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Home , Acalvaria, Achalasia microcephaly, Acheiropodia, Agnathia, Aplasia cutis congenita, Arrhinia

Prevalence of rare : Bibliographic data Orphanet May 2008 Rep rt Series

Listed in order of alphabetical

Method

A systematic survey of the literature is being performed in order to provide an estimate of the preva- lence of rare diseases in Europe. An updated report will be published regularly and will replace the previous version. This update contains new epidemiological data and modifications to existing data for which new information has been made available. Search strategy The search strategy is carried out using several data sources: - Websites: Orphanet, e-, GeneClinics, EMEA and OMIM ; - Medline is consulted using the search algorithm: « names» AND Epidemiology[MeSH:NoExp] OR Incidence[Title/abstract] OR Prevalence[Title/abstract] OR Epidemiology[Title/abstract] ; - Medical books, grey literature and reports from experts are also important sources of data. Collected data Prevalence values provided are the mean of the highest and lowest values collected. When prevalence is not documented we calculate it using incidence: - For congenital diseases with birth-onset, prevalence = incidence at birth x (patient life expectancy/general population life expectancy) ; - For the other rare diseases, prevalence = incidence x mean duration ; When no prevalence or incidence data are available, the number of cases reported in the literature is provided. NB: Life expectancy of the French population (78 years) is used as the general population life expectancy. Updated Data New information from available data sources: EMEA, new scientific publications, grey literature, expert opinion. Limitation of the study The exact prevalence rate of each rare disease is difficult to assess from the available data sources. There is a low level of consistency between studies, a poor documentation of methods used, confusion between incidence and prevalence, and/or confusion between incidence at birth and life-long incidence. The validity of the published studies is taken for granted and not assessed. It is likely that there is an overestimation for most diseases as the few published prevalence surveys are usually done in regions of higher prevalence and are usually based on hospital data. Therefore, these estimates are an indication of the assumed prevalence but may not be accurate.

For any questions or comments, please contact us: [email protected] Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Prevalences by alphabetical list of diseases

Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families

2,4-dienoyl-CoA reductase deficiency 1 case Acrofacial Rodriguez type < 10 cases 2,8 dihydroxyadenine urolithiasis 1,7 Acrofacial dysostosis, Nager type 90 cases 3C 25 cases Acrofacial dysostosis, palagonia type 4 cases 3-hydroxy 3-methylglutaryl-CoA (HMG) 6 cases Acrofacial dysostosis, postaxial < 30 cases synthase Acrofacial dysostosis, Preis type 1 case 3-hydroxyacyl-CoA dehydrogenase, long 1 Acro-fronto-facio-nasal dysostosis 5 cases chain, deficiency of Acromegaloid facial appearance < 20 cases 3M syndrome 40 cases syndrome 3-methylcrotonylglycinuria 2,25 Acromegaloid facies - < 20 cases 3-methylglutaconic aciduria, type 1 20 cases 5 3-methylglutaconic aciduria, type 3 10 Acromegaly - cutis verticis gyrata 16 cases 46 xx epibulbar 1 case - corneal leukoma dermoid Acromelanosis < 10 cases 46,XX disorders of sex development 2 cases Acromesomelic dysplasia brahimi bacha 3 cases - skeletal anomalies type 4-hydroxybutyricaciduria 350 cases Acromesomelic dysplasia Hunter- 10 cases 5-oxoprolinase deficiency 8 cases Thompson type 6-pyruvoyl-tetrahydropterin synthase, 248 cases Acromesomelic dysplasia, Maroteaux 50 cases deficiency type 6q terminal 19 cases Acromicric dysplasia < 40 cases Aarskog-Scott syndrome > 200 cases Acroosteolysis dominant type 50 cases Aase-Smith syndrome < 10 cases Acro-pectoral syndrome 22 cases Ablepharon syndrome 15 cases Acro-pectoro-renal field defect 12 cases Abruzzo-Erickson syndrome 4 cases Acropectorovertebral dysplasia < 30 cases Acalvaria < 1** Acrorenal syndrome 20 cases Acanthamoeba keratitis 1 Acro-renal-mandibular syndrome 7 cases Acatalasemia 3,1 Acro-renal-ocular syndrome < 20 families Aceruloplasminemia 0,05 Acute interstitial 3,8 Achalasia - 5 cases Acute lymphoblastic leukaemia 7,5 Achalasia, primary 10 Acute non lymphoblastic leukaemia 7 < 10 families Acute promyelocytic leukaemia 8 > 100 cases Acute Respiratory Distress Syndrome, 30 Adult 4,5 Acyl-CoA dehydrogenase, medium 15 Ackerman syndrome 8 cases chain, deficiency of Acquired generalized lipodystrophy 80 cases Adactylia unilateral 34 , Schinzel type 34 cases Adamantinoma 513 cases Acrocephalosyndactyly 4,6 Adducted - , 3 families Acrocraniofacial dysostosis 2 cases Christian type Acrodermatitis enteropathica, zinc 0,2 Adducted thumbs-arthrogryposis, 5 cases deficiency type Dundar type Acrofacial dysostosis autosomal 2 cases Adenosine monophosphate deaminase 200 cases recessive deficiency Acrofacial dysostosis catania form 6 cases Adenylosuccinate lyase deficiency 50 cases Acrofacial dysostosis postaxial, atypical 1 case Adrenal hyperplasia, congenital 10

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families 1 Amelo-cerebro-hypohidrotic syndrome 19 cases , X-linked 5 Aminopterin embryofetopathy 17 cases Adult Onset Still’s disease 1,23 Amniotic bands 4** ADULT syndrome 14 cases Amoebiasis due to free-living amoebae 1,75 Agammaglobulinemia - microcephaly 3 cases Amyotrophic lateral sclerosis 6 - - severe dermatitis Anaemia, sideroblastic, X-linked 5 families Agammaglobulinemia X-linked 0,45 - Agenesis of the corpus callosum 2 cases insensitivity syndrome 13 - mental retardation - 3,2** - micrognathia 6,5 Aglossia adactylia < 50 cases Angel-shaped phalango-epiphyseal 15 cases situs 30 cases dysplasia inversus 1 Agonadism - - 6 cases diaphragmatic Angioma neurocutaneous, hereditary < 10 families Aicardi syndrome 200 cases , familial 2 families Aicardi-Goutieres syndrome 100 cases Angio-osteohypertrophic syndrome 1000 cases 1,4 1,75 Alar - coloboma 2 cases Aniridia - cerebellar ataxia - mental > 10 families - telecanthus deficiency Albers-Schonberg disease 1 Aniridia absent patella 3 cases ocular - late onset 7 cases Aniridia mental retardation 3 cases sensorineural deafness obesity familial type Albinism-deafness syndrome 1 family Aniridia renal agenesis psychomotor 2 cases retardation Albright hereditary 0,72 Aniridia-mental retardation syndrome 2 cases Albright like syndrome 10 cases Anisakiasis 3,8 300 cases Ankyloblepharon - ectodermal defects 8 families 0,3 - cleft Alopecia - congenita 1 family Ankyloblepharon filiforme - imperforate 2 families palmoplantaris anus Alopecia - contractures - 5 cases Ankylosing vertebral hyperostosis with 8 cases - mental retardation tylosis Alopecia - hypogonadism - 2 cases - onychodystrophy with 11 cases extrapyramidal disorder hypoplasia or absence of distal Alopecia- - pyorrhea - mental 12 cases phalanges subnormality Anonychia microcephaly 5 cases 10,5 Anonychia with flexural pigmentation 3 cases Alpers syndrome 0,025 Anophthalmia - hypothalamo-pituitary 30 cases Alpha thalassemia- mental retardation, 168 cases insufficiency X-linked Anophthalmia - megalocornea - 3 cases Alpha-1 antitrypsin deficiency 25 cardiopathy - skeletal anomalies Alpha-mannosidosis 0,1 Anophthalmia - , 14 Alpha-sarcoglycanopathy 0,57 isolated 2 Anophthalmia - - obesity 1 case Alström syndrome 300 cases Anophthalmia plus syndrome 4 cases Alveolar echinococcosis < 1000 cases Anophthalmia/microphthalmia - 14 cases Alzheimer disease, familial 5,3 Amaurosis - hypertrichosis 2 cases Anorchidia, bilateral 50 cases Amaurosis congenita of Leber 10 Anorectal malformation 24 Ambras syndrome 10 cases Antisynthetase syndrome 1,5 , autosomal recessive 3 cases Antley-Bixler syndrome 34 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Antley-Bixler-like syndrome - 16 cases Ataxia - deafness - optic , lethal 12 cases ambiguous genitalia - disordered Ataxia telangiectasia 1 steroidogenesis Ataxia, autosomal recessive, Beauce 57 cases Aortic syndrome, Loeys-Dietz 10 families type type Ataxia-deafness-retardation syndrome 8 cases Aortic arch anomaly peculiar facies 4 cases mental retardation Atelosteogenesis I 12 cases Aortic arch interruption 0,3** Atelosteogenesis II 25 cases Aortic dilatation- joint hypermobility- 22 cases Atelosteogenesis III 12 cases arterial tortuosity Athabaskan brainstem dysgenesis 10 cases Aorto-ventricular tunnel 130 cases syndrome 1,25 - deafness - 2 cases - epilepsy - nephropathy Aphalangia - - microcephaly 1 family Atkin-Flaitz syndrome 14 cases Aphalangy - hemivertebrae - 3 cases urogenital-intestinal dysgenesis Atransferrinemia 9 cases Aplasia cutis - myopia 4 cases Atresia of small intestine 20 - intestinal 3 cases atrioventricular 11 cases lymphangiectasia conduction Aplasia cutis congenita of limbs 6 cases Atrial tachyarrhythmia with short pr 12 cases recessive interval Aplastic anaemia 0,4 Atrioventricular canal, complete 15** - mental retardation 3 cases Atrioventricular canal, partial 20 - dysmorphism Atypical coarctation of 0,17** Arachnodactyly abnormal 5 cases Aughton syndrome 2 cases mental retardation Auricular abnormalities - cleft lip 2 cases AREDYLD syndrome 3 cases with or without cleft palate - ocular 31 cases abnormalities Arhinia microphthalmia 4 cases Auriculoocular anomalies - cleft lip 2 cases 13 cases Auriculoosteodysplasia 2 families 20 cases Aurocephalosyndactyly 5 cases Arrhythmogenic right ventricular 43,5 45 dysplasia Autoimmune lymphoproliferative 100 cases Arterial dissection - 4 cases syndrome Arterial tortuosity < 40 cases Autoimmune polyendocrinopathy, type 4 1 , enthesitis-related 5,7 Axenfeld-Rieger anomaly - 3 cases Arthritis, juvenile psoriatic 4,2 hydrocephaly - skeletal abnormalities Arthritis, oligoarticular juvenile 20,5 Babesiosis 40 cases Arthritis, systemic-onset, juvenile 6,3 Bacterial toxic-shock syndrome 3 idiopathic Bamforth syndrome 5 cases Arthrogryposis - , lethal 2 cases form Bangstad syndrome 2 cases Arthrogryposis - renal dysfunction < 150 cases Banki syndrome 1 family - cholestasis Barber-Say syndrome 10 cases Arthrogryposis multiplex congenita 30 Bardet-Biedl syndrome 0,8 Arthrogryposis multiplex congenita 10 cases Bartsocas-Papas syndrome 24 cases -whistling 0,12 Arthrogryposis-like anomaly 1 family - sensorineural deafness B-cell chronic lymphocytic leukaemia 32 Ascher syndrome 50 cases Beckwith-Wiedemann syndrome 7,3 Beemer-Ertbruggen syndrome 2 cases Astley-Kendall dysplasia < 10 cases Behcet disease 2,5 Ataxia - apraxia - mental retardation, 9 cases X-linked Bencze syndrome 2 families

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Benign syndrome 4 cases malformation - congenital 2 cases disease - postaxial Benign paroxysmal torticollis of infancy 50 cases Branchial arch syndrome, X-linked 7 cases Bernard-Soulier syndrome 100 cases Branchiogenic deafness syndrome 5 cases Best disease 4,4 Branchio-oculo-facial syndrome < 50 cases Beta-mannosidosis 14 cases Branchio-skeleto-genital syndrome 3 cases Beta-sarcoglycanopathy 0,57 Breast cancer, familial 25 Beta-ureidopropionase deficiency 5 cases Bronchopneumopathy, chronic, due to < 20 cases Bethlem myopathy 100 cases TAP deficiency Bickel-Fanconi glycogenosis 112 cases Bronchopulmonary dysplasia 13 Biliary atresia 5,6 Brown-Vialetto-van Laere syndrome < 100 cases Biliary tract malformation - renal 6 cases Budd-Chiari syndrome 1,5 failure Buerger’s disease 12,5 Birt-Hogg-Dube syndrome > 60 families Bullous dystrophy, macular type 2 families Björnstad syndrome 33 cases Bullous ichthyosiform erythroderma 0,4 Blackfan-Diamond disease 0,32 congenita Blaichman syndrome 1 case 2,5 Blepharo-cheilo-dontic syndrome < 50 cases Bullous systemic lupus erythematosus 70 cases Blepharo-facio-skeletal syndrome 2 cases Buttiens- 3 cases Blepharonasofacial malformation 2 families CADASIL 500 cases syndrome Calpainopathy 3,8 Blepharophimosis - ptosis - esotropia 6 cases - syndactyly - short stature Calvarial doughnut lesions - 20 cases fragility Blepharoptosis - myopia - ectopia 3 cases lentis CAMFAK syndrome 3 families > 100 cases CAMOS syndrome 5 cases Blue rubber bleb > 200 cases Campomelia Cumming type 8 cases Bone dysplasia azouz type 1 case 0,35 Bone dysplasia corpus callosum 1 case Camptobrachydactyly 1 family agenesis - fibrous tissue 3 cases Bone dysplasia lethal holmgren type 4 cases hyperplasia - skeletal dysplasia Bone fragility, craniosynostosis, 4 cases Camptodactyly - tall stature - 30 cases proptosis, - Bone tumor 10 Camptodactyly - taurinuria 4 families Bonnemann-Meinecke-Reich syndrome 4 cases Camptodactyly syndrome guadalajara 8 cases type 1 Book syndrome 25 cases Camptodactyly syndrome, Guadalajara 2 cases 10 cases type 2 BOR syndrome 2,5 Camurati engelmann disease 200 cases Bosley-Salih-Alorainy syndrome 9 cases Cantrell pentalogy 0,55** Botulism 0,05 57 cases Boutonneuse fever 17 Carbamoylphosphate synthetase 0,7 Bouwes Bavinck syndrome 2 cases deficiency Bowen-Conradi syndrome 44 cases Carcinoma of the gallbladder 6,5 - arterial > 10 families Cardiac conduction disease, dilated 10 cases Brachydactyly long type 4 cases and brachydactyly Brachymorphism - onychodysplasia 9 cases Cardiogenital syndrome 7 cases - dysphalangism Cardiomyopathy - - spine 9 cases Brachytelephalangy - dysmorphism 2 cases disease - Cardiomyopathy - renal anomalies 2 cases Braddock syndrome 2 cases Cardiomyopathy, familial dilated 17,5 Bradyopsia 5 cases Carey fineman ziter syndrome < 20 cases ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families 160 cases CEDNIK syndrome 7 cases Carnitine palmitoyl transferase 1 35 cases Celiac disease epilepsy occipital 170 cases deficiency calcifications Carnitine palmitoyl transferase 2 > 100 cases Central neurocytoma > 100 cases deficiency Cerebellar ataxia - areflexia - 2 families Carnitine-acylcarnitine translocase 30 cases - optic atrophy - sensorineural hearing deficiency loss Carnosinemia 30 cases Cerebellar ataxia, autosomal dominant 2,15 Caroli’s disease < 250 cases Cerebellar ataxia, autosomal recessive 7 40 cases Cerebellar ataxia, autosomal recessive 3 families - blindness - deafness Carpo tarsal < 10 cases Cerebellar ataxia, autosomal recessive 1 family Carpo tarsal osteolysis recessive < 10 cases - saccadic intrusion Castleman disease 400 cases Cerebral arteriovenous fistula 6 Cataract - hypertrichosis - intellectual 1 case Cerebral gigantism - cysts < 10 cases deficit Cerebro-costo-mandibular syndrome 60 cases Cataract - microphthalmia - septal 2 cases defect Cerebro-oculo-nasal syndrome 10 cases Cataract - nephropathy - 2 cases Cerebroretinal vasculopathy 3 families encephalopathy Ceroid lipofuscinosis, neuronal 4 Cataract- ataxia - deafness 2 cases Cervical hypertrichosis - peripheral 3 cases Cataract cardiomyopathy 30 cases neuropathy Cataract deafness hypogonadism 3 cases CHAND syndrome > 10 cases Cataract mental retardation 10 cases Chaotic atrial 100 cases hypogonadism Char syndrome 10 cases Cataract-glaucoma 3 families Charcot-Marie-Tooth disease 32,5 Cataract-microcornea syndrome 8 families Charcot-Marie-Tooth disease - 10 cases Catel-Manzke syndrome 27 cases nephropathy Cat-eye syndrome 1,35 Charcot-Marie-Tooth disease, X-linked 1,6 Cat-scratch disease 6,6 CHARGE association 0,14 Caudal dysgenesis familial type 4 cases Chediak-Higashi syndrome > 10 cases CDG syndrome 1,5** CHILD syndrome 30 cases CDG syndrome type Ia 300 cases Choanal atresia - deafness - cardiac 5 cases defects - dysmorphism CDG syndrome type Ib 20 cases 10 CDG syndrome type Ic > 30 cases - lymphoedema 50 cases CDG syndrome type Id 5 cases Cholestasis pigmentary retinopathy 4 cases CDG syndrome type Ie 7 cases cleft palate CDG syndrome type If 4 cases Cholesteryl ester storage disease < 50 cases CDG syndrome type Ig 6 cases Chondrodysplasia - disorder of sex 2 cases CDG syndrome type Ih 5 cases development CDG syndrome type Ii 1 case Chondrodysplasia lethal recessive 4 cases CDG syndrome type IIa 4 cases Chondrodysplasia punctata, rhizomelic 1 CDG syndrome type IIb 1 case type Chondrodysplasia situs inversus 1 case CDG syndrome type IId 1 case polydactyly CDG syndrome type IIe 2 cases Chondrodysplasia, Blomstrand type 13 cases CDG syndrome type Ij 1 case Chordoma 0,05 Chorioretinal atrophy, progressive 2 families CDG syndrome type Ik 4 cases bifocal CDG syndrome type IL 2 cases Choroidal atrophy alopecia 2 cases CDG syndrome, type IIh 2 cases Choroidal dystrophy, central areolar 3,33

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families 2 Congenital - facial 100 cases dysmorphism - neuropathy Choroideremia deafness obesity 4 cases Congenital microcephalus 2 cases Choroido cerebral calcification 10 cases quadriplegia syndrome infantile form Congenital indifference to pain 20 cases Christ-Siemens-Touraine syndrome 0,35 Congenital lobar emphysema 4,5 Y deletion 42 Congenital rubella syndrome 1** Chronic hiccup 1 Contractures cleft 2 cases Chronic inflammatory demyelinating 4,4 lip palate polyneuropathy Cooper-Jabs syndrome 2 cases Chronic recurrent multifocal > 260 cases , juvenile Corneal anesthesia deafness mental 2 cases retardation Churg-Strauss syndrome 1 - perceptive deafness < 10 cases Chylomicron retention disease 40 cases Corneal dystrophy ichthyosis 1 case CINCA syndrome 100 cases microcephaly mental retardation Cleft lip and palate malrotation 4 cases Corneal-cerebellar syndrome 2 cases cardiopathy Cornelia de Lange syndrome 5,25 Cleft lip palate - mental retardation 2 cases - corneal opacities Coronary disease - 1 family Cleft lip retinopathy 2 cases - hypertension - diabetes - Cleft palate - cardiac defect - genital 5 cases anomalies - Corpus callosum agenesis neuronopathy 19 Cleft palate lateral synechia syndrome 7 cases Corpus callosum dysgenesis, X-linked 11 cases recessive Cleft palate short stature vertebral 2 cases anomalies Corpus callosum, agenesis - cataract 8 cases - immunodeficiency Cleft palate stapes fixation oligodontia 2 cases Cortical blindness - mental retardation 3 cases Cleido rhizomelic syndrome 2 cases - polydactyly Clouston syndrome 1 Corticobasal degeneration 4 Cloverleaf syndrome 150 cases -sensitive aseptic 49 cases COACH syndrome 8 cases abscesses Coats disease 2 200 cases Cobb syndrome 35 cases Costocoracoid ligament congenitally 1 family 200 cases short Coffin-Lowry syndrome 0,55 0,45 Coffin-Siris syndrome 40 cases Coxoauricular syndrome 4 cases Cogan syndrome 200 cases Coxo-podo-patellar syndrome 47 cases Cohen syndrome 100 cases Cranio fronto nasal dysplasia poland 3 cases Collagenous 10,5 anomaly Coloboma of macula - brachydactyly 12 cases Cranio osteoarthropathy 4 cases type B Craniodiaphyseal dysplasia > 20 cases Coloboma uveal with cleft lip palate 12 cases Craniodigital syndrome - intellectual 5 cases and mental retardation deficit Coloboma, ocular 1 Craniofacial conodysplasia 1 family Colobomatous microphthalmia heart 10 cases Craniofacial dysmorphism - coloboma 3 cases disease hearing loss - corpus callosum agenesis Cone rod dystrophy 2,5 Craniofacial dyssynostosis 0,05 Cone rod dystrophy amelogenesis 29 cases Craniofacial-deafness-hand syndrome 3 cases imperfecta Craniofaciocardioskeletal syndrome 4 cases Congenital , isolated < 15 cases Craniofrontonasal dysplasia, Teebi type 20 cases Congenital brain dysgenesis due to < 30 cases glutamine synthetase deficiency Craniolenticulosutural dysplasia 21 cases Congenital bronchobiliary fistula 23 cases Craniometaphyseal dysplasia 70 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Craniosynostosis - dysmorphism - 5 cases Deaf blind 2 cases brachydactyly Deafness - genital anomalies - 2 cases Craniosynostosis - intracranial 3 cases metacarpal and metatarsal calcifications Deafness - lymphoedema - leukaemia < 10 cases Craniosynostosis dandy walker 4 cases Deafness - opticoacoustic nerve 3 cases hydrocephalus atrophy - dementia Craniosynostosis fibular aplasia 2 cases Deafness - 4 cases Craniosynostosis radial aplasia type 2 cases - arterial disease imaizumi Deafness - - achalasia 2 cases Craniosynostosis, Boston type 19 cases Deafness skeletal dysplasia lip 8 cases Craniosynostosis, Philadelphia type 1 family granuloma Craniotubular syndrome 2 cases Deafness, , 6 cases defects Creutzfeldt-Jakob disease 0,1 Deafness-infertility syndrome 3 families Crigler-Najjar syndrome 1 Deafness-mental retardation, Martin- 3 cases Crisponi syndrome 18 cases Probst type Criss-cross heart 0,8 Deafness-mental retardation, Martin- 3 cases Crouzon disease 2 Probst type 1,33* Deafness-tubular acidosis-anaemia 2 cases Cryptomicrotia - brachydactyly - excess 2 cases Defective expression of HLA class 2 100 cases fingertip arch Dehydratase deficiency 21 cases 34 Deletion 2q24 23 cases Curry-Jones syndrome 5 cases Delta-sarcoglycanopathy 0,57 Cutaneous albinism, ermine phenotype 3 cases DEND syndrome 14 cases Cutaneous 50 Dentatorubral pallidoluysian atrophy < 0,3 Cutaneous lymphomas 8,3 Dentinogenesis imperfecta - short 2 cases Cutaneous 0,75 stature - hearing loss - mental Cutaneous neuroendocrine carcinoma 0,5 retardation Cutaneous photosensitivity colitis 3 cases Denys-Drash syndrome 150 cases lethal of the iris, acute, 5 cases Cutis gyrata 6 cases bilateral craniosynostosis Dermatitis herpetiformis 20,2 > 100 cases Dermato-cardio-skeletal syndrome 2 cases Cutis marmorata telangiectatica 300 cases Borrone type congenita Dermatofibrosarcoma protuberans 10 Cutis verticis gyrata - mental deficit 1,02 Dermatoleukodystrophy 2 cases Cyprus facial neuromusculoskeletal 1 family Dermatomyositis 14,8 syndrome Dermatoosteolysis Kirghizian type 5 cases Cystathioninuria 7 Dermo-odonto dysplasia 14 cases 12 Dermopathy restrictive lethal 30 cases Cystic hamartoma of and < 5 cases Desbuquois syndrome > 40 cases lethal - cleft palate 2 cases 2 cases Cystinosis 0,5 Developmental delay due to 2- < 30 cases methylbutyryl-CoA dehydrogenase 14 deficiency Cystoid macular dystrophy 6 families Developmental dysphasia familial 6 families Dacryocystitis 5 cases Developmental malformations - 2 cases Dahlberg-Borer-Newcomer syndrome 2 cases deafness - dystonia Dandy walker 2 cases , nephrogenic 0,5 Dandy walker malformation postaxial 2 cases Diabetes mellitus, neonatal 0,2 polydactyly Diabetes mellitus, permanent neonatal 4 cases Darier disease 1,5 - pancreatic and cerebellar agenesis

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Diabetes, neonatal - congenital 2 cases Earlobes, thickened - conductive 2 families - congenital glaucoma deafness - hepatic fibrosis - polycystic kidneys Early infantile epileptic encephalopathy 88 cases Diaphanospondylodysostosis < 10 cases Early myoclonic encephalopathy 30 cases Diaphragmatic defect - limb deficiency 4 cases Early onset torsion dystonia 0,4 - skull defect Ear-patella-short stature syndrome 42 cases - exomphalos 13 cases - corpus callosum agenesis Ebstein anomaly 0,75 Diaphragmatic hernia, congenital 15 Ectodermal dysplasia - absent < 30 cases dermatoglyphs Diastrophic dwarfism 3,5 Ectodermal dysplasia - anhidrotic, 2 cases Diffuse leiomyomatosis - Alport 0,1 with immunodeficiency - syndrome X-linked - lymphoedema Diffuse neonatal haemangiomatosis < 70 cases Ectodermal dysplasia - blindness 2 cases Diffuse palmoplantar 10 cases Ectodermal dysplasia - skin fragility 10 cases - syndrome Diffuse , 2,5 Ectodermal dysplasia alopecia preaxial 1 case Norrbotten dominant type polydactyly Digitorenocerebral syndrome < 10 cases Ectodermal dysplasia arthrogryposis 1 case Digitotalar dysmorphism 6 diabetes mellitus Dihydropteridine reductase deficiency 134 cases Ectodermal dysplasia berlin type 4 cases Dihydropyrimidinuria 7 cases Ectodermal dysplasia mental retardation 1 case syndactyly Dincsoy-Salih-Patel syndrome 2 cases Ectodermal dysplasia, hypohidrotic 3 cases Disorder of sex development - mental 3 cases - hypothyroidism - ciliary dyskinesia retardation Ectodermal dysplasia, hypohidrotic, 40 cases Distal 5q 10 cases autosomal dominant Distal monosomy 8p 20 cases ‘Ectodermal dysplasia, ‘’pure’’ -nail < 20 cases Distal myopathy with posterior leg and 12 cases type’ anterior upper limb involvement Ectodermic dysplasia hypothyroidism 3 cases Distal myopathy with vocal cord 12 cases cleft weakness chorioretinal dystrophy 4 cases Distal myopathy, Nonaka type 0,1 myopia Distal myopathy, Welander type 10 Ectopia lentis isolated 6,4 Distal myopathy, with early respiratory 24 cases Ectrodactyly - ectodermal dysplasia 5 cases muscle involvement without clefting DOOR syndrome < 50 cases EEM syndrome 7 families Dopamine beta-hydroxylase deficiency 12 cases Ehlers-Danlos syndrome type 10 1 family Dopa-responsive dystonia 0,3 Ehlers-Danlos syndrome type 3 12,5 Double outlet left ventricle 32 cases Ehlers-Danlos syndrome type 4 1 Double -hemivagina-renal < 60 cases Ehlers-Danlos syndrome type 7C 7 cases agenesis Ehlers-Danlos syndrome, classic type 3,5 Duane anomaly - myopathy - scoliosis 2 cases Ehlers-Danlos syndrome, type 5 2 families Duane syndrome 10 Ehrlichiosis < 50 cases Dubowitz syndrome 150 cases Eiken syndrome 6 cases Duker-Weiss-Siber syndrome 4 cases 30 cases 8,55 Elliptocytosis, hereditary 35 Dyggve-Melchior-Clausen disease 60 cases Ellis Van Creveld syndrome 150 cases Dyschondrosteosis - nephritis 1 family Emery-Dreifuss muscular dystrophy 0,3 Dyserythropoietic anaemia, congenital 1 0,1 Encephalo cranio cutaneous lipomatosis 45 cases Dysmorphism - short stature - deafness 2 cases Encephalopathy due to < 30 cases - pseudohermaphroditism hydroxykynureninuria

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf  Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Encephalopathy due to sulphite oxidase 50 cases Factor XIII deficiency, congenital 0,04 deficiency Fahr syndrome < 20 families Encephalopathy with neuroserpin > 5 families Familial adenomatous polyposis 5,25 inclusion bodies, familial form Familial 0,1 600 cases Familial 550 cases Endocrine tumour 1 Familial hematuria, autosomal 8 cases Eng strom syndrome 2 cases dominant - retinal arteriolar tortuosity Eosinophilic fasciitis 200 cases - contractures Eosinophilic 280 cases Familial syndrome with < 20 families predisposition to acute myelogenous , acute > 100 cases leukaemia idiopathic Familial platelet syndrome with 13 families Epidermal nevus syndrome > 400 cases predisposition to acute myelogenous simplex - limb < 20 cases leukaemia girdle muscular dystrophy Fanconi anaemia 1 Epidermolysis bullosa, acquired 100 cases Fanconi ichthyosis dysmorphism 6 cases Epidermolysis bullosa, dystrophic 0,27 -- complex 1,5 Epidermolysis bullosa, epidermolytic 2,5 Fetal syndrome 40 Epidermolysis bullosa, junctional 0,06 Fetal methyl mercury syndrome 800 cases Epilepsy microcephaly skeletal 2 cases Fetal varicella syndrome > 100 cases dysplasia Fibrinogen deficiency, congenital 0,15 Epilepsy telangiectasia 6 cases 11 cases Epilepsy, pyridoxin-dependent 0,15 Fibrodysplasia ossificans progressiva 0,08 Epiphyseal dysplasia multiple 5 Fibromatosis, gingival - progressive 2 families , type 3 1 family deafness Episodic ataxia, type 4 2 families Fibrous dysplasia of bone < 0,05 Erdheim-Chester disease 178 cases Fibular aplasia - ectrodactyly < 50 cases Erythermalgia, primary 30 families Fibular dimelia - 11 cases Erythroderma lethal congenital 17 cases Fine-Lubinsky syndrome 5 cases ataxia 25 cases Fingerprints absence - congenital milia 14 cases Erythrokeratodermia variabilis, Mendes > 200 cases Flynn aird syndrome 10 cases da Costa type 300 cases Esophageal atresia 25 Focal dystonia 11,7 Esophageal carcinoma 8 Focal facial dermal dysplasia < 10 families Esthesioneuroblastoma < 1000 cases Focal myositis 50 cases Evans syndrome 0,1 Folate malabsorption, hereditary 17 cases Ewing sarcoma 0,1 Follicular 36 Exostoses, multiple 2 Foveal hypoplasia presenile cataract 11 cases Eyebrow duplication syndactyly 3 cases 14,25 1,75 150 cases Facial dysmorphism macrocephaly 3 cases myopia dandy walker Freeman-Sheldon syndrome 100 cases Facial onset sensory and motor 4 cases Fried syndrome 1 family neuronopathy Friedreich ataxia 2,5 Faciocardiomelic dysplasia lethal 3 cases Frontometaphyseal dysplasia < 30 cases Facioscapulohumeral muscular 7 Frontotemporal dementia 3 dystrophy Fronto-temporal dementia and 50 cases Factor II deficiency 10 Parkinsonism linked to Factor V deficiency 0,1 (FTDP-17) Factor VII deficiency 0,25 Fructose intolerance 5 Factor XI deficiency, congenital 0,1 Fructose-1,6-bisphosphatase deficiency 2,5

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 10 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Fryns syndrome 7** Glycogen storage, type 0 16 cases Fucosidosis 100 cases Goldberg-Shprintzen megacolon 10 cases syndrome Fuhrmann syndrome 11 cases 3,5 Fumaric aciduria > 20 cases Goldmann-Favre syndrome < 50 cases Fuqua-Berkovitz syndrome 2 cases Gombo syndrome 4 cases 6,6 Gonadal dysgenesis, XX type 12 Galloway-Mowat syndrome 40 cases Gonadal dysgenesis, XY type - 2 cases Gamma aminobutyric acid transaminase 2 cases associated anomalies deficiency Goodman syndrome 3 cases Gamma-glutamyl transpeptidase 7 cases deficiency Goodpasture syndrome 0,64 Gamma-glutamylcysteine synthetase 9 cases Gorham-Stout disease 200 cases deficiency Gorlin syndrome 1 Gamma-sarcoglycanopathy 1,96 Gorlin-Chaudhry-Moss, syndrome 4 cases GAPO syndrome 27 cases GRACILE syndrome 2,12** Gardner-Morrison-Abbott syndrome 3 cases Graft versus host disease 3,4 Gastric cancer 20 Grange syndrome 6 cases Gastrointestinal stromal tumor 13 Granulomatous arthritis of childhood 40 families 12 Granulomatous disease, chronic 0,2 Gaucher disease 2 Granulomatous slack skin < 50 cases Gaucher disease - ophthalmoplegia < 10 cases Gräsbeck-Imerslund disease 300 cases - cardiovascular calcification Gray platelet syndrome 20 cases Gaucher disease type 1 0,94 Greenberg dysplasia < 10 cases Gaucher disease type 2 0,01 Greig syndrome 100 cases Gaucher disease type 3 0,05 Griscelli disease 60 cases Geleophysic dwarfism 27 cases Growth deficiency - brachydactyly 2 families Gelineau disease 49 - dysmorphism Genitopatellar syndrome 7 cases Growth delay - intellectual deficit 4 cases German syndrome 5 cases - mandibulofacial dysostosis - microcephaly - cleft palate Geroderma osteodysplastica 30 cases Growth delay due to insulin-like growth 4 cases Giant cell 8,9 factor I deficiency Giant pigmented hairy nevus 2 Growth retardation - microcephaly - 4 cases Glaucoma - ectopia - microspherophakia 3 cases digital abnormalities - - stiff joints - short stature GTP cyclohydrolase I deficiency 17 cases Glaucoma - sleep apnoea 5 cases Guanidinoacetate methyltransferase 9 cases Glioblastoma 11 deficiency Global developmental delay - 3 cases Guillain-Barré syndrome 3,45 osteopenia - ectodermal defect Haemolytic anaemia due to adenylate 12 cases Glomerulonephritis sparse hair < 10 cases kinase deficiency telangiectases Haemolytic anaemia due to glutathione 3 cases Glucocorticoid deficiency, familial 50 cases reductase deficiency Glucose-galactose malabsorption 200 cases Haemolytic anaemia, nonspherocytic, 17 families Glucosephosphate isomerase deficiency 50 cases due to hexokinase deficiency Glutaryl-CoA dehydrogenase deficiency 0,4 Hair defect photosensitivity mental 3 cases retardation Glutathione synthetase deficiency 65 cases Hallermann-Streiff-Francois syndrome < 100 cases Glycogen storage disease due to LAMP- 84 cases 2 deficiency Harding ataxia 1 type 2 1,1 Hartnup syndrome 4 Glycogen storage disease type 4 0,6 Heart defects - limb shortening 2 cases Glycogen storage disease type 7 < 30 cases Hec syndrome 2 cases ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 11 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Helicoid peripapillary chorioretinal 100 cases Hydrocephalus - costovertebral 8 cases degeneration dysplasia - Sprengel anomaly 4,15 Hydrocephaly tall stature joint laxity 2 cases Hemiplegic , familial 6,5 Hydrolethalus 5** Hemolytic anaemia, lethal - genital 2 cases Hypercoagulability syndrome, due to 2 cases anomalies glycosylphosphatidylinositol deficiency Hemophilia 7,7 Hyperferritinemia, hereditary, with > 64 cases congenital cataracts Hemophilia, acquired 0,1 Hyperglycinemia, isolated nonketotic 0,2 Hemorrhagic disorders due to collagen < 20 cases receptors deficiency Hyperimmunoglobinemia D with 180 cases recurrent fever Hennekam syndrome > 50 cases Hyperkalemic periodic paralysis 0,75 Hennekam-Beemer syndrome 2 cases Hyperkeratosis - 10 cases Hepatic venoocclusive disease 11 syndrome Hepatic veno-occlusive disease - < 25 cases immunodeficiency Hyperlipidemia type 3 7,8 , chronic autoimmune 0,75 Hyperlipoproteinemia type 1 0,6 Hereditary inclusion body myopathy 19 cases 0,2 - joint contractures - ophthalmoplegia Hypertrichosis cubiti - short stature 28 cases Hereditary sensory and autonomic 35 cases Hypertrichosis lanuginosa congenita < 100 cases neuropathy, type 2 Hypertrichosis lanuginosa, acquired 60 cases Hereditary vascular retinopathy 1 family Hereditary vascular retinopathy 1 family Hypertrichosis, anterior cervical, < 20 cases isolated Hermansky-Pudlak syndrome 0,15 Hypertrichotic 18 cases HERNS syndrome 3 families 3,3 Hersh-Podruch-Weisskopf syndrome 2 cases Hypocomplementaemic leucocytoclasic < 100 cases Heterotaxia 2,5 vasculitis Hidrotic ectodermal dysplasia Halal 4 cases due to CD19 4 cases type deficiency Hidrotic ectodermal dysplasia type 6 cases Hypogonadism - 3 cases Christianson-Fourie Hypokalemic periodic paralysis 1 Hirschsprung disease 20 Hypokeratosis, palmo-plantar, 17 cases Hirschsprung disease - deafness 2 cases circumscribed - polydactyly Hypomagnesemia with hypocalciuria 3 families Hirschsprung disease - nail hypoplasia 3 cases - dysmorphism Hypomagnesemia with normocalciuria 2 cases 4 Hypomandibular faciocranial dysostosis 4 cases , classical 10,5 Hypomyelination - 8 cases Holoprosencephaly 7 Hypomyelination - hypogonadotropic 4 cases hypogonadism - Holt-Oram syndrome 1 Hypomyelination - hypogonadotropic 4 cases Homocarnosinosis 4 cases hypogonadism - hypodontia due to cystathionine 0,4 Hypoparathyroidism familial isolated < 10 families beta-synthase deficiency Hypoparathyroidism X-linked 2 families Humeroradial synostosis 150 cases Hypoparathyroidism, deafness and renal 12 cases Humeroradioulnar synostosis 30 cases disease (HDR) Humerospinal dysostosis 5 cases - microphthalmia < 10 cases Humeroulnar synostosis 5 cases Hypopituitarism - postaxial polydactyly 6 cases Huntington disease 6,2 Hypotelorism - cleft palate - 13 cases Hyaluronidase deficiency 1 case hypospadias Hydrocephalus - blue sclerae - 1 family Hypothyroidism - - cleft 1 case nephropathy palate

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 12 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Hypothyroidism - dysmorphism 5 cases Internal carotid agenesis 100 cases - postaxial polydactyly - intellectual Interstitial granulomatous dermatitis < 20 cases deficit with arthritis Hypothyroidism, congenital 29 Iris coloboma with ptosis - intellectual 10 cases Hypotrichosis - lymphoedema - 4 cases deficit telangiectasia Iris dysplasia - - deafness 2 cases Hypotrichosis simplex 38 cases -like syndrome 6 cases Hypotrichosis-mental retardation lopes 2 cases 1 type IVIC syndrome 4 families IBIDS syndrome 15 cases Jackson-Weiss syndrome 2 families ICF syndrome 50 cases 150 cases Ichthyosis - hepatosplenomegaly 2 cases - cerebellar degeneration Jeune syndrome 0,2 Ichthyosis - male hypogonadism 5 cases Job syndrome 250 cases Ichthyosis - oral and digital anomalies 2 cases Johanson-Blizzard syndrome 23 cases Ichthyosis alopecia eclabion ectropion 4 cases Johnson neuroectodermal syndrome < 30 cases mental retardation Joubert syndrome 0,85 Ichthyosis bullosa of Siemens < 20 cases Juberg hayward syndrome 10 cases Ichthyosis congenita biliary atresia 2 cases Juvenile hyaline fibromatosis 50 cases Ichthyosis congenita, harlequin type < 100 cases Juvenile macular degeneration, 7 families Ichthyosis follicularis - atrichia - 10 cases hypotrichosis photophobia Juvenile temporal arteritis 20 cases Ichthyosis prematurity syndrome 16 families 1,16 Ichthyosis, X-linked 16,6 Kaler garrity stern syndrome 2 cases Idiopathic hypereosinophilic syndrome 10 Kallmann syndrome 7,7 Idiopathic 4 Kallmann syndrome - heart disease 8 cases IMAGe syndrome < 20 cases Kaposi’s sarcoma 1,7 Iminoglycinuria 6,68 Kapur-Toriello syndrome 2 cases Immune dysregulation - 7 families Kasabach-Merritt syndrome > 175 cases polyendocrinopathy - enteropathy, X linked KBG syndrome 45 cases Immunodeficiency due to interleukin-1 < 15 cases Kearns-Sayre syndrome 2 receptor-associated kinase-4 deficiency Kennedy disease 2,8 Immunodeficiency due to selective 100 cases Keratoderma hypotrichosis leukonychia 2 cases anti-polysaccharide antibody deficiency Keratoderma palmoplantar - deafness < 10 families Immunodeficiency with natural-killer 4 cases cell deficiency Keratoderma palmoplantar - spastic 25 cases paralysis Immunodeficiency, common variable 7,5 Keratosis follicularis - dwarfism - 6 cases Inappropriate antidiuretic hormone 2 cases cerebral atrophy secretion syndrome Keratosis palmaris et plantaris - < 20 cases Inclusion body myositis, IBM 0,49 0,2 Keratosis palmoplantaris - esophageal < 10 families Infant epilepsy with migrant focal 29 cases carcinoma crisis Ketoacidosis due to betaketothiolase 60 cases Infantile neuroaxonal dystrophy > 150 cases deficiency Inflammatory pseudotumor of the liver 143 cases KID syndrome > 100 cases Insomnia, familial fatal 27 cases Kimura disease 200 cases Insulin resistance, short fifth 1 family Klippel-Feil syndrome 2 metacarpals Kniest-like dysplasia, lethal 2 cases Intellectual deficit, severe - epilepsy 2 cases Krabbe disease 0,75** - anal anomalies - distal phalangeal hypoplasia Kudo tamura fuse syndrome 2 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 13 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Lacrimo-auriculo-dento-digital 20 cases Lipodystrophy, partial acquired 250 cases syndrome Lipoid proteinosis > 280 cases Lafora disease < 0,1 Lissencephaly - immunodeficiency 1 case Lambert-Eaton myasthenic syndrome 1 type 2 0,12 > 0,33 Lissencephaly type III - familial foetal 5 cases Langerhans cell histiocytosis 2 akinesia sequence 100 cases Lissencephaly type III - metacarpal 2 cases bone dysplasia Laryngeal abductor paralysis - mental < 20 cases retardation Liver disease - retinitis pigmentosa 4 cases - polyneuropathy - epilepsy Laryngo-tracheo-esophageal cleft 1,5 Long QT syndrome, familial 25 Lateral body wall complex 2** Lopez-Hernandez syndrome 11 cases < 5 cases Low birth weight - dwarfism - 2 cases LCAT deficiency 30 families dysgammaglobulinemia Leber hereditary optic neuropathy 6,5 Lowe syndrome 0,19 Legg-Calve-Perthes disease 23 Lumbosacral vertebrae, posterior fusion 3 cases Leigh syndrome 2,75** of - blepharoptosis Lennox-Gastaut syndrome 15 Lung cancer, small cell 10 Lenz-Majewski hyperostotic dwarfism 7 cases Lymphangioleiomyomatosis 0,1 LEOPARD syndrome > 70 cases Lymphoedema - atrial septal defects 3 cases Leprechaunism 0,1** - facial changes Leptospirosis 0,24 Lymphoedema - cerebral arteriovenous 5 cases anomaly Lesch-Nyhan syndrome 0,38 Lymphoedema, congenital 8,8 Lethal osteosclerotic bone dysplasia 8 families Macrocephaly - Cutis Marmorata 40 cases Leucinosis 15,6 Telangiectatica Congenita Leukaemia, chronic myeloid 6 Macrocephaly - immune deficiency 2 cases Leukocyte adhesion deficiency (LAD) < 350 cases - anemia Leukodystrophy with oligodontia 4 cases Macrocephaly - short stature - 2 cases paraplegia Leukoencephalopathy - metaphyseal 4 cases chondrodysplasia Macrogyria pseudobulbar palsy 4 cases Leukoencephalopathy - palmoplantar 4 cases Macrophagic myofasciitis 1 keratoderma Macrostomia - preauricular tags - 9 cases Lewis-Pashayan syndrome 3 cases external ophthalmoplegia Lewis-Sumner syndrome 0,9 Malabsorptive diarrhea due to paucity 3 cases of enteroendocrine cells, congenital Lhermitte-Duclos disease 220 cases Malakoplasia 500 cases Lichstenstein syndrome 2 cases Malaria 3 Li-Fraumeni syndrome 400 families 33 Ligneous 1,1 Malignant hyperthermia - 4 cases Limb-mammary syndrome 27 cases arthrogryposis - torticollis Lipoamide dehydrogenase deficiency 20 cases Malonic aciduria 17 cases Lipodystrophy - mental retardation 3 cases 37 cases - deafness 3,9 Lipodystrophy, Berardinelli type 0,25 Marden-Walker syndrome 30 cases Lipodystrophy, familial partial, 10 cases associated with PPARG 30 Lipodystrophy, familial partial, due to 1 family Marie Unna congenital hypotrichosis 12 families AKT2 mutations Marinesco-Sjogren syndrome 200 cases Lipodystrophy, familial partial, 300 cases Marshall’s syndrome with periodic fever 30 cases Dunnigan type Marshall-Smith syndrome 33 cases Lipodystrophy, familial partial, < 20 cases Köbberling type Martinez monasterio pinheiro syndrome 1 case

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 14 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families MASA syndrome 3,5 Mental retardation, X-linked - Dandy 16 cases Walker malformation - Basal ganglia Maternal hyperphenylalaninemia 1,25 disease - Matthew-Wood syndrome 5 cases Mental retardation, X-linked - 8 cases Mayer-Rokitansky-Küster-Hauser 9 dysmorphism - cerebral atrophy syndrome Mental retardation, X-linked - epilepsy 2 cases Mazabraud syndrome 54 cases - progressive joint contractures - Mc Leod syndrome 150 cases dysmorphism McCune-Albright syndrome 158 cases Mental retardation, X-linked - 3 cases hypogammaglobulinemia - progressive Meckel syndrome 4** neurological deterioration Meconium aspiration syndrome 2,44 Mental retardation, X-linked - 4 cases Median cleft of the upper lip - corpus > 10 cases hypogonadism - ichthyosis - obesity callosum lipoma - cutaneous polyps - short stature Medullary cystic kidney disease, 0,11 Mental retardation, X-linked - 10 cases autosomal dominant, with or without - facial dysmorphism - aggressive behaviour Medullary cystic kidney disease, 1,05 Mental retardation, X-linked - 12 cases autosomal recessive macrocephaly - macro-orchidism Megacalycosis, congenital > 50 cases Mental retardation, X-linked - 2 cases Megacystis microcolon - intestinal 89 cases hypoperistalsis - Mental retardation, X-linked - seizures 4 cases - - - 6 cases post-axial polydactyly - hydrocephalus Mental retardation, X-linked - Spastic 1 family paraplegia with iron deposits MEHMO syndrome 7 cases Mental retardation, X-linked recessive 1 family MEHMO syndrome 7 cases - macrocephaly - ciliary dysfunction , familial 46,8 Mental retardation, X-linked, Abidi type 8 cases MELAS syndrome 16 Mental retardation, X-linked, Armfield 6 cases Melorheostosis 300 cases type Mendelian susceptibility to atypical 0,059 Mental retardation, X-linked, Cabezas 1 family mycobacteria type Meniere’s disease 42,5 Mental retardation, X-linked, Cantagrel 2 cases type Menkes syndrome 0,7 Mental retardation, X-linked, Lubs type 5 cases Mental retardation - dysmorphism - 4 cases hypogonadism - diabetes mellitus Mental retardation, X-linked, Miles- 4 cases Carpenter type Mental retardation - hypoplastic corpus 3 cases callosum - preauricular tag Mental retardation, X-linked, Pai type 1 family Mental retardation - progressive 1 family Mental retardation, X-linked, Reish type 2 cases spasticity, X-linked Mental retardation, X-linked, Schimke 4 cases Mental retardation sparse hair 6 cases type brachydactyly Mental retardation, X-linked, 4 cases Mental retardation X-linked - psychosis 6 cases Seemanova type - macroorchidism Mental retardation, X-linked, severe, 7 cases Mental retardation, X linked - 3 cases Gustavson type precocious puberty - obesity Mental retardation, X-linked, Shashi 9 cases Mental retardation, X linked, with 17 cases type seizures, short stature, and midface Mental retardation, X-linked, Shrimpton 3 cases hypoplasia type Mental retardation, X-linked - 2 cases Mental retardation, X-linked, Siderius 4 cases acromegaly - hyperactivity type Mental retardation, X-linked - 5 cases Mental retardation, X-linked, Snyder 11 cases choreoathetosis - abnormal behaviour type Mental retardation, X-linked - cubitus 5 cases Mental retardation, X-linked, South 16 cases valgus - dysmorphism African type

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 15 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Mental retardation, X-linked, Stevenson 4 cases Microcytic anaemia - liver 3 cases type - low ferritinemia Mental retardation, X-linked, Stocco 4 cases - type I microtia - deafness 9 cases Dos Santos type Microgastria - limb reduction defect 16 cases Mental retardation, X-linked, Stoll type 4 cases - micromelia 2 cases Mental retardation, X-linked, syndromic 10 cases Microphthalmia - brain atrophy 3 cases 7 Microscopic polyangiitis 7,5 Mental retardation, X-linked, < 10 families syndromic, due to JARID1C mutation Microtia 15 Mental retardation, X-linked, Vitale 8 cases Midas syndrome < 50 cases type Midline cleft of lower lip 70 cases Mental retardation, X-linked, Wilson 3 cases Miller-Dieker syndrome 0,3 type Mirhosseini-Holmes-Walton syndrome < 15 cases Mental retardation, X-linked, with 3 families isolated growth hormone deficiency Mitochondrial diseases of nuclear origin 9 Mental retardation, X-linked, Wittwer 3 cases Mitochondrial encephalomyopathy 2 cases type aminoacidopathy Mental retardation, X-linked, Zorick 6 cases Mitochondrial myopathy with 7 cases type sideroblastic anaemia MERRF syndrome 0,9 Mitral regurgitation - deafness - 3 cases skeletal anomalies Mesomelic dysplasia skin dimples 2 cases Mixed dystonias 3 families Metachromatic leukodystrophy 0,16 Moebius syndrome 300 cases Metaphyseal acroscyphodysplasia 4 cases Mohr-Tranebjaerg syndrome 46 cases Metaphyseal anadysplasia < 20 cases Monosomy 18p < 200 cases Metaphyseal chondrodysplasia, Jansen 16 cases type Monosomy 22q11 20 Metatropic dwarfism 80 cases Monosomy 22q13 > 200 cases Methimazole embryofetopathy 40 cases Monosomy 5p 4,6 Methylcobalamin deficiency type cbl E 27 cases Monosomy 9q22.3 2 cases Methylcobalamin deficiency type cbl G 33 cases Moore-Federman syndrome 6 cases Methylmalonic acidemia - 300 cases variegated syndrome 29 cases homocystinuria Mowat-Wilson syndrome < 200 cases Methylmalonic aciduria - microcephaly 2 cases Moya-moya disease 3,16 - cataract Mucocutaneous venous malformations 40 Methylmalonicacidemia - 300 cases homocystinuria, type cbl C Mucolipidosis type 2 0,15** Methylmalonicacidemia - 5 cases Mucolipidosis type 4 > 100 cases homocystinuria, type cbl D type 1 1,3 Methylmalonicaciduria - 9 cases Mucopolysaccharidosis type 2 0,6 homocystinuria, type cbl F Mucopolysaccharidosis type 3 1,1 Mevalonicaciduria 30 cases Mucopolysaccharidosis type 4 0,4 Michels syndrome 7 cases Mucopolysaccharidosis type 6 0,16** Micro syndrome 8 cases Mucopolysaccharidosis type 7 < 40 cases Microbrachycephaly - ptosis - cleft lip 2 cases Mucosulfatidosis 50 cases Microcephalic osteodysplastic 4 cases dysplasia, Saul-Wilson type Muenke syndrome 1,8** Microcephaly - cleft palate 3 cases Muir-Torre syndrome 205 cases Microcephaly - glomerulonephritis 2 cases MULIBREY nanism 115 cases - marfanoid habitus Mullerian derivatives - 3 cases Microcephaly - seizures - mental 2 cases lymphangiectasia - polydactyly retardation - heart disease Multifocal motor neuropathy with 1,5 Microcephaly cardiomyopathy 3 cases conduction block Microcephaly micropenis convulsions 4 cases Multiple endocrine neoplasia type 1 11

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 16 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Multiple endocrine neoplasia, type 2 3,3 N syndrome 3 cases Multiple fibrofolliculoma familial 7 cases N-acetyl-alpha-D-galactosaminidase 12 cases deficiency Multiple pterygium syndrome, 4 cases autosomal dominant Naegeli-Franceschetti-Jadassohn 0,035 syndrome Multiple pterygium syndrome, lethal 200 cases form Nail patella-like - renal disease 3 cases Multiple sclerosis - ichthyosis - factor 2 cases Nail-patella syndrome 2 8 deficiency Nance-Horan syndrome 50 families Multiple system atrophy 4,6 Nanism due to growth hormone 3 cases MURCS association 11,25 qualitative anomaly Muscular atrophy ataxia retinitis 10 cases NARP syndrome 8,5 pigmentosa diabetes mellitus Nasopalpebral lipoma - coloboma < 30 cases Muscular dystrophy congenital, with 0,03 - telecanthus integrin deficiency Nasopharyngeal dandy walker 1 case Muscular dystrophy Fukuyama type 0,54 diaphragmatic hernia Muscular dystrophy limb-girdle 0,8 Necrotizing encephalopathy, acute, 11 cases autosomal dominant Muscular dystrophy, congenital, non 0,15 merosin negative 1 Muscular dystrophy, congenital, type 0,3 Neonatal immune deficiency 5 cases 1A Neonatal hemochromatosis 100 cases Muscular dystrophy, Duchenne and 5 Nephroblastoma 10,1 Becker types Nephronophtisis familial, adult form 2 cases Muscular dystrophy, limb girdle, 14 cases - spastic quadriparesia autosomal recessive, type 2G Nephropathy - deafness - 5 cases Muscular dystrophy, limb girdle, > 40 families hyperparathyroidism autosomal recessive, type 2I Nephrosis deafness urinary tract digital 5 cases Muscular dystrophy, limb-girdle, 1 family malformations autosomal dominant, type 1A Nephrotic syndrome, idiopathic, 18 Muscular dystrophy, limb-girdle, 5 families -sensitive autosomal dominant, type 1D Netherton disease 1,35 Muscular dystrophy, limb-girdle, 5 families autosomal dominant, type 1E Neu-Laxova syndrome 60 cases Muscular dystrophy, limb-girdle, 1 family Neuroaxonal dystrophy renal tubular 3 cases autosomal dominant, type 1F acidosis Muscular dystrophy, limb-girdle, 1 family 10 autosomal dominant, type 1G Neurodegeneration due to 3- 4 cases Muscular dystrophy, tibial 6 hydroxyisobutyryl-CoA hydrolase deficiency Myasthenia gravis 8,5 Neurodegeneration due to 3- 2 cases Myasthenic , congenital 0,75 hydroxyisobutyryl-CoA hydrolase Myelodysplastic syndromes 25 deficiency Myelofibrosis with myeloid metaplasia 10 Neurodegenerative syndrome, X-linked, 7 cases Bertini type Myeloma, multiple 14,25 Neurodegenerative syndrome, X-linked, 10 cases Myhre syndrome 15 cases Hamel type Myoclonic epilepsy of infancy 106 cases Neuroectodermal endocrine syndrome 4 cases cerebellar ataxia deafness 4 cases type 1 25 Myoclonus hereditary - progressive < 10 cases Neurofibromatosis type 2 0,5 distal muscular atrophy Neurometabolic disorder due to serine < 30 cases Myoneurogastrointestinal 70 cases deficiency encephalopathy syndrome Neuropathy hereditary with liability to 9 Myopathy due to calsequestrin and 4 cases pressure palsies SERCA1 overload Neuropathy, giant axonal 20 families Myopathy, X-linked, with excessive 15 families autophagy Neutropenia cyclic 0,1

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 17 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Neutropenia severe congenital 0,4** Odonto-tricho-ungual-digito-palmarn 21 cases syndrome Neutropenia, severe congenital, X- 7 cases linked Okamoto syndrome 2 cases Nevo syndrome 10 cases Oligocone trichromacy 14 cases Nevus of ota retinitis pigmentosa 1 case Olmsted syndrome 32 cases Niemann-Pick disease 2,5** Omodysplasia 30 cases Niemann-Pick disease, type A 0,25** 12 Niemann-Pick disease, type B 0,75** Omphalocele cleft palate syndrome 3 cases lethal Niemann-Pick disease, type C 0,85 Ondine syndrome 2,25 Nijmegen breakage syndrome 1** Onycho-tricho-dysplasia - neutropenia 5 cases Nodular regenerative hyperplasia of 3 the liver Ophthalmo acromelic syndrome 30 cases Non-distal 10p 60 cases Opitz BBB/G syndrome 3 Non-distal trisomy 12p 2** 25 cases Non-distal trisomy 8q > 30 cases Optic atrophy 6 Non-Hodgkin malignant lymphoma 36 Optic atrophy and cataract, autosomal 14 cases dominant 300 cases Orbital leiomyoma 16 cases North Carolina macular dystrophy 2 families Ornithine carbamoyltransferase 1 Obesity - colitis - hypothyroidism 2 cases deficiency - cardiac hypertrophy - developmental delay Orofaciodigital syndrome, type 1 1,2 Obesity due to congenital leptin < 30 cases Orofaciodigital syndrome, type 10 1 case deficiency Orofaciodigital syndrome, type 3 3 cases Obesity due to prohormone convertase- 2 cases Orofaciodigital syndrome, type 4 16 cases I deficiency Orofaciodigital syndrome, type 5 4 cases Obesity due to pro-opiomelanocortin 7 cases deficiency Orofaciodigital syndrome, type 6 29 cases Ochoa syndrome > 100 cases Orofaciodigital syndrome, type 8 2 families X-linked, recessive 2 hereditary < 20 cases Ocular motor apraxia Cogan type 50 cases Ossification anomalies - psychomotor 2 cases development delay Oculocerebrocutaneous syndrome 36 cases dissecans 35 Oculocerebrofacial syndrome, Kaufman 9 cases type Osteochondrodysplatic nanism - 2 cases deafness - retinitis pigmentosa 7,15 Osteocraniostenosis 12 cases Oculodental syndrome Rutherfurd type 1 family Osteodysplasty, Melnick-Needles type > 50 cases Oculodentoosseous dysplasia dominant 243 cases 6,5 Oculodentoosseous dysplasia recessive 5 cases Osteogenesis imperfecta - retinopathy 2 cases Oculo-digito-esophageal-duodenal < 50 cases - seizures - intellectual deficit syndrome (ODED) Osteogenesis imperfecta, congenital 3 cases Oculogastrointestinal muscular 1 family - microcephaly - cataracts dystrophy Osteopathia striata - cranial sclerosis 100 cases Oculo-osteo-cutaneous syndrome 3 cases Osteopetrosis autosomal dominant 33 cases Oculo-oto-facial dysplasia 4 cases type 1 Oculo-palato-cerebral syndrome 5 cases Osteopetrosis, intermediate form 50 cases Oculopharyngeal muscular dystrophy 1 Osteopetrosis, malignant, autosomal 0,75** Oculo-tricho-dysplasia 2 cases recessive Odontomicronychial dysplasia 5 cases Osteopoikilosis - short stature - 4 cases Odonto-onycho-dermal dysplasia < 15 cases intellectual deficit Odonto-onycho-hypohidrotic dysplasia, 1 case Osteoporosis oculocutaneous 3 cases midline scalp defects hypopigmentation syndrome Odontotrichomelic syndrome 4 cases Osteoporosis pseudoglioma syndrome 0,05 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 18 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Osteosarcoma 5 Persistent hyperinsulinemic 2 of infancy - ichthyosis - premature 3 cases ovarian failure Persistent Mullerian duct syndrome < 200 cases Otodental syndrome 9 families Peters-plus syndrome 50 cases Otopalatodigital syndrome 30 cases Peutz-Jeghers syndrome 2,2 Overhydrated hereditary stomatocytosis 20 families 0,38 P2Y12, deficiency of 5 cases Pfeiffer-type cardiocranial syndrome < 10 cases Pachydermoperiostosis 204 cases PHACE syndrome 100 cases 230 cases Phaeochromocytoma and 10 paraganglioma, secreting Pacman dysplasia < 10 cases Phenylketonuria 4 Paget disease juvenile type 50 cases Phosphoenolpyruvate carboxykinase < 10 cases Pallister-Hall syndrome 100 cases (PEPCK) deficiency Palmoplantar keratoderma - amyotrophy 4 cases Phosphoglycerate kinase 1 deficiency 23 cases Palmoplantar keratoderma - XX sex 5 cases Phosphoribosylpyrophosphate < 30 families reversal - predisposition to squamous synthetase superactivity cell carcinoma Phytosterolemia 40 cases Palmoplantar of Mantoux < 10 cases PIBIDS syndrome 20 cases Pancreas agenesis 8 cases 0,25 Pancreatic hypoplasia - diabetes - heart < 10 cases disease Pierre Robin sequence, isolated 8,75 Pancreatic lipomatosis duodenal 1 case Pierson syndrome 22 cases stenosis Pili torti - onychodysplasia 1 family Pancreatitis, hereditary 0,125 Pilodental dysplasia with refractive 2 cases Pancreatoblastoma 60 cases errors Papillon-Lefevre syndrome 0,25 Pityriasis rubra pilaris 48 cases Papulosis, malignant atrophic > 200 cases Plummer-Vinson syndrome 25 cases Paraneoplastic > 60 cases of Kindler 100 cases Paraplegia - brachydactyly - cone- 5 cases Poland anomaly 2 shaped Pollitt syndrome 10 cases Paraplegia - mental retardation - 4 cases Polyarteritis nodosa 3,07 hyperkeratosis Polyarthritis, rheumatoid factor- 8 PARC syndrome 2 cases negative Parietal foramina 5 Polyarthritis, rheumatoid factor- 4,2 Parkinson disease, genetic types 15 positive Parkinsonism, young adult onset 37,5 Polycystic kidney disease, autosomal 6,5 recessive Paroxysmal extreme pain disorder 4 families Polycystic lipomembranous 0,15 Paroxysmal nocturnal hemoglobinuria 0,55 osteodysplasia with sclerosing Parsonage- 3,3 leukoencephalopathy Partington syndrome 2 families Polycystic - urethral sphincter 33 cases Pearson syndrome 60 cases dysfunction Pelizaeus-Merzbacher disease 0,25 Polycythemia vera 25 syndrome 11 cases Polydactyly preaxial 25 Pemphigus vulgaris 3,8 Polymorphic catecholergic ventricular 10 tachycardia Pendred syndrome 5,5 Polymyositis 14,8 Pericarditis arthropathy camptodactyly < 30 families syndrome Polysyndactyly - cardiac malformation 6 cases Perinatal-lethal Gaucher disease 0,01 Pontocerebellar hypoplasia type 1 6 families Peritoneal leiomyomatosis, 100 cases Pontocerebellar hypoplasia type 2 < 30 cases disseminated Porphyria, acute hepatic 8 < 20 cases Porphyria, chronic hepatic 1,5

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 19 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Porphyria, congenital erythropoietic > 200 cases Ptosis - - ectopic pupils 1 family Posterior column ataxia - retinitis 13 cases Ptosis - strabismus - rectus abdominis 2 cases pigmentosa diastasis Post-transplant lymphoproliferative 26,2 Pulmonary alveolar proteinosis 0,1 disease Pulmonary arterial hypertension 1,5 Potocki-Shaffer syndrome 23 cases Pulmonary fibrosis, idiopathic 27 Prader-Willi syndrome 10,7 Pulmonary haemosiderosis, primary 250 cases Preauricular pits renal disease 1 case Pulmonary lymphangiectasia, > 100 cases Primary biliary 13,5 congenital Primary ciliary dyskinesia 5 Pulmonary valve stenosis, congenital 7,2 Primary lateral sclerosis 1,5 Pure autonomic failure 0,1 Primary sclerosing cholangitis 11 Pyogenic arthritis - pyoderma 34 cases gangrenosum - 0,25** Pyruvate kinase deficiency 0,4 Progeria - short stature - pigmented < 10 cases nevi Qazi-Markouizos syndrome 3 cases Progressive bulbar paralysis of < 40 cases Radiation proctitis 35 childhood Radio-ulnar synostosis - < 20 cases Progressive neurodegeneration - joint 2 cases amegakaryocytic thrombocytopaenia laxity - cataract Rambaud galian syndrome 3 cases Progressive vertebral fusion, non- 10 cases < 20 cases infectious, syndromic form Rapid-onset dystonia-parkinsonism 3 families Progressive vertebral fusion, non- 10 cases infectious, syndromic form Rapp-Hodgkin syndrome 72 cases Prolidase deficiency 50 cases Rasmussen subacute encephalitis > 100 cases 3,75 Recurrent - short stature 4 cases - hypopigmentation - coarse face 200 cases Refsum disease 0,1 Protoporphyria, erythropoietic 0,9 Refsum disease, infantile form 0,005 Proximal myotonic myopathy 1 139 cases Proximal spinal muscular atrophy 3 Relapsing polychondritis 3,5 Proximal spinal muscular atrophy, type 0,26 1 Renal agenesis, bilateral 17 Proximal spinal muscular atrophy, type 2,6 Renal-hepatic-pancreatic dysplasia 10 cases 2 - Dandy-Walker cysts Proximal spinal muscular atrophy, type 2,6 Rendu-Osler-Weber disease 3,5 3 Renpenning syndrome 10 families Proximal spinal muscular atrophy, type 0,32 Restrictive cardiomyopathy, idiopathic 2,5 4 or familial Pseudoachondroplasia 3 Retinal , tortuosity of 100 cases Pseudoarthrosis of , congenital > 200 cases Retinal degeneration nanophthalmos 7 cases Pseudodiastrophic dysplasia 10 cases glaucoma type 1 70 cases Retinitis pigmentosa 27,5 Pseudoprogeria syndrome 2 cases Retinitis pigmentosa - intellectual 2 families deficit - deafness - hypogenitalism 2,5 Retinoblastoma 5,4 Pseudo- < 10 cases Retinohepatoendocrinologic syndrome 7 cases Psychomotor retardation due to 3 cases S-adenosylhomocysteine hydrolase , X-linked 4,5 deficiency 4,15 Pterygium colli - intellectual deficit 2 cases Rhabdoid tumors 500 cases - digital anomalies 5 Pterygium popliteal syndrome, 0,3 autosomal dominant Rheumatoid purpura 8,5 Pterygium syndrome, antecubital 11 cases 50 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 20 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Rickettsialpox > 800 cases Severe combined immunodeficiency due 0,22 to adenosine deaminase deficiency Rieger syndrome 0,5 Severe combined immunodeficiency 0,35 Ring 34 cases T- B- 10 < 20 cases Severe combined immunodeficiency 1,5 Ring chromosome 14 50 cases T- B+, X-linked Ring chromosome 17 14 cases Sezary’s syndrome 0,18 Ring 70 cases Short stature - pituitary and cerebellar 1 family Ring chromosome 20 > 50 cases defects - small sella turcica 100 cases Short stature - webbed - heart 4 cases disease Robinow-like syndrome 2 cases Short stature brussels type 2 cases Rolled and spiral - palmoplantar 4 cases keratoderma Short stature due to growth hormone 0,2 resistance Rothmund-Thomson syndrome 300 cases Short stature mental retardation eye 3 cases Rubella panencephalitis > 20 cases anomalies cleft lip palate Rubinstein-Taybi syndrome 1 SHORT syndrome 30 cases Rudiger syndrome 2 cases Shprintzen-Goldberg syndrome < 50 cases Sacral hemangiomas - multiple 5 cases Shwachman-diamond syndrome 200 cases congenital abnormalities Sialidosis type 1 0,02** Saethre-Chotzen syndrome 3 Sialidosis type 2 0,02** Sakati-Nyhan syndrome < 5 cases Sickle cell anaemia 11 Sandhoff disease 0,75 Siegler brewer carey syndrome 2 cases Sarcoidosis 15 Silent sinus syndrome 98 cases Sarcosinemia 2 Sillence syndrome 5 cases Say barber miller syndrome 2 cases Silver-Russell dwarfism 400 cases Scalp defects - postaxial polydactyly 2 cases Simpson-Golabi-Behmel syndrome > 100 cases Scalp-ear-nipple syndrome 30 cases Simpson-Golabi-Behmel syndrome, 4 cases SCARF syndrome 2 cases type 2 Schinzel syndrome < 10 families Singleton-Merten dysplasia < 10 cases Schinzel-Giedion midface retraction 34 cases 1** syndrome Sjögren-Larsson syndrome 0,4 1,54 Skeletal dysplasia - intellectual deficit 2 families Schizophrenia - mental retardation 1 family - deafness - retinitis Small vessel disease of the brain, not 2 cases NOTCH3-related Schnitzler syndrome 50 cases Smith-Lemli-Opitz syndrome 6,5 Schopf-Schulz-Passarge syndrome 19 cases Smith-Magenis syndrome 4 Schwartz-Jampel syndrome 100 cases Soft tissue sarcomas 13 Scleroderma 42 7** Sebastian syndrome < 10 families Sparse hair - short stature - skin 4 cases 100 cases anomalies Segmental odontomaxillary dysplasia 32 cases Spastic paraplegia - glaucoma - 2 families Seizures - intellectual deficit due to 3 cases intellectual deficit hydroxylysinuria Spastic paraplegia - nephritis - 4 cases Senior-Loken syndrome 0,1 deafness Sensenbrenner syndrome 15 cases Spastic paraplegia, familial 5 Sensorineural hearing loss, early 3 cases Spastic quadriplegia retinitis 2 cases greying, and essential tremor pigmentosa mental retardation Serpentine fibula polycystic kidneys 6 cases Spasticity - mental retardation - 6 cases epilepsy, X-linked Severe achondroplasia - developmental 4 cases delay - acanthosis nigricans Spherocytosis hereditary 20

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 21 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Spinal muscular atrophy - Dandy-Walker 2 cases Talo-patello-scaphoid osteolysis 2 cases complex - cataracts Tangier disease > 70 cases X-linked, type 3 5 cases Taurodontia - absent teeth - sparse hair < 15 cases Spinocerebellar ataxia, infantile onset 21 cases Tay-Sachs disease 0,3** Split hand - split foot 1,1 Terminal osseous dysplasia - 18 cases Split hand - split foot - deafness 22 cases pigmentary defects Split hand urinary anomalies spina 3 cases Tetraamelia - 5 families bifida Tetralogy of Fallot 45 Spondyloenchondrodysplasia 36 cases Thalidomide embryopathy 5000 cases Spondylometaphyseal dysplasia 0,34 Thanatophoric dwarfism 3,5** Spondylometaphyseal dysplasia - cone- 8 cases Thiamine-responsive megaloblastic 30 families rod dystrophy anaemia syndrome Spondylometaphyseal dysplasia with 4 cases Thomsen and Becker disease 5 combined immunodeficiency , essential 27,5 Spontaneous periodic < 30 cases Thrombocytopenic purpura, 25 Sporotrichosis 55 cases autoimmune Squamous cell carcinoma of head and 46 Thumb absent short stature immune 3 cases neck deficiency Stargardt disease 11,25 Thumb stiffness - brachydactyly - 6 cases Steinert 4,5 mental retardation < 2 Thymic renal anal lung dysplasia 3 cases Stern-Lubinsky-Durrie syndrome 7 cases Thyrocerebrorenal syndrome 2 cases Steroid dehydrogenase deficiency 1 family carcinoma, anaplastic 0,13 - dental anomalies Thyroid carcinoma, medullary 7 Stickler syndrome 13,5 Thyrotoxic periodic paralysis 2 Stiff-man syndrome 0,1 1 family Stimmler syndrome 2 cases 20 cases Stoll alembik finck syndrome 1 case Toriello-Carey syndrome 60 cases Subcorneal pustular dermatosis 200 cases Toriello-Lacassie-Droste syndrome 10 cases Succinic acidemia 50 cases Torticollis keloids renal 7 cases Succinyl-CoA acetoacetate transferase 10 cases dysplasia deficiency Townes-Brocks syndrome 0,42 Sucrase-isomaltase deficiency, 20 Tracheal agenesis 1** congenital < 100 cases Summitt syndrome 3 cases Superficial pemphigus 1,2 Transmissible spongiform 0,3 encephalopathies Supranuclear palsy, progressive 5 Transposition of the great arteries 32,5 Supravalvar 12,5 Treacher-Collins syndrome 6 Susac syndrome < 100 cases Treft-Sanborn-Carey syndrome 23 cases Symmetrical thalamic calcifications 29 cases Tricho oculo dermo vertebral syndrome 1 case Sympathetic ophthalmia 0,6 Tricho onycho hypohidrotic dysplasia 1 case Symphalangism distal < 5 families Trichodental syndrome < 5 families Symphalangism with multiple 6 cases anomalies of and feet Tricho-dento-osseous syndrome > 30 cases Synostoses, multiple 20 families Trichodysplasia - amelogenesis 1 family Synspondylism 24 cases imperfecta 8,4 Trichomegaly pigmentary 11 cases Systemic mastocytosis 0,33 degeneration dwarfism Systemic 6,3 Tricho-odonto-onychial dysplasia 4 cases Takayasu arteritis 0,45 Tricho-retino-dento-digital syndrome 9 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 22 Diseases name Estimated Number of Diseases name Estimated Number of prevalence published prevalence published (/100,000) cases or (/100,000) cases or families families Trichorhinophalangeal syndrome, type > 100 cases W syndrome 6 cases 1 and 3 2,4 Tricuspid atresia 5 Waardenburg-Shah syndrome 50 cases - bifid nose - acral 2 cases Waldenström macroglobulinemia 2,6 anomalies Walker-Warburg syndrome 1,65** Trigonocephaly - broad thumbs 2 cases 30 cases Trigonocephaly - short stature - 3 cases developmental delay Weaver- 2 cases Triose phosphate-isomerase deficiency 30 cases Wegener granulomatosis 6,6 Triphalangeal thumbs - 4 families Weill-Marchesani syndrome 128 cases brachyectrodactyly Wells syndrome 80 cases Triple A syndrome 100 cases 0,45 Triple H (HHH) syndrome 50 cases West syndrome 3,7** Triplo-X syndrome 42,5 Western equine encephalitis > 600 cases Trisomy 13 13** WHIM syndrome 40 cases Trisomy 18 9** Whipple disease 1000 cases Tritanopia 4,8 Wieacker-Wolff syndrome 6 cases True hermaphrodism > 500 cases Wiedemann-Rautenstrauch syndrome 25 cases Tuberculosis 20 Willebrand disease 12,5 8,8 Williams syndrome 13,3 Tubular renal disease - cardiomyopathy 2 cases Wilson disease 5,84 Tufted angioma > 200 cases Wilson-Turner syndrome > 14 cases Turner syndrome 20 Winchester disease 12 cases Tyrosinemia type 1 0,05 Wiskott-Aldrich syndrome 0,15 Tyrosinemia type 2 < 100 cases Wolcott-Rallison syndrome 17 cases Uhl anomaly 84 cases Wolf-Hirschhorn syndrome 2** Ulbright hodes syndrome 3 cases Wolfram syndrome 0,57 Ullrich, congenital muscular dystrophy < 100 cases Wolman disease 0,28** Ulnar / fibula ray defect - brachydactyly 1 family Woolly hair - hypotrichosis - everted 1 family Umbilical cord ulceration - intestinal 15 cases lower lip - outstanding ears atresia Woolly hair - palmoplantar keratoderma < 20 cases Unverricht-Lundborg disease 0,2 - Upington disease 1 family Wrinkly skin syndrome < 30 cases Usher syndrome 3,5 Xanthinuria 150 cases VACTERL with hydrocephalus < 10 families Xanthomatosis cerebrotendinous 0,13 Van den Bosch syndrome 1 family 0,5 2 Xeroderma talipes enamel defects 2 cases VATER association 23 XK aprosencephaly < 10 cases Vernal keratoconjunctivitis 10 X-linked dominant chondrodysplasia 0,5 punctata Visceral neuropathy - brain anomalies 2 cases X-linked lymphoproliferative disease 0,1 - facial dysmorphism - developmental delay Zellweger syndrome 1,1 Vitamin B12 responsive methylmalonic 60 cases Zellweger-like syndrome, without 2 cases acidemia, type cbl A peroxisomal anomalies Von Hippel-Lindau disease 0,2 Zollinger-Ellison syndrome 5,3 Vulvovaginal gingival syndrome 127 cases Zunich-Kaye syndrome 6 cases

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 23 Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 24 Prevalence of rare diseases : Bibliographic data Orphanet May 2008 Rep rt Series

Listed in order of decreasing prevalence or number of published cases

Method

A systematic survey of the literature is being performed in order to provide an estimate of the preva- lence of rare diseases in Europe. An updated report will be published regularly and will replace the previous version. This update contains new epidemiological data and modifications to existing data for which new information has been made available. Search strategy The search strategy is carried out using several data sources: - Websites: Orphanet, e-medicine, GeneClinics, EMEA and OMIM ; - Medline is consulted using the search algorithm: «Disease names» AND [Epidemiology[MeSH:NoExp] OR Incidence[Title/abstract] OR Prevalence[Title/abstract] OR Epidemiology[Title/abstract] ; - Medical books, grey literature and reports from experts are also important sources of data. Collected data Prevalence values provided are the mean of the highest and lowest values collected. When prevalence is not documented we calculate it using incidence: - For congenital diseases with birth-onset, prevalence = incidence at birth x (patient life expectancy/general population life expectancy) ; - For the other rare diseases, prevalence = incidence x rare disease mean duration ; When no prevalence or incidence data are available, the number of cases reported in the literature is provided. NB: Life expectancy of the French population (78 years) is used as the general population life expectancy. Updated Data New information from available data sources: EMEA, new scientific publications, grey literature, expert opinion. Limitation of the study The exact prevalence rate of each rare disease is difficult to assess from the available data sources. There is a low level of consistency between studies, a poor documentation of methods used, confusion between incidence and prevalence, and/or confusion between incidence at birth and life-long incidence. The validity of the published studies is taken for granted and not assessed. It is likely that there is an overestimation for most diseases as the few published prevalence surveys are usually done in regions of higher prevalence and are usually based on hospital data. Therefore, these estimates are an indication of the assumed prevalence but may not be accurate.

For any questions or comments, please contact us: [email protected] Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  List of diseases by decreasing prevalence Diseases with prevalence data available

Diseases name Estimated Diseases name Estimated prevalence prevalence (/100,000) (/100,000) Cutaneous lupus erythematosus 50 Legg-Calve-Perthes disease 23 Gelineau disease 49 VATER association 23 Melanoma, familial 46,8 Arthritis, oligoarticular juvenile 20,5 Squamous cell carcinoma of head and neck 46 Dermatitis herpetiformis 20,2 Autism 45 Atresia of small intestine 20 Tetralogy of Fallot 45 Atrioventricular canal, partial 20 Arrhythmogenic right ventricular dysplasia 43,5 Gastric cancer 20 Meniere’s disease 42,5 Hirschsprung disease 20 Triplo-X syndrome 42,5 Monosomy 22q11 20 Chromosome Y deletion 42 Spherocytosis hereditary 20 Scleroderma 42 Sucrase-isomaltase deficiency, congenital 20 Fetal cytomegalovirus syndrome 40 Tuberculosis 20 Mucocutaneous venous malformations 40 Turner syndrome 20 Parkinsonism, young adult onset 37,5 Corpus callosum agenesis neuronopathy 19 36 Nephrotic syndrome, idiopathic, steroid-sensitive 18 Non-Hodgkin malignant lymphoma 36 Cardiomyopathy, familial dilated 17,5 Elliptocytosis, hereditary 35 Boutonneuse fever 17 Osteochondritis dissecans 35 Renal agenesis, bilateral 17 Radiation proctitis 35 Ichthyosis, X-linked 16,6 Adactylia unilateral 34 MELAS syndrome 16 Cryptosporidiosis 34 Leucinosis 15,6 Malignant hyperthermia 33 Acyl-CoA dehydrogenase, medium chain, deficiency of 15 Charcot-Marie-Tooth disease 32,5 Atrioventricular canal, complete 15** Transposition of the great arteries 32,5 Diaphragmatic hernia, congenital 15 B-cell chronic lymphocytic leukaemia 32 Lennox-Gastaut syndrome 15 Acute Respiratory Distress Syndrome, Adult 30 Microtia 15 Arthrogryposis multiplex congenita 30 Parkinson disease, genetic types 15 Marfan syndrome 30 Sarcoidosis 15 Hypothyroidism, congenital 29 Dermatomyositis 14,8 Retinitis pigmentosa 27,5 Polymyositis 14,8 Thrombocythemia, essential 27,5 Fragile X syndrome 14,25 Pulmonary fibrosis, idiopathic 27 Myeloma, multiple 14,25 Post-transplant lymphoproliferative disease 26,2 Anophthalmia - Microphthalmia, isolated 14 Alpha-1 antitrypsin deficiency 25 Cystinuria 14 Breast cancer, familial 25 Primary biliary cirrhosis 13,5 Esophageal atresia 25 Stickler syndrome 13,5 Long QT syndrome, familial 25 Williams syndrome 13,3 Myelodysplastic syndromes 25 Androgen insensitivity syndrome 13 Neurofibromatosis type 1 25 Bronchopulmonary dysplasia 13 Polycythemia vera 25 Gastrointestinal stromal tumor 13 Polydactyly preaxial 25 Soft tissue sarcomas 13 Thrombocytopenic purpura, autoimmune 25 Trisomy 13 13** Anorectal malformation 24 Buerger’s disease 12,5

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  Diseases name Estimated Diseases name Estimated prevalence prevalence (/100,000) (/100,000) Ehlers-Danlos syndrome type 3 12,5 Rheumatoid purpura 8,5 Supravalvar aortic stenosis 12,5 Syringomyelia 8,4 Willebrand disease 12,5 Cutaneous 8,3 Cystic fibrosis 12 Acute promyelocytic leukaemia 8 Gastroschisis 12 Esophageal carcinoma 8 Gonadal dysgenesis, XX type 12 Polyarthritis, rheumatoid factor-negative 8 Omphalocele 12 Porphyria, acute hepatic 8 Focal dystonia 11,7 Hyperlipidemia type 3 7,8 MURCS association 11,25 Hemophilia 7,7 Stargardt disease 11,25 Kallmann syndrome 7,7 Glioblastoma 11 Acute lymphoblastic leukaemia 7,5 Hepatic venoocclusive disease 11 Immunodeficiency, common variable 7,5 Multiple endocrine neoplasia type 1 11 Microscopic polyangiitis 7,5 Primary sclerosing cholangitis 11 Beckwith-Wiedemann syndrome 7,3 Sickle cell anaemia 11 Pulmonary valve stenosis, congenital 7,2 Prader-Willi syndrome 10,7 Oculocutaneous albinism 7,15 Alopecia totalis 10,5 Acute non lymphoblastic leukaemia 7 10,5 Cerebellar ataxia, autosomal recessive 7 Hodgkin lymphoma, classical 10,5 Cystathioninuria 7 Nephroblastoma 10,1 Facioscapulohumeral muscular dystrophy 7 3-methylglutaconic aciduria, type 3 10 Fryns syndrome 7** Achalasia, primary 10 Holoprosencephaly 7 Adrenal hyperplasia, congenital 10 Sotos syndrome 7** Amaurosis congenita of Leber 10 Thyroid carcinoma, medullary 7 Bone tumor 10 Iminoglycinuria 6,68 Cholangiocarcinoma 10 Cat-scratch disease 6,6 Dermatofibrosarcoma protuberans 10 Galactosemia 6,6 Distal myopathy, Welander type 10 Wegener granulomatosis 6,6 Duane syndrome 10 Angelman syndrome 6,5 Factor II deficiency 10 Carcinoma of the gallbladder 6,5 Idiopathic hypereosinophilic syndrome 10 Hemiplegic migraine, familial 6,5 Lung cancer, small cell 10 Leber hereditary optic neuropathy 6,5 Myelofibrosis with myeloid metaplasia 10 Osteogenesis imperfecta 6,5 Neuroblastoma 10 Polycystic kidney disease, autosomal recessive 6,5 Phaeochromocytoma and paraganglioma, secreting 10 Smith-Lemli-Opitz syndrome 6,5 Polymorphic catecholergic ventricular tachycardia 10 Ectopia lentis isolated 6,4 Vernal keratoconjunctivitis 10 Arthritis, systemic-onset, juvenile idiopathic 6,3 Mayer-Rokitansky-Küster-Hauser syndrome 9 Systemic vasculitis 6,3 Mitochondrial diseases of nuclear origin 9 Huntington disease 6,2 Neuropathy hereditary with liability to pressure palsies 9 Amyotrophic lateral sclerosis 6 Trisomy 18 9** Cerebral arteriovenous fistula 6 8,9 Digitotalar dysmorphism 6 Lymphoedema, congenital 8,8 Leukaemia, chronic myeloid 6 Tuberous sclerosis 8,8 Muscular dystrophy, tibial 6 , isolated 8,75 Optic atrophy 6 Duodenal atresia 8,55 Treacher-Collins syndrome 6 Myasthenia gravis 8,5 Wilson disease 5,84 NARP syndrome 8,5 Arthritis, enthesitis-related 5,7

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  Diseases name Estimated Diseases name Estimated prevalence prevalence (/100,000) (/100,000) Biliary atresia 5,6 Calpainopathy 3,8 Pendred syndrome 5,5 Pemphigus vulgaris 3,8 Retinoblastoma 5,4 Propionic acidemia 3,75 Alzheimer disease, familial 5,3 West syndrome 3,7** Zollinger-Ellison syndrome 5,3 Diastrophic dwarfism 3,5 Cornelia de Lange syndrome 5,25 Ehlers-Danlos syndrome, classic type 3,5 Familial adenomatous polyposis 5,25 Goldenhar syndrome 3,5 Acromegaly 5 MASA syndrome 3,5 Adrenoleukodystrophy, X-linked 5 Relapsing polychondritis 3,5 Epiphyseal dysplasia multiple 5 Rendu-Osler-Weber disease 3,5 Fructose intolerance 5 Thanatophoric dwarfism 3,5** Hydrolethalus 5** 3,5 Muscular dystrophy, Duchenne and Becker types 5 Guillain-Barré syndrome 3,45 Osteosarcoma 5 Graft versus host disease 3,4 Parietal foramina 5 Choroidal dystrophy, central areolar 3,33 Primary ciliary dyskinesia 5 Hypochondroplasia 3,3 Rheumatic fever 5 Multiple endocrine neoplasia, type 2 3,3 Spastic paraplegia, familial 5 Parsonage-Turner syndrome 3,3 Supranuclear palsy, progressive 5 Anencephaly 3,2** Thomsen and Becker disease 5 Moya-moya disease 3,16 Tricuspid atresia 5 Acatalasemia 3,1 Tritanopia 4,8 Polyarteritis nodosa 3,07 Acrocephalosyndactyly 4,6 Bacterial toxic-shock syndrome 3 Monosomy 5p 4,6 Frontotemporal dementia 3 Multiple system atrophy 4,6 Malaria 3 Achondroplasia 4,5 Nodular regenerative hyperplasia of the liver 3 Congenital lobar emphysema 4,5 Opitz BBB/G syndrome 3 Retinoschisis, X-linked 4,5 Proximal spinal muscular atrophy 3 Steinert myotonic dystrophy 4,5 Pseudoachondroplasia 3 Best disease 4,4 Saethre-Chotzen syndrome 3 Chronic inflammatory demyelinating polyneuropathy 4,4 Kennedy disease 2,8 Arthritis, juvenile psoriatic 4,2 Leigh syndrome 2,75** Polyarthritis, rheumatoid factor-positive 4,2 Proximal spinal muscular atrophy, type 2 2,6 Hemimelia 4,15 Proximal spinal muscular atrophy, type 3 2,6 Rett syndrome 4,15 Waldenström macroglobulinemia 2,6 Amniotic bands 4** Behcet disease 2,5 Autoimmune polyendocrinopathy, type 1 4 BOR syndrome 2,5 Ceroid lipofuscinosis, neuronal 4 Bullous pemphigoid 2,5 Corticobasal degeneration 4 Cone rod dystrophy 2,5 Hartnup syndrome 4 Diffuse palmoplantar keratoderma, Norrbotten dominant 2,5 type Histidinemia 4 Epidermolysis bullosa, epidermolytic 2,5 Idiopathic hypersomnia 4 Friedreich ataxia 2,5 Meckel syndrome 4** Fructose-1,6-bisphosphatase deficiency 2,5 Phenylketonuria 4 Smith-Magenis syndrome 4 Heterotaxia 2,5 Mantle cell lymphoma 3,9 Niemann-Pick disease 2,5** Acute interstitial pneumonia 3,8 Pseudoxanthoma elasticum 2,5 Anisakiasis 3,8 Restrictive cardiomyopathy, idiopathic or familial 2,5

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  Diseases name Estimated Diseases name Estimated prevalence prevalence (/100,000) (/100,000) Meconium aspiration syndrome 2,44 Severe combined immunodeficiency T- B+, X-linked 1,5 Waardenburg syndrome 2,4 Alagille syndrome 1,4 3-methylcrotonylglycinuria 2,25 Cat-eye syndrome 1,35 Ondine syndrome 2,25 Netherton disease 1,35 Peutz-Jeghers syndrome 2,2 Cryoglobulinemia 1,33* Cerebellar ataxia, autosomal dominant 2,15 Mucopolysaccharidosis type 1 1,3 GRACILE syndrome 2,12** Apert syndrome 1,25 Alport syndrome 2 Maternal hyperphenylalaninemia 1,25 Choroideremia 2 Adult Onset Still’s disease 1,23 Coats disease 2 Orofaciodigital syndrome, type 1 1,2 Crouzon disease 2 Superficial pemphigus 1,2 Exostoses, multiple 2 Kabuki syndrome 1,16 Gaucher disease 2 Glycogen storage disease type 2 1,1 Giant pigmented hairy nevus 2 Ligneous conjunctivitis 1,1 Kearns-Sayre syndrome 2 Mucopolysaccharidosis type 3 1,1 Klippel-Feil syndrome 2 Split hand - split foot 1,1 Langerhans cell histiocytosis 2 Zellweger syndrome 1,1 Lateral body wall complex 2** Medullary cystic kidney disease, autosomal recessive 1,05 Nail-patella syndrome 2 Cutis verticis gyrata - mental deficit 1,02 Non-distal trisomy 12p 2** 3-hydroxyacyl-CoA dehydrogenase, long chain, 1 deficiency of Ocular albinism X-linked, recessive 2 Acanthamoeba keratitis 1 Persistent hyperinsulinemic hypoglycemia of infancy 2 Adrenocortical carcinoma 1 Poland anomaly 2 Albers-Schonberg disease 1 Sarcosinemia 2 Angioedema 1 Thyrotoxic periodic paralysis 2 Ataxia telangiectasia 1 Van Der Woude syndrome 2 Chondrodysplasia punctata, rhizomelic type 1 Wolf-Hirschhorn syndrome 2** Chronic hiccup 1 Sternal cleft < 2 Churg-Strauss syndrome 1 Gamma-sarcoglycanopathy 1,96 Clouston syndrome 1 Muenke syndrome 1,8** Coloboma, ocular 1 Amoebiasis due to free-living amoebae 1,75 Congenital rubella syndrome 1** Aniridia 1,75 Crigler-Najjar syndrome 1 Fabry disease 1,75 Dyserythropoietic anaemia, congenital 1 2,8 dihydroxyadenine urolithiasis 1,7 Kaposi’s sarcoma 1,7 Ehlers-Danlos syndrome type 4 1 Walker-Warburg syndrome 1,65** Endocrine tumour 1 Charcot-Marie-Tooth disease, X-linked 1,6 Fanconi anaemia 1 Schizencephaly 1,54 Gorlin syndrome 1 Antisynthetase syndrome 1,5 Harding ataxia 1 Budd-Chiari syndrome 1,5 Holt-Oram syndrome 1 CDG syndrome 1,5** Hypokalemic periodic paralysis 1 Darier disease 1,5 Isovaleric acidemia 1 Femur-fibula-ulna complex 1,5 Lambert-Eaton myasthenic syndrome 1 Laryngo-tracheo-esophageal cleft 1,5 Macrophagic myofasciitis 1 Multifocal motor neuropathy with conduction block 1,5 Nemaline myopathy 1 Porphyria, chronic hepatic 1,5 Nijmegen breakage syndrome 1** Primary lateral sclerosis 1,5 Oculopharyngeal muscular dystrophy 1 Pulmonary arterial hypertension 1,5 Ornithine carbamoyltransferase deficiency 1

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  Diseases name Estimated Diseases name Estimated prevalence prevalence (/100,000) (/100,000) Proximal myotonic myopathy 1 Cowden syndrome 0,45 Rubinstein-Taybi syndrome 1 Takayasu arteritis 0,45 Sirenomelia 1** Werner syndrome 0,45 Tracheal agenesis 1** Townes-Brocks syndrome 0,42 < 1** Aplastic anaemia 0,4 Gaucher disease type 1 0,94 Bullous ichthyosiform erythroderma congenita 0,4 Lewis-Sumner syndrome 0,9 Early onset torsion dystonia 0,4 MERRF syndrome 0,9 Glutaryl-CoA dehydrogenase deficiency 0,4 Protoporphyria, erythropoietic 0,9 Homocystinuria due to cystathionine beta-synthase 0,4 deficiency Joubert syndrome 0,85 Mucopolysaccharidosis type 4 0,4 Niemann-Pick disease, type C 0,85 Neutropenia severe congenital 0,4** Bardet-Biedl syndrome 0,8 Pyruvate kinase deficiency 0,4 Criss-cross heart 0,8 Sjögren-Larsson syndrome 0,4 Muscular dystrophy limb-girdle 0,8 Lesch-Nyhan syndrome 0,38 Cutaneous mastocytosis 0,75 Pfeiffer syndrome 0,38 Ebstein anomaly 0,75 Campomelic dysplasia 0,35 Hepatitis, chronic autoimmune 0,75 Christ-Siemens-Touraine syndrome 0,35 Hyperkalemic periodic paralysis 0,75 Severe combined immunodeficiency T- B- 0,35 Krabbe disease 0,75** Spondylometaphyseal dysplasia 0,34 Myasthenic syndromes, congenital 0,75 Lamellar ichthyosis > 0,33 Niemann-Pick disease, type B 0,75** Systemic mastocytosis 0,33 Osteopetrosis, malignant, autosomal recessive 0,75** Blackfan-Diamond disease 0,32 Sandhoff disease 0,75 Proximal spinal muscular atrophy, type 4 0,32 Albright hereditary osteodystrophy 0,72 Alkaptonuria 0,3 Carbamoylphosphate synthetase deficiency 0,7 Aortic arch interruption 0,3** Menkes syndrome 0,7 Dopa-responsive dystonia 0,3 Goodpasture syndrome 0,64 Emery-Dreifuss muscular dystrophy 0,3 Glycogen storage disease type 4 0,6 Miller-Dieker syndrome 0,3 Hyperlipoproteinemia type 1 0,6 Muscular dystrophy, congenital, type 1A 0,3 Mucopolysaccharidosis type 2 0,6 Pterygium popliteal syndrome, autosomal dominant 0,3 Sympathetic ophthalmia 0,6 Tay-Sachs disease 0,3** Alpha-sarcoglycanopathy 0,57 Beta-sarcoglycanopathy 0,57 Transmissible spongiform encephalopathies 0,3 Delta-sarcoglycanopathy 0,57 Dentatorubral pallidoluysian atrophy < 0,3 Wolfram syndrome 0,57 Wolman disease 0,28** Cantrell pentalogy 0,55** Epidermolysis bullosa, dystrophic 0,27 Coffin-Lowry syndrome 0,55 Proximal spinal muscular atrophy, type 1 0,26 Paroxysmal nocturnal hemoglobinuria 0,55 Factor VII deficiency 0,25 Muscular dystrophy Fukuyama type 0,54 Lipodystrophy, Berardinelli type 0,25 Cutaneous neuroendocrine carcinoma 0,5 Niemann-Pick disease, type A 0,25** Cystinosis 0,5 Papillon-Lefevre syndrome 0,25 Diabetes insipidus, nephrogenic 0,5 Pelizaeus-Merzbacher disease 0,25 Neurofibromatosis type 2 0,5 Piebaldism 0,25 Rieger syndrome 0,5 Progeria 0,25** Xeroderma pigmentosum 0,5 Leptospirosis 0,24 X-linked dominant chondrodysplasia punctata 0,5 Severe combined immunodeficiency due to adenosine 0,22 Inclusion body myositis, IBM 0,49 deaminase deficiency Agammaglobulinemia X-linked 0,45 Acrodermatitis enteropathica, zinc deficiency type 0,2

** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  Diseases name Estimated Diseases name Estimated prevalence prevalence (/100,000) (/100,000) Diabetes mellitus, neonatal 0,2 Ewing sarcoma 0,1 Granulomatous disease, chronic 0,2 Factor V deficiency 0,1 Hyperglycinemia, isolated nonketotic 0,2 Factor XI deficiency, congenital 0,1 Hyperoxaluria 0,2 Familial cold urticaria 0,1 Incontinentia pigmenti 0,2 Hemophilia, acquired 0,1 Jeune syndrome 0,2 Leprechaunism 0,1** Short stature due to growth hormone resistance 0,2 Lymphangioleiomyomatosis 0,1 Unverricht-Lundborg disease 0,2 Neutropenia cyclic 0,1 Von Hippel-Lindau disease 0,2 Pulmonary alveolar proteinosis 0,1 Lowe syndrome 0,19 Pure autonomic failure 0,1 Sezary’s syndrome 0,18 Refsum disease 0,1 Atypical coarctation of aorta 0,17** Senior-Loken syndrome 0,1 Metachromatic leukodystrophy 0,16 Stiff-man syndrome 0,1 Mucopolysaccharidosis type 6 0,16** X-linked lymphoproliferative disease 0,1 Epilepsy, pyridoxin-dependent 0,15 Lafora disease < 0,1 Fibrinogen deficiency, congenital 0,15 Fibrodysplasia ossificans progressiva 0,08 Hermansky-Pudlak syndrome 0,15 Epidermolysis bullosa, junctional 0,06 Mucolipidosis type 2 0,15** Mendelian susceptibility to atypical mycobacteria 0,059 Muscular dystrophy, congenital, non merosin negative 0,15 Aceruloplasminemia 0,05 Polycystic lipomembranous osteodysplasia with 0,15 Botulism 0,05 sclerosing leukoencephalopathy Chordoma 0,05 Wiskott-Aldrich syndrome 0,15 Craniofacial dyssynostosis 0,05 CHARGE association 0,14 Gaucher disease type 3 0,05 Thyroid carcinoma, anaplastic 0,13 Osteoporosis pseudoglioma syndrome 0,05 Xanthomatosis cerebrotendinous 0,13 Tyrosinemia type 1 0,05 Pancreatitis, hereditary 0,125 Fibrous dysplasia of bone < 0,05 Bartter syndrome 0,12 Factor XIII deficiency, congenital 0,04 Lissencephaly type 2 0,12 Naegeli-Franceschetti-Jadassohn syndrome 0,035 Medullary cystic kidney disease, autosomal dominant, 0,11 Muscular dystrophy congenital, with integrin deficiency 0,03 with or without hyperuricemia Alpers syndrome 0,025 Alpha-mannosidosis 0,1 Sialidosis type 1 0,02** Creutzfeldt-Jakob disease 0,1 Diffuse leiomyomatosis - Alport syndrome X-linked 0,1 Sialidosis type 2 0,02** Distal myopathy, Nonaka type 0,1 Gaucher disease type 2 0,01 Dyskeratosis congenita 0,1 Perinatal-lethal Gaucher disease 0,01 Evans syndrome 0,1 Refsum disease, infantile form 0,005 ** Prevalence at birth

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  List of diseases by reported number of published cases Diseases without prevalence data available. Report on number of published cases

Diseases name Number of Diseases name Number of published cases published cases or families or families Thalidomide embryopathy 5000 cases Lhermitte-Duclos disease 220 cases Angio-osteohypertrophic syndrome 1000 cases Muir-Torre syndrome 205 cases Whipple disease 1000 cases 204 cases Alveolar echinococcosis < 1000 cases Aarskog-Scott syndrome > 200 cases Esthesioneuroblastoma < 1000 cases Blue rubber bleb nevus > 200 cases Rickettsialpox > 800 cases Erythrokeratodermia variabilis, Mendes da Costa > 200 cases type Fetal methyl mercury syndrome 800 cases Monosomy 22q13 > 200 cases Western equine encephalitis > 600 cases Papulosis, malignant atrophic > 200 cases Enchondromatosis 600 cases Porphyria, congenital erythropoietic > 200 cases Familial dysautonomia 550 cases Pseudoarthrosis of clavicle, congenital > 200 cases Adamantinoma 513 cases Tufted angioma > 200 cases True hermaphrodism > 500 cases Adenosine monophosphate deaminase deficiency 200 cases CADASIL 500 cases 200 cases Malakoplasia 500 cases Camurati engelmann disease 200 cases Rhabdoid tumors 500 cases Cockayne syndrome 200 cases Epidermal nevus syndrome > 400 cases Cogan syndrome 200 cases Castleman disease 400 cases Costello syndrome 200 cases Silver-Russell dwarfism 400 cases Eosinophilic fasciitis 200 cases 4-hydroxybutyricaciduria 350 cases Glucose-galactose malabsorption 200 cases Leukocyte adhesion deficiency (LAD) < 350 cases Gorham-Stout disease 200 cases Alexander disease 300 cases Kimura disease 200 cases Alström syndrome 300 cases Marinesco-Sjogren syndrome 200 cases CDG syndrome type Ia 300 cases Multiple pterygium syndrome, lethal form 200 cases Cutis marmorata telangiectatica congenita 300 cases Proteus syndrome 200 cases Focal dermal hypoplasia 300 cases Shwachman-diamond syndrome 200 cases Gräsbeck-Imerslund disease 300 cases Subcorneal pustular dermatosis 200 cases Lipodystrophy, familial partial, Dunnigan type 300 cases Monosomy 18p < 200 cases Melorheostosis 300 cases Mowat-Wilson syndrome < 200 cases Methylmalonic acidemia - homocystinuria 300 cases Persistent Mullerian duct syndrome < 200 cases Methylmalonicacidemia - homocystinuria, type 300 cases cbl C Hyperimmunoglobinemia D with recurrent fever 180 cases Moebius syndrome 300 cases Erdheim-Chester disease 178 cases Norrie disease 300 cases Kasabach-Merritt syndrome > 175 cases Rothmund-Thomson syndrome 300 cases Celiac disease epilepsy occipital calcifications 170 cases Lipoid proteinosis > 280 cases Alpha thalassemia- mental retardation, X-linked 168 cases Eosinophilic gastroenteritis 280 cases Carney complex 160 cases Chronic recurrent multifocal osteomyelitis, juvenile > 260 cases McCune-Albright syndrome 158 cases Job syndrome 250 cases Infantile neuroaxonal dystrophy > 150 cases Lipodystrophy, partial acquired 250 cases Cloverleaf skull syndrome 150 cases Pulmonary haemosiderosis, primary 250 cases Denys-Drash syndrome 150 cases Caroli’s disease < 250 cases Dubowitz syndrome 150 cases 6-pyruvoyl-tetrahydropterin synthase, deficiency 248 cases Ellis Van Creveld syndrome 150 cases Oculodentoosseous dysplasia dominant 243 cases Fraser syndrome 150 cases Pachyonychia congenita 230 cases Humeroradial synostosis 150 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  Diseases name Number of Diseases name Number of published cases published cases or families or families Jacobsen syndrome 150 cases Peritoneal leiomyomatosis, disseminated 100 cases Mc Leod neuroacanthocytosis syndrome 150 cases PHACE syndrome 100 cases 150 cases Poikiloderma of Kindler 100 cases Arthrogryposis - renal dysfunction - cholestasis < 150 cases Retinal arteries, tortuosity of 100 cases Inflammatory pseudotumor of the liver 143 cases Roberts syndrome 100 cases Regional odontodysplasia 139 cases Schwartz-Jampel syndrome 100 cases Dihydropteridine reductase deficiency 134 cases Seckel syndrome 100 cases Aorto-ventricular tunnel 130 cases Triple A syndrome 100 cases Weill-Marchesani syndrome 128 cases Brown-Vialetto-van Laere syndrome < 100 cases Vulvovaginal gingival syndrome 127 cases Hallermann-Streiff-Francois syndrome < 100 cases MULIBREY nanism 115 cases Hypertrichosis lanuginosa congenita < 100 cases Bickel-Fanconi glycogenosis 112 cases Hypocomplementaemic leucocytoclasic vasculitis < 100 cases Myoclonic epilepsy of infancy 106 cases Ichthyosis congenita, harlequin type < 100 cases Achondrogenesis > 100 cases Susac syndrome < 100 cases Bloom syndrome > 100 cases Tracheobronchomegaly < 100 cases Carnitine palmitoyl transferase 2 deficiency > 100 cases Tyrosinemia type 2 < 100 cases Central neurocytoma > 100 cases Ullrich, congenital muscular dystrophy < 100 cases Cutis laxa > 100 cases Silent sinus syndrome 98 cases Eosinophilic pneumonia, acute idiopathic > 100 cases Acrofacial dysostosis, Nager type 90 cases Fetal varicella syndrome > 100 cases Megacystis microcolon - intestinal hypoperistalsis 89 cases - hydronephrosis KID syndrome > 100 cases Early infantile epileptic encephalopathy 88 cases Mucolipidosis type 4 > 100 cases Glycogen storage disease due to LAMP-2 deficiency 84 cases Ochoa syndrome > 100 cases Uhl anomaly 84 cases Pulmonary lymphangiectasia, congenital > 100 cases Acquired generalized lipodystrophy 80 cases Rasmussen subacute encephalitis > 100 cases Metatropic dwarfism 80 cases Simpson-Golabi-Behmel syndrome > 100 cases Wells syndrome 80 cases Trichorhinophalangeal syndrome, type 1 and 3 > 100 cases Rapp-Hodgkin syndrome 72 cases Aicardi-Goutieres syndrome 100 cases LEOPARD syndrome > 70 cases Autoimmune lymphoproliferative syndrome 100 cases Tangier disease > 70 cases Bernard-Soulier syndrome 100 cases Bullous systemic lupus erythematosus 70 cases Bethlem myopathy 100 cases Craniometaphyseal dysplasia 70 cases Chaotic atrial tachycardia 100 cases Midline cleft of lower lip 70 cases CINCA syndrome 100 cases Myoneurogastrointestinal encephalopathy 70 cases Cohen syndrome 100 cases syndrome Congenital cataracts - facial dysmorphism - 100 cases Pseudohypoaldosteronism type 1 70 cases neuropathy 70 cases Defective expression of HLA class 2 100 cases Diffuse neonatal haemangiomatosis < 70 cases Epidermolysis bullosa, acquired 100 cases Glutathione synthetase deficiency 65 cases Freeman-Sheldon syndrome 100 cases Hyperferritinemia, hereditary, with congenital > 64 cases Fucosidosis 100 cases cataracts Greig syndrome 100 cases Paraneoplastic pemphigus > 60 cases Helicoid peripapillary chorioretinal degeneration 100 cases Cerebro-costo-mandibular syndrome 60 cases Immunodeficiency due to selective anti- 100 cases Dyggve-Melchior-Clausen disease 60 cases polysaccharide antibody deficiency Griscelli disease 60 cases Internal carotid agenesis 100 cases Hypertrichosis lanuginosa, acquired 60 cases Larsen syndrome 100 cases Ketoacidosis due to betaketothiolase deficiency 60 cases Neonatal hemochromatosis 100 cases Neu-Laxova syndrome 60 cases Osteopathia striata - cranial sclerosis 100 cases Non-distal trisomy 10p 60 cases Pallister-Hall syndrome 100 cases Pancreatoblastoma 60 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf  Diseases name Number of Diseases name Number of published cases published cases or families or families Pearson syndrome 60 cases Midas syndrome < 50 cases Toriello-Carey syndrome 60 cases Oculo-digito-esophageal-duodenal syndrome < 50 cases (ODED) Vitamin B12 responsive methylmalonic acidemia, 60 cases type cbl A Shprintzen-Goldberg syndrome < 50 cases Double uterus-hemivagina-renal agenesis < 60 cases Corticosteroid-sensitive aseptic abscesses 49 cases Ataxia, autosomal recessive, Beauce type 57 cases Pityriasis rubra pilaris 48 cases Capillary leak syndrome 57 cases Coxo-podo-patellar syndrome 47 cases Sporotrichosis 55 cases Mohr-Tranebjaerg syndrome 46 cases Mazabraud syndrome 54 cases Encephalo cranio cutaneous lipomatosis 45 cases Hennekam syndrome > 50 cases KBG syndrome 45 cases Megacalycosis, congenital > 50 cases Bowen-Conradi syndrome 44 cases Osteodysplasty, Melnick-Needles type > 50 cases Ear-patella-short stature syndrome 42 cases Ring chromosome 20 > 50 cases Desbuquois syndrome > 40 cases Acromesomelic dysplasia, Maroteaux type 50 cases 3M syndrome 40 cases Acroosteolysis dominant type 50 cases Babesiosis 40 cases Adenylosuccinate lyase deficiency 50 cases Carpenter syndrome 40 cases Anorchidia, bilateral 50 cases Chylomicron retention disease 40 cases Ascher syndrome 50 cases Coffin-Siris syndrome 40 cases Benign paroxysmal torticollis of infancy 50 cases Ectodermal dysplasia, hypohidrotic, autosomal 40 cases dominant Cholestasis - lymphoedema 50 cases Galloway-Mowat syndrome 40 cases Encephalopathy due to sulphite oxidase deficiency 50 cases Macrocephaly - Cutis Marmorata Telangiectatica 40 cases Focal myositis 50 cases Congenita Fronto-temporal dementia and Parkinsonism linked 50 cases Methimazole embryofetopathy 40 cases to chromosome 17 (FTDP-17) Phytosterolemia 40 cases Glucocorticoid deficiency, familial 50 cases WHIM syndrome 40 cases Glucosephosphate isomerase deficiency 50 cases Acromicric dysplasia < 40 cases ICF syndrome 50 cases Arterial tortuosity < 40 cases Juvenile hyaline fibromatosis 50 cases Mucopolysaccharidosis type 7 < 40 cases Mucosulfatidosis 50 cases Progressive bulbar paralysis of childhood < 40 cases Ocular motor apraxia Cogan type 50 cases Hypotrichosis simplex 38 cases Osteopetrosis, intermediate form 50 cases Mandibuloacral dysplasia 37 cases Paget disease juvenile type 50 cases Oculocerebrocutaneous syndrome 36 cases Peters-plus syndrome 50 cases Spondyloenchondrodysplasia 36 cases Prolidase deficiency 50 cases Carnitine palmitoyl transferase 1 deficiency 35 cases Rhombencephalosynapsis 50 cases Cobb syndrome 35 cases Ring chromosome 14 50 cases Hereditary sensory and autonomic neuropathy, 35 cases Schnitzler syndrome 50 cases type 2 Succinic acidemia 50 cases Acrocallosal syndrome, Schinzel type 34 cases Triple H (HHH) syndrome 50 cases Antley-Bixler syndrome 34 cases Waardenburg-Shah syndrome 50 cases Pyogenic arthritis - pyoderma gangrenosum - acne 34 cases Aglossia adactylia < 50 cases Ring chromosome 1 34 cases Blepharo-cheilo-dontic syndrome < 50 cases Schinzel-Giedion midface retraction syndrome 34 cases Branchio-oculo-facial syndrome < 50 cases Björnstad syndrome 33 cases Cholesteryl ester storage disease < 50 cases Marshall-Smith syndrome 33 cases DOOR syndrome < 50 cases Methylcobalamin deficiency type cbl G 33 cases Ehrlichiosis < 50 cases Osteopetrosis autosomal dominant type 1 33 cases Fibular aplasia - ectrodactyly < 50 cases Polycystic ovaries - urethral sphincter dysfunction 33 cases Goldmann-Favre syndrome < 50 cases Double outlet left ventricle 32 cases Granulomatous slack skin < 50 cases Olmsted syndrome 32 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 10 Diseases name Number of Diseases name Number of published cases published cases or families or families Segmental odontomaxillary dysplasia 32 cases Symmetrical thalamic calcifications 29 cases Argininemia 31 cases Hypertrichosis cubiti - short stature 28 cases CDG syndrome type Ic > 30 cases Catel-Manzke syndrome 27 cases Non-distal trisomy 8q > 30 cases GAPO syndrome 27 cases Tricho-dento-osseous syndrome > 30 cases Geleophysic dwarfism 27 cases Agnathia holoprosencephaly situs inversus 30 cases Insomnia, familial fatal 27 cases Anophthalmia - hypothalamo-pituitary 30 cases Limb-mammary syndrome 27 cases insufficiency Methylcobalamin deficiency type cbl E 27 cases Camptodactyly - tall stature - scoliosis - hearing 30 cases 3C syndrome 25 cases loss Atelosteogenesis II 25 cases Carnitine-acylcarnitine translocase deficiency 30 cases Book syndrome 25 cases Carnosinemia 30 cases Erythrokeratodermia ataxia 25 cases Cataract cardiomyopathy 30 cases Keratoderma palmoplantar - spastic paralysis 25 cases CHILD syndrome 30 cases Opsismodysplasia 25 cases Dermopathy restrictive lethal 30 cases Plummer-Vinson syndrome 25 cases Early myoclonic encephalopathy 30 cases Wiedemann-Rautenstrauch syndrome 25 cases Elejalde syndrome 30 cases Hepatic veno-occlusive disease - immunodeficiency < 25 cases Geroderma osteodysplastica 30 cases Bartsocas-Papas syndrome 24 cases Humeroradioulnar synostosis 30 cases Distal myopathy, with early respiratory muscle 24 cases Marden-Walker syndrome 30 cases involvement Marshall’s syndrome with periodic fever 30 cases Synspondylism 24 cases Mevalonicaciduria 30 cases Congenital bronchobiliary fistula 23 cases Omodysplasia 30 cases Deletion 2q24 23 cases Ophthalmo acromelic syndrome 30 cases Johanson-Blizzard syndrome 23 cases Otopalatodigital syndrome 30 cases Phosphoglycerate kinase 1 deficiency 23 cases Scalp-ear-nipple syndrome 30 cases Potocki-Shaffer syndrome 23 cases SHORT syndrome 30 cases Treft-Sanborn-Carey syndrome 23 cases Triose phosphate-isomerase deficiency 30 cases Acro-pectoral syndrome 22 cases Weaver syndrome 30 cases Aortic dilatation- joint hypermobility- arterial 22 cases Acrofacial dysostosis, postaxial < 30 cases tortuosity Acropectorovertebral dysplasia < 30 cases Pierson syndrome 22 cases Congenital brain dysgenesis due to glutamine < 30 cases Split hand - split foot - deafness 22 cases synthetase deficiency Craniolenticulosutural dysplasia 21 cases Developmental delay due to 2-methylbutyryl-CoA < 30 cases Dehydratase deficiency 21 cases dehydrogenase deficiency Odonto-tricho-ungual-digito-palmarn syndrome 21 cases Ectodermal dysplasia - absent dermatoglyphs < 30 cases Spinocerebellar ataxia, infantile onset 21 cases Encephalopathy due to hydroxykynureninuria < 30 cases Craniodiaphyseal dysplasia > 20 cases Frontometaphyseal dysplasia < 30 cases Fumaric aciduria > 20 cases Glycogen storage disease type 7 < 30 cases Rubella panencephalitis > 20 cases Johnson neuroectodermal syndrome < 30 cases 3-methylglutaconic aciduria, type 1 20 cases Nasopalpebral lipoma - coloboma - telecanthus < 30 cases Acrorenal syndrome 20 cases Neurometabolic disorder due to serine deficiency < 30 cases Arrhinia 20 cases Obesity due to congenital leptin deficiency < 30 cases Pontocerebellar hypoplasia type 2 < 30 cases Calvarial doughnut lesions - bone fragility 20 cases Spontaneous periodic hypothermia < 30 cases CDG syndrome type Ib 20 cases Wrinkly skin syndrome < 30 cases Congenital indifference to pain 20 cases Cone rod dystrophy 29 cases Craniofrontonasal dysplasia, Teebi type 20 cases epilepsy with migrant focal crisis 29 cases Distal monosomy 8p 20 cases Mosaic variegated aneuploidy syndrome 29 cases Gray platelet syndrome 20 cases Orofaciodigital syndrome, type 6 29 cases Juvenile temporal arteritis 20 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 11 Diseases name Number of Diseases name Number of published cases published cases or families or families Lacrimo-auriculo-dento-digital syndrome 20 cases Glycogen storage, type 0 16 cases Lipoamide dehydrogenase deficiency 20 cases Mental retardation, X-linked - Dandy Walker 16 cases malformation - Basal ganglia disease - Seizures PIBIDS syndrome 20 cases Mental retardation, X-linked, South African type 16 cases Timothy syndrome 20 cases Metaphyseal chondrodysplasia, Jansen type 16 cases Acromegaloid facial appearance syndrome < 20 cases Microgastria - limb reduction defect 16 cases Acromegaloid facies - hypertrichosis < 20 cases Orbital leiomyoma 16 cases Bronchopneumopathy, chronic, due to TAP < 20 cases deficiency Orofaciodigital syndrome, type 4 16 cases Carey fineman ziter syndrome < 20 cases Ablepharon macrostomia syndrome 15 cases ‘Ectodermal dysplasia, ‘’pure’’ hair-nail type’ < 20 cases Angel-shaped phalango-epiphyseal dysplasia 15 cases Epidermolysis bullosa simplex - limb girdle < 20 cases IBIDS syndrome 15 cases muscular dystrophy Myhre syndrome 15 cases Hemorrhagic disorders due to collagen receptors < 20 cases Sensenbrenner syndrome 15 cases deficiency Umbilical cord ulceration - 15 cases Hypertrichosis, anterior cervical, isolated < 20 cases Congenital anosmia, isolated < 15 cases Ichthyosis bullosa of Siemens < 20 cases Immunodeficiency due to interleukin-1 receptor- < 15 cases IMAGe syndrome < 20 cases associated kinase-4 deficiency Interstitial granulomatous dermatitis with arthritis < 20 cases Mirhosseini-Holmes-Walton syndrome < 15 cases Keratosis palmaris et plantaris - clinodactyly < 20 cases Odonto-onycho-dermal dysplasia < 15 cases Laryngeal abductor paralysis - mental retardation < 20 cases Taurodontia - absent teeth - sparse hair < 15 cases Lipodystrophy, familial partial, Köbberling type < 20 cases Wilson-Turner syndrome > 14 cases Metaphyseal anadysplasia < 20 cases ADULT syndrome 14 cases Orotic aciduria hereditary < 20 cases Anophthalmia/microphthalmia - esophageal atresia 14 cases Perlman syndrome < 20 cases Atkin-Flaitz syndrome 14 cases Radio-ulnar synostosis - amegakaryocytic < 20 cases Beta-mannosidosis 14 cases thrombocytopaenia DEND syndrome 14 cases RAPADILINO syndrome < 20 cases Dermo-odonto dysplasia 14 cases Ring chromosome 10 < 20 cases Fingerprints absence - congenital milia 14 cases Woolly hair - palmoplantar keratoderma - dilated < 20 cases cardiomyopathy Muscular dystrophy, limb girdle, autosomal 14 cases recessive, type 2G 6q terminal deletion 19 cases Oligocone trichromacy 14 cases Amelo-cerebro-hypohidrotic syndrome 19 cases Optic atrophy and cataract, autosomal dominant 14 cases Craniosynostosis, Boston type 19 cases Ring chromosome 17 14 cases Hereditary inclusion body myopathy - joint 19 cases contractures - ophthalmoplegia Aromatase deficiency 13 cases Schopf-Schulz-Passarge syndrome 19 cases Chondrodysplasia, Blomstrand type 13 cases Crisponi syndrome 18 cases Diaphragmatic hernia - exomphalos - corpus 13 cases callosum agenesis Hypertrichotic osteochondrodysplasia 18 cases Hypotelorism - cleft palate - hypospadias 13 cases Terminal osseous dysplasia - pigmentary defects 18 cases Posterior column ataxia - retinitis pigmentosa 13 cases Aminopterin embryofetopathy 17 cases Acro-pectoro-renal field defect 12 cases Erythroderma lethal congenital 17 cases Alopecia- epilepsy - pyorrhea - mental 12 cases Folate malabsorption, hereditary 17 cases subnormality GTP cyclohydrolase I deficiency 17 cases Ataxia - deafness - optic atrophy, lethal 12 cases Hypokeratosis, palmo-plantar, circumscribed 17 cases Atelosteogenesis I 12 cases Malonic aciduria 17 cases Atelosteogenesis III 12 cases Mental retardation, X linked, with seizures, short 17 cases Atrial tachyarrhythmia with short pr interval 12 cases stature, and midface hypoplasia Wolcott-Rallison syndrome 17 cases Coloboma of macula - brachydactyly type B 12 cases Acromegaly - cutis verticis gyrata - corneal 16 cases Coloboma uveal with cleft lip palate and mental 12 cases leukoma retardation Antley-Bixler-like syndrome - ambiguous genitalia 16 cases Distal myopathy with posterior leg and anterior 12 cases - disordered steroidogenesis upper limb involvement

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 12 Diseases name Number of Diseases name Number of published cases published cases or families or families Distal myopathy with vocal cord weakness 12 cases Goldberg-Shprintzen megacolon syndrome 10 cases Dopamine beta-hydroxylase deficiency 12 cases Hyperkeratosis - hyperpigmentation syndrome 10 cases Haemolytic anaemia due to adenylate kinase 12 cases Ichthyosis follicularis - atrichia - photophobia 10 cases deficiency Iris coloboma with ptosis - intellectual deficit 10 cases Hypoparathyroidism, deafness and renal disease 12 cases Juberg hayward syndrome 10 cases (HDR) Lipodystrophy, familial partial, associated with 10 cases Mental retardation, X-linked - macrocephaly 12 cases PPARG mutations - macro-orchidism Mental retardation, X-linked - hypotonia - facial 10 cases N-acetyl-alpha-D-galactosaminidase deficiency 12 cases dysmorphism - aggressive behaviour Osteocraniostenosis 12 cases Mental retardation, X-linked, syndromic 7 10 cases Winchester disease 12 cases Muscular atrophy ataxia retinitis pigmentosa 10 cases Anonychia - onychodystrophy with hypoplasia or 11 cases diabetes mellitus absence of distal phalanges Neurodegenerative syndrome, X-linked, Hamel type 10 cases Atrial septal defect atrioventricular conduction 11 cases Nevo syndrome 10 cases Corpus callosum dysgenesis, X-linked recessive 11 cases Pollitt syndrome 10 cases Fibrochondrogenesis 11 cases Progressive vertebral fusion, non-infectious, 10 cases Fibular dimelia - diplopodia 11 cases syndromic form Foveal hypoplasia presenile cataract 11 cases Progressive vertebral fusion, non-infectious, 10 cases syndromic form Fuhrmann syndrome 11 cases Pseudodiastrophic dysplasia 10 cases Lopez-Hernandez syndrome 11 cases Renal-hepatic-pancreatic dysplasia - Dandy-Walker 10 cases Mental retardation, X-linked, Snyder type 11 cases cysts Necrotizing encephalopathy, acute, autosomal 11 cases Succinyl-CoA acetoacetate transferase deficiency 10 cases dominant Toriello-Lacassie-Droste syndrome 10 cases PELVIS syndrome 11 cases Aase-Smith syndrome < 10 cases Pterygium syndrome, antecubital 11 cases Acrofacial dysostosis Rodriguez type < 10 cases Trichomegaly retina pigmentary degeneration 11 cases dwarfism Acromelanosis < 10 cases CHAND syndrome > 10 cases Astley-Kendall dysplasia < 10 cases Chediak-Higashi syndrome > 10 cases Carpo tarsal osteochondromatosis < 10 cases Median cleft of the upper lip - corpus callosum > 10 cases Carpo tarsal osteolysis recessive < 10 cases lipoma - cutaneous polyps Cerebral gigantism - jaw cysts < 10 cases Acromesomelic dysplasia Hunter-Thompson type 10 cases Corneal dystrophy - perceptive deafness < 10 cases Albright like syndrome 10 cases Deafness - lymphoedema - leukaemia < 10 cases Ambras syndrome 10 cases Diaphanospondylodysostosis < 10 cases Arthrogryposis multiplex congenita -whistling face 10 cases Digitorenocerebral syndrome < 10 cases Athabaskan brainstem dysgenesis syndrome 10 cases Gaucher disease - ophthalmoplegia - cardiovascular < 10 cases Barber-Say syndrome 10 cases calcification Boomerang dysplasia 10 cases Glomerulonephritis sparse hair telangiectases < 10 cases Cardiac conduction disease, dilated 10 cases Greenberg dysplasia < 10 cases cardiomyopathy and brachydactyly Hypopituitarism - microphthalmia < 10 cases Cataract mental retardation hypogonadism 10 cases Myoclonus hereditary - progressive distal muscular < 10 cases Cerebro-oculo-nasal syndrome 10 cases atrophy Char syndrome 10 cases Pacman dysplasia < 10 cases Charcot-Marie-Tooth disease - nephropathy 10 cases Palmoplantar porokeratosis of Mantoux < 10 cases Choroido cerebral calcification syndrome infantile 10 cases Pancreatic hypoplasia - diabetes - heart disease < 10 cases form Pfeiffer-type cardiocranial syndrome < 10 cases Colobomatous microphthalmia heart disease 10 cases Phosphoenolpyruvate carboxykinase (PEPCK) < 10 cases hearing loss deficiency Diffuse palmoplantar keratoderma - acrocyanosis 10 cases Progeria - short stature - pigmented nevi < 10 cases Distal monosomy 5q 10 cases Pseudo-Zellweger syndrome < 10 cases Ectodermal dysplasia - skin fragility syndrome 10 cases Singleton-Merten dysplasia < 10 cases Flynn aird syndrome 10 cases XK aprosencephaly < 10 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 13 Diseases name Number of Diseases name Number of published cases published cases or families or families Ataxia - apraxia - mental retardation, X-linked 9 cases MEHMO syndrome 7 cases Atransferrinemia 9 cases MEHMO syndrome 7 cases Bosley-Salih-Alorainy syndrome 9 cases Mental retardation, X-linked, severe, Gustavson 7 cases type Brachymorphism - onychodysplasia - 9 cases dysphalangism Michels syndrome 7 cases Cardiomyopathy - cataract - hip spine disease 9 cases Mitochondrial myopathy with sideroblastic anaemia 7 cases Gamma-glutamylcysteine synthetase deficiency 9 cases Multiple fibrofolliculoma familial 7 cases Guanidinoacetate methyltransferase deficiency 9 cases Neurodegenerative syndrome, X-linked, Bertini type 7 cases Macrostomia - preauricular tags - external 9 cases Neutropenia, severe congenital, X-linked 7 cases ophthalmoplegia Obesity due to pro-opiomelanocortin deficiency 7 cases Mental retardation, X-linked, Shashi type 9 cases Retinal degeneration nanophthalmos glaucoma 7 cases Methylmalonicaciduria - homocystinuria, type cbl F 9 cases Retinohepatoendocrinologic syndrome 7 cases Microdontia - type I microtia - deafness 9 cases Stern-Lubinsky-Durrie syndrome 7 cases Oculocerebrofacial syndrome, Kaufman type 9 cases Torticollis keloids cryptorchidism renal dysplasia 7 cases Tricho-retino-dento-digital syndrome 9 cases 3-hydroxy 3-methylglutaryl-CoA (HMG) synthase 6 cases 5-oxoprolinase deficiency 8 cases Acrofacial dysostosis catania form 6 cases Ackerman syndrome 8 cases Agonadism - dextrocardia - diaphragmatic hernia 6 cases Ankylosing vertebral hyperostosis with tylosis 8 cases Aplasia cutis congenita of limbs recessive 6 cases Ataxia-deafness-retardation syndrome 8 cases Biliary tract malformation - renal failure 6 cases Campomelia Cumming type 8 cases Blepharophimosis - ptosis - esotropia - syndactyly 6 cases Camptodactyly syndrome guadalajara type 1 8 cases - short stature COACH syndrome 8 cases CDG syndrome type Ig 6 cases Corpus callosum, agenesis - cataract - 8 cases Cutis gyrata acanthosis nigricans craniosynostosis 6 cases immunodeficiency Deafness, enamel hypoplasia, nail defects 6 cases Deafness skeletal dysplasia lip granuloma 8 cases Eiken syndrome 6 cases Familial hematuria, autosomal dominant - retinal 8 cases Epilepsy telangiectasia 6 cases arteriolar tortuosity - contractures Fanconi ichthyosis dysmorphism 6 cases Hydrocephalus - costovertebral dysplasia - 8 cases Sprengel anomaly Grange syndrome 6 cases Hypomyelination - congenital cataract 8 cases Hidrotic ectodermal dysplasia type Christianson- 6 cases Fourie Kallmann syndrome - heart disease 8 cases Hypopituitarism - postaxial polydactyly 6 cases Mental retardation, X-linked - dysmorphism - 8 cases cerebral atrophy Isotretinoin-like syndrome 6 cases Mental retardation, X-linked, Abidi type 8 cases Keratosis follicularis - dwarfism - cerebral atrophy 6 cases Mental retardation, X-linked, Vitale type 8 cases Megalencephaly - polymicrogyria - post-axial 6 cases polydactyly - hydrocephalus Micro syndrome 8 cases Mental retardation sparse hair brachydactyly 6 cases Pancreas agenesis 8 cases Mental retardation X-linked - psychosis - 6 cases Spondylometaphyseal dysplasia - cone-rod 8 cases macroorchidism dystrophy Mental retardation, X-linked, Armfield type 6 cases Acro-renal-mandibular syndrome 7 cases Mental retardation, X-linked, Zorick type 6 cases Albinism ocular - late onset sensorineural deafness 7 cases Moore-Federman syndrome 6 cases Branchial arch syndrome, X-linked 7 cases Polysyndactyly - cardiac malformation 6 cases Cardiogenital syndrome 7 cases Serpentine fibula polycystic kidneys 6 cases CDG syndrome type Ie 7 cases Spasticity - mental retardation - epilepsy, X-linked 6 cases CEDNIK syndrome 7 cases Symphalangism with multiple anomalies of hands 6 cases Cleft palate lateral synechia syndrome 7 cases and feet Dihydropyrimidinuria 7 cases Thumb stiffness - brachydactyly - mental 6 cases Ehlers-Danlos syndrome type 7C 7 cases retardation Gamma-glutamyl transpeptidase deficiency 7 cases W syndrome 6 cases Genitopatellar syndrome 7 cases Wieacker-Wolff syndrome 6 cases Lenz-Majewski hyperostotic dwarfism 7 cases Zunich-Kaye syndrome 6 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 14 Diseases name Number of Diseases name Number of published cases published cases or families or families Achalasia - microcephaly 5 cases Oculo-palato-cerebral syndrome 5 cases Acro-fronto-facio-nasal dysostosis 5 cases Odontomicronychial dysplasia 5 cases Adducted thumbs-arthrogryposis, Dundar type 5 cases Onycho-tricho-dysplasia - neutropenia 5 cases Alopecia - contractures - dwarfism - mental 5 cases P2Y12, deficiency of 5 cases retardation Palmoplantar keratoderma - XX sex reversal - 5 cases Anonychia microcephaly 5 cases predisposition to squamous cell carcinoma Arachnodactyly ossification abnormal mental 5 cases Paraplegia - brachydactyly - cone-shaped epiphysis 5 cases retardation Sacral hemangiomas - multiple congenital 5 cases Aurocephalosyndactyly 5 cases abnormalities Bamforth syndrome 5 cases Sillence syndrome 5 cases Beta-ureidopropionase deficiency 5 cases Spinocerebellar ataxia X-linked, type 3 5 cases Bradyopsia 5 cases Cystic hamartoma of lung and kidney < 5 cases Branchiogenic deafness syndrome 5 cases Lathosterolosis < 5 cases CAMOS syndrome 5 cases Sakati-Nyhan syndrome < 5 cases CDG syndrome type Id 5 cases Abruzzo-Erickson syndrome 4 cases CDG syndrome type Ih 5 cases Acrofacial dysostosis, palagonia type 4 cases Choanal atresia - deafness - cardiac defects 5 cases Anophthalmia plus syndrome 4 cases - dysmorphism Aortic arch anomaly peculiar facies mental 4 cases Cleft palate - cardiac defect - genital anomalies 5 cases retardation - ectrodactyly Aplasia cutis - myopia 4 cases Craniodigital syndrome - intellectual deficit 5 cases Arhinia choanal atresia microphthalmia 4 cases Craniosynostosis - dysmorphism - brachydactyly 5 cases Arterial dissection - lentiginosis 4 cases Curry-Jones syndrome 5 cases Benign exophthalmos syndrome 4 cases Dacryocystitis osteopoikilosis 5 cases Bone dysplasia lethal holmgren type 4 cases Depigmentation of the iris, acute, bilateral 5 cases Bone fragility, craniosynostosis, proptosis, 4 cases Dermatoosteolysis Kirghizian type 5 cases hydrocephalus Ectrodactyly - ectodermal dysplasia without 5 cases Bonnemann-Meinecke-Reich syndrome 4 cases clefting Brachydactyly long thumb type 4 cases Fine-Lubinsky syndrome 5 cases Caudal dysgenesis familial type 4 cases German syndrome 5 cases CDG syndrome type If 4 cases Glaucoma - sleep apnoea 5 cases CDG syndrome type IIa 4 cases Humerospinal dysostosis 5 cases CDG syndrome type Ik 4 cases Humeroulnar synostosis 5 cases Cholestasis pigmentary retinopathy cleft palate 4 cases Hypothyroidism - dysmorphism - postaxial 5 cases Chondrodysplasia lethal recessive 4 cases polydactyly - intellectual deficit Choroideremia deafness obesity 4 cases Ichthyosis - male hypogonadism 5 cases Cleft lip and palate malrotation cardiopathy 4 cases Lissencephaly type III - familial foetal akinesia 5 cases sequence Coxoauricular syndrome 4 cases Lymphoedema - cerebral arteriovenous anomaly 5 cases Cranio osteoarthropathy 4 cases Matthew-Wood syndrome 5 cases Craniofaciocardioskeletal syndrome 4 cases Mental retardation, X-linked - choreoathetosis 5 cases Craniosynostosis dandy walker hydrocephalus 4 cases - abnormal behaviour Deafness - peripheral neuropathy - arterial disease 4 cases Mental retardation, X-linked - 5 cases Diabetes mellitus, permanent neonatal - pancreatic 4 cases - dysmorphism and cerebellar agenesis Mental retardation, X-linked, Lubs type 5 cases Diaphragmatic defect - limb deficiency - skull 4 cases defect Methylmalonicacidemia - homocystinuria, type 5 cases cbl D Duker-Weiss-Siber syndrome 4 cases Neonatal death immune deficiency 5 cases Ectodermal dysplasia berlin type 4 cases Nephropathy - deafness - hyperparathyroidism 5 cases Ectopia lentis chorioretinal dystrophy myopia 4 cases Nephrosis deafness urinary tract digital 5 cases Facial onset sensory and motor neuronopathy 4 cases malformations Gombo syndrome 4 cases Oculodentoosseous dysplasia recessive 5 cases Gorlin-Chaudhry-Moss, syndrome 4 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 15 Diseases name Number of Diseases name Number of published cases published cases or families or families Growth delay - intellectual deficit - 4 cases Odontotrichomelic syndrome 4 cases mandibulofacial dysostosis - microcephaly - cleft Orofaciodigital syndrome, type 5 4 cases palate Osteopoikilosis - short stature - intellectual deficit 4 cases Growth delay due to insulin-like growth factor I 4 cases deficiency Palmoplantar keratoderma - amyotrophy 4 cases Growth retardation - microcephaly - digital 4 cases Paraplegia - mental retardation - hyperkeratosis 4 cases abnormalities - hypospadias Recurrent infections - short stature - 4 cases Hidrotic ectodermal dysplasia Halal type 4 cases hypopigmentation - coarse face Homocarnosinosis 4 cases Rolled and spiral hairs - palmoplantar keratoderma 4 cases Hypogammaglobulinemia due to CD19 deficiency 4 cases Severe achondroplasia - developmental delay 4 cases - acanthosis nigricans Hypomandibular faciocranial dysostosis 4 cases Short stature - webbed neck - heart disease 4 cases Hypomyelination - hypogonadotropic 4 cases hypogonadism - hypodontia Simpson-Golabi-Behmel syndrome, type 2 4 cases Hypomyelination - hypogonadotropic 4 cases Sparse hair - short stature - skin anomalies 4 cases hypogonadism - hypodontia Spastic paraplegia - nephritis - deafness 4 cases Hypotrichosis - lymphoedema - telangiectasia 4 cases Spondylometaphyseal dysplasia with combined 4 cases Ichthyosis alopecia eclabion ectropion mental 4 cases immunodeficiency retardation Tricho-odonto-onychial dysplasia 4 cases Immunodeficiency with natural-killer cell 4 cases Acromesomelic dysplasia brahimi bacha type 3 cases deficiency Agammaglobulinemia - microcephaly - 3 cases Leukodystrophy with oligodontia 4 cases craniosynostosis - severe dermatitis Leukoencephalopathy - metaphyseal 4 cases Amelia, autosomal recessive 3 cases chondrodysplasia Aniridia absent patella 3 cases Leukoencephalopathy - palmoplantar keratoderma 4 cases Aniridia ptosis mental retardation obesity familial 3 cases Liver disease - retinitis pigmentosa - 4 cases type polyneuropathy - epilepsy Anonychia with flexural pigmentation 3 cases Macrogyria pseudobulbar palsy 4 cases Anophthalmia - megalocornea - cardiopathy 3 cases Malignant hyperthermia - arthrogryposis - 4 cases - skeletal anomalies torticollis Aphalangy - hemivertebrae - urogenital-intestinal 3 cases Mental retardation - dysmorphism - hypogonadism 4 cases dysgenesis - diabetes mellitus Aplasia cutis congenita - intestinal 3 cases Mental retardation, X-linked - hypogonadism 4 cases lymphangiectasia - ichthyosis - obesity - short stature Arachnodactyly - mental retardation - dysmorphism 3 cases Mental retardation, X-linked - seizures - psoriasis 4 cases AREDYLD syndrome 3 cases Mental retardation, X-linked, Miles-Carpenter type 4 cases Axenfeld-Rieger anomaly - hydrocephaly - skeletal 3 cases Mental retardation, X-linked, Schimke type 4 cases abnormalities Mental retardation, X-linked, Seemanova type 4 cases Blepharoptosis - myopia - ectopia lentis 3 cases Mental retardation, X-linked, Siderius type 4 cases Branchio-skeleto-genital syndrome 3 cases Mental retardation, X-linked, Stevenson type 4 cases Buttiens-Fryns syndrome 3 cases Mental retardation, X-linked, Stocco Dos Santos 4 cases Camptodactyly - fibrous tissue hyperplasia - 3 cases type skeletal dysplasia Mental retardation, X-linked, Stoll type 4 cases Cataract deafness hypogonadism 3 cases Metaphyseal acroscyphodysplasia 4 cases Cervical hypertrichosis - peripheral neuropathy 3 cases Microcephalic osteodysplastic dysplasia, Saul- 4 cases Cortical blindness - mental retardation - 3 cases Wilson type polydactyly Microcephaly micropenis convulsions 4 cases Cranio fronto nasal dysplasia poland anomaly 3 cases Multiple pterygium syndrome, autosomal dominant 4 cases Craniofacial dysmorphism - coloboma - corpus 3 cases Myoclonus cerebellar ataxia deafness 4 cases callosum agenesis Myopathy due to calsequestrin and SERCA1 protein 4 cases Craniofacial-deafness-hand syndrome 3 cases overload Craniosynostosis - intracranial calcifications 3 cases Neurodegeneration due to 3-hydroxyisobutyryl-CoA 4 cases Cutaneous albinism, ermine phenotype 3 cases hydrolase deficiency Cutaneous photosensitivity colitis lethal 3 cases Neuroectodermal endocrine syndrome 4 cases Deafness - opticoacoustic nerve atrophy - 3 cases Oculo-oto-facial dysplasia 4 cases dementia

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 16 Diseases name Number of Diseases name Number of published cases published cases or families or families Deafness-mental retardation, Martin-Probst type 3 cases Omphalocele cleft palate syndrome lethal 3 cases Deafness-mental retardation, Martin-Probst type 3 cases Orofaciodigital syndrome, type 3 3 cases Disorder of sex development - mental retardation 3 cases Osteogenesis imperfecta, congenital - 3 cases microcephaly - cataracts Ectodermal dysplasia, hypohidrotic - 3 cases hypothyroidism - ciliary dyskinesia Osteoporosis oculocutaneous hypopigmentation 3 cases syndrome Ectodermic dysplasia hypothyroidism cleft 3 cases Osteosclerosis - ichthyosis - premature ovarian 3 cases Eyebrow duplication syndactyly 3 cases failure Facial dysmorphism macrocephaly myopia dandy 3 cases Psychomotor retardation due to S- 3 cases walker adenosylhomocysteine hydrolase deficiency Faciocardiomelic dysplasia lethal 3 cases Qazi-Markouizos syndrome 3 cases Gardner-Morrison-Abbott syndrome 3 cases Rambaud galian syndrome 3 cases Glaucoma - ectopia - microspherophakia - stiff 3 cases Seizures - intellectual deficit due to 3 cases joints - short stature hydroxylysinuria Global developmental delay - osteopenia - 3 cases Sensorineural hearing loss, early greying, and 3 cases ectodermal defect essential tremor Goodman syndrome 3 cases Short stature mental retardation eye anomalies 3 cases Haemolytic anaemia due to glutathione reductase 3 cases cleft lip palate deficiency Split hand urinary anomalies 3 cases Hair defect photosensitivity mental retardation 3 cases Summitt syndrome 3 cases Hirschsprung disease - nail hypoplasia - 3 cases Thumb absent short stature immune deficiency 3 cases dysmorphism Thymic renal anal lung dysplasia 3 cases Hypogonadism - retinitis pigmentosa 3 cases Trigonocephaly - short stature - developmental 3 cases Lewis-Pashayan syndrome 3 cases delay Lipodystrophy - mental retardation - deafness 3 cases Ulbright hodes syndrome 3 cases Lumbosacral vertebrae, posterior fusion of - 3 cases 46,XX disorders of sex development - skeletal 2 cases blepharoptosis anomalies Lymphoedema - atrial septal defects - facial 3 cases Acrocraniofacial dysostosis 2 cases changes Acrofacial dysostosis autosomal recessive 2 cases Malabsorptive diarrhea due to paucity of 3 cases enteroendocrine cells, congenital Agenesis of the corpus callosum - mental 2 cases retardation - coloboma - micrognathia Mental retardation - hypoplastic corpus callosum 3 cases - preauricular tag Alar cartilages hypoplasia - coloboma - telecanthus 2 cases Mental retardation, X linked - precocious puberty 3 cases Alopecia - hypogonadism - extrapyramidal disorder 2 cases - obesity Amaurosis - hypertrichosis 2 cases Mental retardation, X-linked - 3 cases Aniridia renal agenesis psychomotor retardation 2 cases hypogammaglobulinemia - progressive neurological deterioration Aniridia-mental retardation syndrome 2 cases Mental retardation, X-linked, Shrimpton type 3 cases Arthrogryposis - hyperkeratosis, lethal form 2 cases Mental retardation, X-linked, Wilson type 3 cases Atherosclerosis- deafness - diabetes - epilepsy 2 cases - nephropathy Mental retardation, X-linked, Wittwer type 3 cases Aughton syndrome 2 cases Microcephaly - cleft palate 3 cases Auricular abnormalities - cleft lip with or without 2 cases Microcephaly cardiomyopathy 3 cases cleft palate - ocular abnormalities Microcytic anaemia - liver iron overload - low 3 cases Auriculoocular anomalies - cleft lip 2 cases ferritinemia Bangstad syndrome 2 cases Microphthalmia - brain atrophy 3 cases Beemer-Ertbruggen syndrome 2 cases Mitral regurgitation - deafness - skeletal anomalies 3 cases Blepharo-facio-skeletal syndrome 2 cases Mullerian derivatives - lymphangiectasia - 3 cases polydactyly Bouwes Bavinck syndrome 2 cases N syndrome 3 cases Brachytelephalangy - dysmorphism - Kallmann 2 cases Nail patella-like - renal disease 3 cases syndrome Nanism due to growth hormone qualitative 3 cases Braddock syndrome 2 cases anomaly Brain malformation - congenital heart disease 2 cases Neuroaxonal dystrophy 3 cases - postaxial polydactyly Oculo-osteo-cutaneous syndrome 3 cases Camptodactyly syndrome, Guadalajara type 2 2 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 17 Diseases name Number of Diseases name Number of published cases published cases or families or families Cardiomyopathy - renal anomalies 2 cases Epilepsy microcephaly skeletal dysplasia 2 cases Cataract - microphthalmia - septal defect 2 cases Fuqua-Berkovitz syndrome 2 cases Cataract - nephropathy - encephalopathy 2 cases Gamma aminobutyric acid transaminase deficiency 2 cases Cataract- ataxia - deafness 2 cases Gonadal dysgenesis, XY type - associated 2 cases anomalies CDG syndrome type IIe 2 cases Heart defects - limb shortening 2 cases CDG syndrome type IL 2 cases Hec syndrome 2 cases CDG syndrome, type IIh 2 cases Hemolytic anaemia, lethal - genital anomalies 2 cases Chondrodysplasia - disorder of sex development 2 cases Hennekam-Beemer syndrome 2 cases Choroidal atrophy alopecia 2 cases Hersh-Podruch-Weisskopf syndrome 2 cases Cleft lip palate - mental retardation - corneal 2 cases opacities Hirschsprung disease - deafness - polydactyly 2 cases Cleft lip retinopathy 2 cases Hydrocephaly tall stature joint laxity 2 cases Cleft palate short stature vertebral anomalies 2 cases Hypercoagulability syndrome, due to 2 cases glycosylphosphatidylinositol deficiency Cleft palate stapes fixation oligodontia 2 cases Hypomagnesemia with normocalciuria 2 cases Cleido rhizomelic syndrome 2 cases Hypotrichosis-mental retardation lopes type 2 cases Congenital ichthyosis microcephalus quadriplegia 2 cases Ichthyosis - hepatosplenomegaly - cerebellar 2 cases Contractures ectodermal dysplasia cleft lip palate 2 cases degeneration Cooper-Jabs syndrome 2 cases Ichthyosis - oral and digital anomalies 2 cases Corneal anesthesia deafness mental retardation 2 cases Ichthyosis congenita biliary atresia 2 cases Corneal-cerebellar syndrome 2 cases Inappropriate antidiuretic hormone secretion 2 cases Craniosynostosis fibular aplasia 2 cases syndrome Craniosynostosis radial aplasia type imaizumi 2 cases Intellectual deficit, severe - epilepsy - anal 2 cases Craniotubular syndrome 2 cases anomalies - distal phalangeal hypoplasia Cryptomicrotia - brachydactyly - excess fingertip 2 cases Iris dysplasia - hypertelorism - deafness 2 cases arch Kaler garrity stern syndrome 2 cases Cystic hygroma lethal - cleft palate 2 cases Kapur-Toriello syndrome 2 cases Dahlberg-Borer-Newcomer syndrome 2 cases Keratoderma hypotrichosis leukonychia 2 cases Dandy walker macrocephaly 2 cases Kniest-like dysplasia, lethal 2 cases Dandy walker malformation postaxial polydactyly 2 cases Kudo tamura fuse syndrome 2 cases Deaf blind hypopigmentation 2 cases Lichstenstein syndrome 2 cases Deafness - genital anomalies - metacarpal and 2 cases Lissencephaly type III - metacarpal bone dysplasia 2 cases metatarsal synostosis - dwarfism - 2 cases Deafness - vitiligo - achalasia 2 cases dysgammaglobulinemia Deafness-tubular acidosis-anaemia 2 cases Macrocephaly - immune deficiency - 2 cases Dentinogenesis imperfecta - short stature - hearing 2 cases Macrocephaly - short stature - paraplegia 2 cases loss - mental retardation Mental retardation, X-linked - acromegaly - 2 cases Dermato-cardio-skeletal syndrome Borrone type 2 cases hyperactivity Dermatoleukodystrophy 2 cases Mental retardation, X-linked - epilepsy - 2 cases Desmosterolosis 2 cases progressive joint contractures - dysmorphism Developmental malformations - deafness - dystonia 2 cases Mental retardation, X-linked - plagiocephaly 2 cases Diabetes, neonatal - congenital hypothyroidism - 2 cases Mental retardation, X-linked, Cantagrel type 2 cases congenital glaucoma - hepatic fibrosis - polycystic Mental retardation, X-linked, Reish type 2 cases kidneys Mesomelic dysplasia skin dimples 2 cases Dincsoy-Salih-Patel syndrome 2 cases Methylmalonic aciduria - microcephaly - cataract 2 cases Duane anomaly - myopathy - scoliosis 2 cases Microbrachycephaly - ptosis - cleft lip 2 cases Dysmorphism - short stature - deafness - 2 cases pseudohermaphroditism Microcephaly - glomerulonephritis - marfanoid 2 cases Ectodermal dysplasia - anhidrotic, with 2 cases habitus immunodeficiency - osteopetrosis - lymphoedema Microcephaly - seizures - mental retardation 2 cases Ectodermal dysplasia - blindness 2 cases - heart disease Eng strom syndrome 2 cases Microlissencephaly - micromelia 2 cases

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 18 Diseases name Number of Diseases name Number of published cases published cases or families or families Mitochondrial encephalomyopathy 2 cases 46 epibulbar dermoid 1 case aminoacidopathy Acrofacial dysostosis postaxial, atypical 1 case Monosomy 9q22.3 2 cases Acrofacial dysostosis, Preis type 1 case Multiple sclerosis - ichthyosis - factor 8 deficiency 2 cases Anophthalmia - short stature - obesity 1 case Nephronophtisis familial, adult form - spastic 2 cases Blaichman syndrome 1 case quadriparesia Bone dysplasia azouz type 1 case Neurodegeneration due to 3-hydroxyisobutyryl-CoA 2 cases hydrolase deficiency Bone dysplasia corpus callosum agenesis 1 case Obesity - colitis - hypothyroidism - cardiac 2 cases Cataract - hypertrichosis - intellectual deficit 1 case hypertrophy - developmental delay CDG syndrome type Ii 1 case Obesity due to prohormone convertase-I deficiency 2 cases CDG syndrome type IIb 1 case Oculo-tricho-dysplasia 2 cases CDG syndrome type IId 1 case Okamoto syndrome 2 cases CDG syndrome type Ij 1 case Ossification anomalies - psychomotor development 2 cases Chondrodysplasia situs inversus imperforate anus 1 case delay polydactyly Osteochondrodysplatic nanism - deafness - retinitis 2 cases Corneal dystrophy ichthyosis microcephaly mental 1 case pigmentosa retardation Osteogenesis imperfecta - retinopathy - seizures 2 cases Ectodermal dysplasia alopecia preaxial polydactyly 1 case - intellectual deficit Ectodermal dysplasia arthrogryposis diabetes 1 case PARC syndrome 2 cases mellitus Pilodental dysplasia with refractive errors 2 cases Ectodermal dysplasia mental retardation syndactyly 1 case Progressive neurodegeneration - joint laxity 2 cases Hyaluronidase deficiency 1 case - cataract Hypothyroidism - dermoid cyst - cleft palate 1 case Pseudoprogeria syndrome 2 cases Lissencephaly - immunodeficiency 1 case Pterygium colli - intellectual deficit - digital 2 cases anomalies Martinez monasterio pinheiro syndrome 1 case Ptosis - strabismus - rectus abdominis diastasis 2 cases Nasopharyngeal teratoma dandy walker 1 case diaphragmatic hernia Robinow-like syndrome 2 cases Nevus of ota retinitis pigmentosa 1 case Rudiger syndrome 2 cases Odonto-onycho-hypohidrotic dysplasia, midline 1 case Say barber miller syndrome 2 cases scalp defects Scalp defects - postaxial polydactyly 2 cases Orofaciodigital syndrome, type 10 1 case SCARF syndrome 2 cases Pancreatic lipomatosis duodenal stenosis 1 case Short stature brussels type 2 cases Preauricular pits renal disease 1 case Siegler brewer carey syndrome 2 cases Stoll alembik finck syndrome 1 case Small vessel disease of the brain, not NOTCH3- 2 cases Tricho oculo dermo vertebral syndrome 1 case related Tricho onycho hypohidrotic dysplasia 1 case Spastic quadriplegia retinitis pigmentosa mental 2 cases retardation Li-Fraumeni syndrome 400 families Spinal muscular atrophy - Dandy-Walker complex 2 cases Birt-Hogg-Dube syndrome > 60 families - cataracts Nance-Horan syndrome 50 families Stimmler syndrome 2 cases Muscular dystrophy, limb girdle, autosomal > 40 families Talo-patello-scaphoid osteolysis 2 cases recessive, type 2I Thyrocerebrorenal syndrome 2 cases Granulomatous arthritis of childhood 40 families Trigonocephaly - bifid nose - acral anomalies 2 cases Erythermalgia, primary 30 families Trigonocephaly - broad thumbs 2 cases LCAT deficiency 30 families Tubular renal disease - cardiomyopathy 2 cases Thiamine-responsive megaloblastic anaemia 30 families syndrome Visceral neuropathy - brain anomalies - facial 2 cases dysmorphism - developmental delay Pericarditis arthropathy camptodactyly syndrome < 30 families Weaver-Williams syndrome 2 cases Phosphoribosylpyrophosphate synthetase < 30 families superactivity Xeroderma talipes enamel defects 2 cases Neuropathy, giant axonal 20 families Zellweger-like syndrome, without peroxisomal 2 cases anomalies Overhydrated hereditary stomatocytosis 20 families 2,4-dienoyl-CoA reductase deficiency 1 case Synostoses, multiple 20 families

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 19 Diseases name Number of Diseases name Number of published cases published cases or families or families Acro-renal-ocular syndrome < 20 families Adducted thumbs - arthrogryposis, Christian type 3 families Fahr syndrome < 20 families CAMFAK syndrome 3 families Familial platelet syndrome with predisposition to < 20 families Cataract-glaucoma 3 families acute myelogenous leukaemia Cerebellar ataxia, autosomal recessive - blindness 3 families Haemolytic anaemia, nonspherocytic, due to 17 families - deafness hexokinase deficiency Cerebroretinal vasculopathy 3 families Ichthyosis prematurity syndrome 16 families Deafness-infertility syndrome 3 families Myopathy, X-linked, with excessive autophagy 15 families HERNS syndrome 3 families Familial platelet syndrome with predisposition to 13 families Hypomagnesemia with hypocalciuria 3 families acute myelogenous leukaemia Mental retardation, X-linked, with isolated growth 3 families Marie Unna congenital hypotrichosis 12 families hormone deficiency Aniridia - cerebellar ataxia - mental deficiency > 10 families Mixed dystonias 3 families Brachydactyly - arterial hypertension > 10 families Rapid-onset dystonia-parkinsonism 3 families syndrome, Loeys-Dietz type 10 families Angioma serpiginosum, familial 2 families Renpenning syndrome 10 families Ankyloblepharon filiforme - imperforate anus 2 families Acheiropodia < 10 families Auriculoosteodysplasia 2 families Angioma neurocutaneous, hereditary < 10 families Bencze syndrome 2 families Focal facial dermal dysplasia < 10 families Blepharonasofacial malformation syndrome 2 families Hypoparathyroidism familial isolated < 10 families Bullous dystrophy, macular type 2 families Keratoderma palmoplantar - deafness < 10 families Cerebellar ataxia - areflexia - pes cavus - optic 2 families Keratosis palmoplantaris - esophageal carcinoma < 10 families atrophy - sensorineural hearing loss Mental retardation, X-linked, syndromic, due to < 10 families Chorioretinal atrophy, progressive bifocal 2 families JARID1C Earlobes, thickened - conductive deafness 2 families Schinzel syndrome < 10 families Ehlers-Danlos syndrome, type 5 2 families Sebastian syndrome < 10 families Episodic ataxia, type 4 2 families VACTERL with hydrocephalus < 10 families Fibromatosis, gingival - progressive deafness 2 families Otodental syndrome 9 families Growth deficiency - brachydactyly - dysmorphism 2 families Ankyloblepharon - ectodermal defects - cleft lip 8 families Hypoparathyroidism X-linked 2 families palate Jackson-Weiss syndrome 2 families Cataract-microcornea syndrome 8 families North Carolina macular dystrophy 2 families Lethal osteosclerotic bone dysplasia 8 families Orofaciodigital syndrome, type 8 2 families EEM syndrome 7 families Partington syndrome 2 families Immune dysregulation - polyendocrinopathy 7 families - enteropathy, X linked Retinitis pigmentosa - intellectual deficit - 2 families deafness - hypogenitalism Juvenile , hypotrichosis 7 families Skeletal dysplasia - intellectual deficit 2 families Cystoid macular dystrophy 6 families Spastic paraplegia - glaucoma - intellectual deficit 2 families Developmental dysphasia familial 6 families Albinism-deafness syndrome 1 family Pontocerebellar hypoplasia type 1 6 families Alopecia - congenita keratosis palmoplantaris 1 family Encephalopathy with neuroserpin inclusion bodies, > 5 families familial form Aphalangia - syndactyly - microcephaly 1 family Anaemia, sideroblastic, X-linked - ataxia 5 families Arthrogryposis-like hand anomaly - sensorineural 1 family deafness Muscular dystrophy, limb-girdle, autosomal 5 families dominant, type 1D Banki syndrome 1 family Muscular dystrophy, limb-girdle, autosomal 5 families Camptobrachydactyly 1 family dominant, type 1E Cerebellar ataxia, autosomal recessive - saccadic 1 family Tetraamelia - pulmonary hypoplasia 5 families intrusion Symphalangism distal < 5 families Coronary artery disease - hyperlipidemia - 1 family Trichodental syndrome < 5 families hypertension - diabetes - osteoporosis Camptodactyly - taurinuria 4 families Costocoracoid ligament congenitally short 1 family IVIC syndrome 4 families Craniofacial conodysplasia 1 family Paroxysmal extreme pain disorder 4 families Craniosynostosis, Philadelphia type 1 family Triphalangeal thumbs - brachyectrodactyly 4 families Cyprus facial neuromusculoskeletal syndrome 1 family

Orphanet Reports Series - Prevalence of rare diseases: A bibliographic survey. February 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 20 Diseases name Number of Diseases name Number of published cases published cases or families or families Dyschondrosteosis - nephritis 1 family Muscular dystrophy, limb-girdle, autosomal 1 family dominant, type 1F Ehlers-Danlos syndrome type 10 1 family Muscular dystrophy, limb-girdle, autosomal 1 family Episodic ataxia, type 3 1 family dominant, type 1G Fried syndrome 1 family Oculodental syndrome Rutherfurd type 1 family Hereditary vascular retinopathy 1 family Oculogastrointestinal muscular dystrophy 1 family

Hereditary vascular retinopathy 1 family Pili torti - onychodysplasia 1 family Hydrocephalus - blue sclerae - nephropathy 1 family Ptosis - strabismus - ectopic pupils 1 family Insulin resistance, short fifth metacarpals 1 family Schizophrenia - mental retardation - deafness 1 family - retinitis Lipodystrophy, familial partial, due to AKT2 1 family mutations Short stature - pituitary and cerebellar defects 1 family - small sella turcica Mental retardation - progressive spasticity, X- 1 family linked Steroid dehydrogenase deficiency - dental 1 family anomalies Mental retardation, X-linked - Spastic paraplegia 1 family with iron deposits Tietz syndrome 1 family Mental retardation, X-linked recessive - 1 family Trichodysplasia - amelogenesis imperfecta 1 family macrocephaly - ciliary dysfunction Ulnar / fibula ray defect - brachydactyly 1 family Mental retardation, X-linked, Cabezas type 1 family Upington disease 1 family Mental retardation, X-linked, Pai type 1 family Van den Bosch syndrome 1 family Muscular dystrophy, limb-girdle, autosomal 1 family Woolly hair - hypotrichosis - everted lower lip 1 family dominant, type 1A - outstanding ears

Orphanet Reports Series - Prevalence of rare diseases: Bibliographic data. May 2008 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf 21