 10 Families 10 Families 9 Families 9 Families

217266 BNAR syndrome 1377 Cataract-microcornea syndrome

9 Families

1832 Lethal osteosclerotic bone dysplasia 66629 Goldberg-Shprintzen megacolon syndrome Autosomal recessive intermediate Charcot217055 Marie-Tooth disease type A 306527 Isolated hereditary congenital facial paralysis 1897 EEM syndrome

8 Families

1777 Temtamy syndrome 100990 Autosomal dominant spastic paraplegia type 9

7 Families

251274 Familial hyperaldosteronism type III Autosomal recessive systemic lupus 300345 erythematosus 329457 Distal arthrogryposis type 5D 281139 Annular epidermolytic ichthyosis

7 Families

Foveal hypoplasia-optic nerve decussation 397618 defect-anterior segment dysgenesis syndrome 93561 ALys amyloidosis 1799 Familial developmental dysphasia

8 Families 8 Families 8 Families 8 Families 7 Families 7 Families

7 Families 7 Families 7 Families 7 Families 7 Families 6 Families

79503 Ichthyosis hystrix of Curth-Macklin 79401 Epidermolysis bullosa simplex, Ogna type

6 Families

75381 Cystoid macular dystrophy Deafness with labyrinthine aplasia, microtia, and 90024 microdontia X-linked reticulate pigmentary disorder with 85453 systemic manifestations 140917 Stapes ankylosis with broad thumbs and toes 137634 Overgrowth - macrocephaly - facial dysmorphism

6 Families

Mesoaxial synostotic syndactyly with phalangeal 157801 reduction Hypopigmentation-punctate palmoplantar 324561 keratoderma syndrome 391411 Atypical juvenile parkinsonism 2118 Hawkinsinuria

6 Families

6 Families 6 Families 6 Families 6 Families 6 Families 6 Families 6 Families 5 Families

1428 Familial chondromalacia patellae 1836 Mesomelic dysplasia, Kantaputra type

5 Families

2802 X-linked sideroblastic anemia and ataxia 3248 Distal symphalangism

5 Families

3351 Trichodental syndrome

5 Families

5 Families 5 Families

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

47

ORPHA Number

Disease or Group of diseases

Intellectual disability-developmental delaycontractures syndrome Familial primary hypomagnesemia with 34527 normocalciuria and normocalcemia Autosomal dominant limb-girdle muscular 34517 dystrophy type 1E Autosomal dominant limb-girdle muscular 34516 dystrophy type 1D Short stature - pituitary and cerebellar defects 85442 small sella turcica Familial encephalopathy with neuroserpin 85110 inclusion bodies X-linked hereditary sensory and autonomic 139583 neuropathy with deafness Female restricted epilepsy with intellectual 101039 disability 101068 Congenital stromal corneal dystrophy Autosomal dominant Charcot-Marie-Tooth 99940 disease type 2F 231108 Familial rhabdoid tumor 178333 Åland Islands eye disease 3454

Number of families

ORPHA Number

5 Families

423296 Spinocerebellar ataxia type 38 399103 Nebulin-related early-onset distal myopathy

4 Families 4 Families

5 Families 5 Families

2211

5 Families 5 Families 5 Families 5 Families 5 Families 5 Families

Hypertelorism - hypospadias - polysyndactyly syndrome 2699 Median nodule of the upper lip Adducted thumbs-arthrogryposis syndrome, 2952 Christian type 3421 Cerebroretinal vasculopathy 3466 WT limb-blood syndrome 2066 162 67045 67044

5 Families Autism-epilepsy syndrome due to branched chain 308410 5 Families ketoacid dehydrogenase kinase deficiency Ocular albinism with congenital sensorineural 352740 5 Families deafness 1879 Melorheostosis with osteopoikilosis 5 Families 391330 X-linked osteoporosis with fractures 5 Families

67036

Colobomatous microphthalmia-rhizomelic dysplasia syndrome Autoimmune interstitial lung disease-arthritis 444092 syndrome 86789 Patella aplasia/hypoplasia 1275 Brachydactyly - elbow wrist dysplasia

Number of families

1252 Blepharonasofacial malformation syndrome 3 Families 1266 Dermato-cardio-skeletal syndrome, Borrone type 3 Families 1074 Ankyloblepharon filiforme - imperforate anus 3 Families

5 Families

5 Families

424099

Disease or Group of diseases

5 Families 5 Families 5 Families 4 Families

2307 IVIC syndrome 2947 Triphalangeal thumbs - brachyectrodactyly

4 Families

46348 Paroxysmal extreme pain disorder 77297 Majeed syndrome

4 Families

97239 Reducing body myopathy 101108 Spinocerebellar ataxia type 23

4 Families

98890 Early-onset X-linked isolated optic atrophy Progressive sensorineural hearing loss 228012 hypertrophic cardiomyopathy 171851 MEDNIK syndrome 293936 EDICT syndrome

4 Families

4 Families 4 Families 4 Families

4 Families 4 Families 4 Families

Facial dysmorphism-lens dislocation-anterior 412022 segment abnormalities-spontaneous filtering 4 Families blebs syndrome AXIN2-related attenuated familial adenomatous 401911 4 Families polyposis Hyperuricemia-pulmonary hypertension-renal 363694 4 Families failure-alkalosis syndrome

Gamma-aminobutyric acid transaminase deficiency Cataract-glaucoma X-linked intellectual disability with isolated growth hormone deficiency Thrombocytopenia with congenital dyserythropoietic anemia Autosomal dominant optic atrophy and cataract

3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families

98870 Congenital dyserythropoietic anemia type III 98766 Spinocerebellar ataxia type 5

3 Families

97249 Pontocerebellar hypoplasia type 3 Autosomal recessive cerebellar ataxia - blindness 95433 - deafness 94064 Deafness-infertility syndrome 101010 Autosomal recessive spastic paraplegia type 30

3 Families

Autosomal dominant Charcot-Marie-Tooth 99944 disease type 2K 157832 Craniorhiny PLCG2-associated antibody deficiency and 300359 immune dysregulation 314978 X-linked non progressive cerebellar ataxia Hereditary thrombocytosis with transverse limb 329319 defect 276193 Spinocerebellar ataxia type 35 Familial progressive hyper- and 280628 hypopigmentation Autosomal dominant Charcot-Marie-Tooth 401964 disease type 2 with giant axons Short stature-advanced bone age-early onset 435804 osteoarthritis syndrome 444072 Cerebellar-facial-dental syndrome Maternally-inherited cardiomyopathy and 1349 hearing loss Retinitis pigmentosa - intellectual disability 3085 deafness - hypogenitalism Congenital absence/hypoplasia of fingers 973 excluding thumb, unilateral 1241 Bencze syndrome 114 Auriculoosteodysplasia

3 Families

3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 3 Families 2 Families 2 Families 2 Families 2 Families 2 Families

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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ORPHA Number

Disease or Group of diseases

Number of families

1187 Lethal ataxia with deafness and optic atrophy 1867 Bullous dystrophy, macular type

2 Families

1350 Heart-hand syndrome type 2 1436 Skeletal dysplasia - intellectual disability

2 Families

Familial isolated hypoparathyroidism due to agenesis of parathyroid gland 2027 Gingival fibromatosis - progressive deafness 2754 Joubert syndrome with orofaciodigital defect 2239

2504 2405 2818 42665 266 63261 55596 79141

Metaphyseal dysplasia - maxillary hypoplasia brachydacty Thickened earlobes - conductive deafness Spastic paraplegia - glaucoma - intellectual disability Tietz syndrome Autosomal dominant limb-girdle muscular dystrophy type 1A HERNS syndrome Autosomal dominant limb-girdle muscular dystrophy type 1G Hereditary painful callosities

2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families

79136 Episodic ataxia type 4 75497 X-linked Ehlers-Danlos syndrome

2 Families

75327 North Carolina macular dystrophy 75373 Progressive bifocal chorioretinal atrophy

2 Families

Alport syndrome-intellectual disability-midface 86818 hypoplasia-elliptocytosis syndrome 85287 X-linked intellectual disability, Siderius type 94083 Partington syndrome

2 Families 2 Families 2 Families 2 Families 2 Families

93409 Brachydactyly-syndactyly, Zhao type 93389 Brachydactyly type A5

2 Families

139471 Microphthalmia with brain and digit anomalies 139480 Autosomal recessive spastic paraplegia type 39

2 Families

Hereditary sensory and autonomic neuropathy 139564 type 1B 101007 Autosomal recessive spastic paraplegia type 27 Sensorineural deafness with dilated 217622 cardiomyopathy 300576 Oligodontia - cancer predisposition syndrome Tall stature - scoliosis - macrodactyly of the great 329191 toes Spectrin-associated autosomal recessive 352403 cerebellar ataxia 439254 ITM2B amyloidosis 434179 Orofaciodigital syndrome type 14 998

Albinism-deafness syndrome

1876 Oculogastrointestinal muscular dystrophy 1228 Banki syndrome

2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 2 Families 1 Family 1 Family 1 Family

1319 Camptobrachydactyly 1 Family 1144 Arthrogryposis-like hand anomaly - sensorineural 1 Family

ORPHA Number

Disease or Group of diseases

deafness Lipodystrophy due to peptidic growth factors 1979 deficiency Steroid dehydrogenase deficiency - dental 3196 anomalies 1765 Dyschondrosteosis - nephritis 1527 Craniosynostosis, Philadelphia type Woolly hair - hypotrichosis - everted lower lip 1409 outstanding ears 2186 Hydrocephalus - blue sclerae - nephropathy 2709 Oculodental syndrome, Rutherfurd type

Number of families

1 Family 1 Family 1 Family 1 Family 1 Family 1 Family 1 Family

2674 Cyprus facial-neuromusculoskeletal syndrome 2391 Congenitally short costocoracoid ligament

1 Family

2999 Ptosis - strabismus - ectopic pupils 2890 Pili torti - onychodysplasia

1 Family

2917 Polydactyly-myopia syndrome 3408 Upington disease

1 Family

3417 Van den Bosch syndrome 1246 Brachydactyly - nystagmus - cerebellar ataxia

1 Family

52056 Ulnar/fibula ray defect - brachydactyly Autosomal dominant limb-girdle muscular 55595 dystrophy type 1F 79135 Episodic ataxia type 3 79129 Trichodysplasia - amelogenesis imperfecta

1 Family

75501 Ehlers-Danlos syndrome, fibronectinemic type 79085 AKT2-related familial partial lipodystrophy

1 Family

93283 Spondyloepiphyseal dysplasia, Kimberley type 85335 Fried syndrome

1 Family

85322 X-linked intellectual disability, Pai type X-linked recessive intellectual disability 83648 macrocephaly - ciliary dysfunction 85168 Craniofacial conodysplasia 85292 X-linked spinocerebellar ataxia type 4

1 Family

X-linked intellectual disability, Stocco Dos Santos 85288 type Autosomal recessive cerebellar ataxia - saccadic 95434 intrusion 93397 Brachydactyly type A7 Microtia-eye coloboma-imperforation of the 139450 nasolacrimal duct 139512 Neuropathy with hearing impairment 101101 Charcot-Marie-Tooth disease type 2B2

1 Family 1 Family 1 Family 1 Family

1 Family 1 Family 1 Family 1 Family 1 Family

1 Family 1 Family 1 Family 1 Family 1 Family 1 Family 1 Family 1 Family 1 Family

101112 Spinocerebellar ataxia type 26 100995 Autosomal recessive spastic paraplegia type 14

1 Family

101005 Autosomal recessive spastic paraplegia type 25 101003 Autosomal recessive spastic paraplegia type 23

1 Family

1 Family 1 Family

101004 Autosomal recessive spastic paraplegia type 24 1 Family 100999 Autosomal dominant spastic paraplegia type 19 1 Family 100997 X-linked spastic paraplegia type 16 1 Family

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

49

ORPHA Number

Disease or Group of diseases

101009 Autosomal dominant spastic paraplegia type 29 Autosomal dominant Charcot-Marie-Tooth 99941 disease type 2G Autosomal dominant Charcot-Marie-Tooth 99945 disease type 2L 99806 Oculootodental syndrome 98959 Subepithelial mucinous corneal dystrophy

Number of families

1 Family 1 Family 1 Family 1 Family 1 Family

Epibulbar lipodermoid - preauricular appendage 1 Family polythelia 163662 Spondyloepiphyseal dysplasia, Reardon type 1 Family 163988 Developmental delay - deafness, Hildebrand type 1 Family 231742

Spondyloepimetaphyseal dysplasia, matrilin-3 type 166011 Multiple epiphyseal dysplasia, Beighton type 166108 Intellectual disability, Birk-Barel type 156728

1 Family 1 Family

1 Family 178461 X-linked myopathy with postural muscle atrophy 1 Family 171617 Autosomal dominant spastic paraplegia type 38 1 Family 171622 Autosomal recessive spastic paraplegia type 32 1 Family 171629 Autosomal recessive spastic paraplegia type 35 293375 Grayson-Wilbrandt corneal dystrophy

1 Family

300305 11p15.4 microduplication syndrome Autosomal dominant proximal renal tubular 314889 acidosis 329883 Non-hypoproteinemic hypertrophic gastropathy 329475 Spastic paraplegia - Paget disease of bone

1 Family

370091 Oculocutaneous albinism type 5 X-linked dyserythropoetic anemia with abnormal 363727 platelets and neutropenia 391320 East Texas bleeding disorder 391327 X-linked calvarial hyperostosis

1 Family

1 Family

1 Family 1 Family

1 Family Autoimmune lymphoproliferative syndrome with 275517 1 Family recurrent viral infections 276183 Spinocerebellar ataxia type 32 1 Family 370131 White platelet syndrome 1 Family

1 Family 1 Family

1 Family Autosomal dominant myopia-midfacial retrusion440354 sensorineural hearing loss-rhizomelic dysplasia 1 Family syndrome 444099 Autosomal dominant spastic paraplegia type 73 1 Family X-linked colobomatous microphthalmia431140 microcephaly-intellectual disability-short stature 1 Family syndrome

Without specification, published figures are worldwide. An asterisk * indicates European data. BP indicates birth prevalence

Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - March 2016 - Number 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf

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For any questions or comments, please contact us: [email protected] Editor-in-chief :Ana Rath – Editor of the report:Stéphanie Stéphanie Nguengang Wakap – Technical support : Samuel Demarest and Valérie Lanneau The correct form when quoting this document is : «Prevalence of rare diseases: Bibliographic data », Orphanet Report Series, Rare Diseases collection, March 2016, Number 2 : Diseases listed by decreasing prevalence, incidence or number of published cases http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf This Orphanet Report Series is part of the joint action 677024 RD-ACTION which has received funding from the European Union’s Health Programme (2014-2020). The content of this Orphanet Report Series represents the views of the author only and is his/her sole responsibility; it can not be considered to reflect the views of the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.