APPENDIX 2

APPENDIX 2 ______

INTERNATIONAL NOMENCLATURE OF CONSTITUTIONAL DISORDERS OF BONE OSTEOCHONDRODYSPLASIAS SOURCE: http://www.csmc.edu/genetics/skeletdys/ (Version December 2002)

Mode OMIM Pre- Chrom- Gene Protein OMIM of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth 1. Achondroplasia group Thanatophoric dysplasia, AD 187600 + 4p16.3 FGFR3 FGFR3 134934 Type I Thanatophoric dysplasia, AD 187610 + 4p16.3 FGFR3 FGFR3 134934 Type II Achondroplasia AD 100800 + 4p16.3 FGFR3 FGFR3 134934 Hypochondroplasia AD 146000 – 4p16.3 FGFR3 FGFR3 134934 Other FGFR3 disorders

2. Spondylodysplastic and other perinatally lethal groups Lethal platyspondylic SP 270230 + skeletal dysplasias (San Diego type, Torrance 151210 + type, Luton type) Achondrogenesis type 1A AR 200600 +

3. Metatropic dysplasia group Fibrochondrogenesis AR 228520 + Schneckenbecken AR 269250 + dysplasia Metatropic dysplasia AD 156530 + (various forms)

4. Short- dysplasia (SRP) (with or without ) group SRP type I, Saldino- AR 263530 + Noonan SRP type II, Majewski AR 263520 + SRP type III, Verma- AR 263510 + Naumoff SRP type IV, Beemer- AR 269860 + Langer Asphyxiating thoracic AR 208500 + dysplasia (Jeune) Chondroectodermal AR 225500 + 4p16 Dyplasia (Ellis-van Creveld dysplasia)

5. Atelosteogenesis-omodysplasia group Atelosteogenesis type I SP 108720 + (includes ‘Boomerang dysplasia’)

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth Omodysplasia I AD 164745 + (Maroteaux) Omodysplasia II AR 258315 + (Borochowitz) Otopalatodigital XLR 304120 + syndrome type II Atelosteogenesis Type III SP 108721 + de la Chapelle dysplasia AR 256050 +

6. Diastrophic dysplasia group Diastrophic dysplasia AR 222600 + 5q32- DTDST Sul. q33 Transporter Achondrogenesis 1B AR 600972 + 5q32- DTDST Sul. q33 Transporter Atelosteogenesis type II AR 256050 + 5q32- DTDST Sul. q33 Transporter

7. Dyssegmental dysplasia group Dyssegmental dysplasia, AR 224410 + Silverman-Handmaker type Dyssegmental dysplasia, AR 224400 + Rolland-Desbuquois type

8. Type II collagenopathies Achondrogenesis II AD 200610 + COL2A1 Type II 120140 (Langer-Saldino) 12q13.1 collagen -q13.3 Hypochondrogenesis AD 200610 + COL2A1 Type II 120140 12q13.1 collagen -q13.3 Kniest dysplasia AD 156550 + COL2A1 Type II 120140 12q13.1 collagen -q13.3 Spondyloepiphyseal AD 183900 + COL2A1 Type II 120140 dysplasia (SED) 12q13.1 collagen congenital -q13.3 Spondyloepimetaphyseal AD 184250 + COL2A1 Type II 120140 dysplasia (SEMD) 12q13.1 collagen Strudwick type -q13.3 SED with AD COL2A1 Type II 120140 12q13.1 collagen -q13.3 Mild SED with premature AD – COL2A1 Type II 120140 onset arthrosis 12q13.1 collagen -q13.3 Stickler dysplasia AD 108300 + COL2A1 Type II 120140 (heterogeneous, some not 12q13.1 collagen linked to COL2A1) -q13.3

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth 9. Type XI collagenopathies Stickler dysplasia AD 184840 + 6p21 COL11A1 Type XI 120280 (heterogeneous) collagen AR 215150 + 6p21.30 COL11A2 Type XI 120290 Otospondylomegaepiphys collagen eal dysplasia (OSMED) AD + 6p21.3 COL11A2 Type XI 120290 collagen

10. Other spondyloepi-(meta)-physeal [SE(M)D] dysplasias X-linked XLD 313400 – Xp22.2- spondyloepiphyseal p22.1 dysplasia tarda Other late-onset AR 271650 – spondyloepi(meta)physeal dysplasias (Irapa) (Namaqualand et al.) Progressive AR 208230 – pseudorheumatoid dysplasia Dyggve-Melchior- AR 223800 + Clausen dysplasia Wolcott-Rallison AR 226980 – dysplasia Immuno-osseous AR 242900 + dysplasia-Schimke Opsismodysplasia AR 258480 + Chondrodystrophic AR 258480 + myotonia (Schwartz Jampel), type AR 255800 + 1q36-34 1, type 2 Spondyloepiphyseal AR 271640 + dysplasia with joint laxity Sponastrime dysplasia AR 271510 – SEMD short limb – AR 271665 + abnormal calcification

11. Multiple epiphyseal dysplasias & pseudoachondroplasia Pseudoachondroplasia AD 177170 – 19p12- COMP COMP 600310 13.1 Multiple epiphyseal AD 132400 – dysplasia (MED) (Fairbanks and Ribbing AD 600204 – 19p12- COMP COMP 600310 types) 13.1 Other MEDs ? ? 600969 – 1p32.2- COL9A2 Type IX 120260 33 collagen

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth 12. Chondrodysplasia punctata (stippled epiphyses group) Rhizomelic type AR 215100 + 4p16-p14 PEX7 peroxin-7 601757 Zellweger syndrome AR 214100 + 7q11.23 PEX1 AR 214100 + 6p21.1 PEX6 peroxin-6 601498 AR 214100 + 7q11.23 PEX1 peroxin-1 602136 AR 214100 + 12 PEX5 peroxin-5 AR 214100 + 8q21.1 PEX2 peroxin-2 170993 Conradi-Hünermann type XLD 302950 + Xq28 CPXD X-linked recessive type XLR 302940 + Xp22.3 CPXR Brachytelephalangic type XLR 302940 + Xp22.32 ARSE aryl- E 302950 sulfatase Tibial-metacarpal type AD 118651 + Vitamin K-dependent AR 277450 + coagulation defect Other acquired and genetic disorders including Warfarin embryopathy

13. Metaphyseal dysplasias Jansen type AD 156400 + 3p22- PTHR 168468 p21.1 PTHR/PTH RP Schmid type AD 156500 – 6q21- COL10 120110 q22.3 COL10 chain A1 McKusick type AR 250250 + 9p13 (cartilage-hair hypoplasia)

Metaphyseal anadysplasia XLR? 309645 –

Metaphyseal dysplasia AR 260400 – with pancreatic insufficiency and cyclic neutropenia (Shwachman Diamond) Adenosine deaminase AD 102700 – 20q-13.11 ADA Adenosine 102700 deficiency deaminase Metaphyseal AR 250400 – chondrodysplasia-Spahr type Acroscyphodysplasia AR 250215 – (various types)

14. Spondylometaphyseal dysplasias (SMD) Spondylometaphyseal AD 184252 + dysplasia Kozlowski type Spondylometaphyseal AD 184255 + dysplasia (Sutcliffe type) SMD with severe genu AD 184253 + valgum (includes Schmidt and Algerian types)

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth SMD Sedaghatian type AR + Mild SMD different types – that have not been well delineated 15. Brachyolmia spondylodysplasias Hobaek AR 271530- – (includes Toledo type) 630 Maroteaux type AR – Autosomal dominant type AD 113500 –

16. Mesomelic dysplasias Dychondrosteosis AD 127300 – (Leri-Weill) Langer type (homozygous AR 249700 + dyschondrosteosis) Nievergelt type AD 163400 + Kozlowski-Reardon type AR + Reinhardt-Pfeiffer type AD 191400 + Werner type AD + Robinow type, dominant AD 180700 – Robinow type, recessive AR 268310 – Mesomelic dysplasia with AD 600383 + synostoses

17. Acromelic and acromesomelic dysplasias Acromicric dysplasia AD 102370 + Geleophysic dysplasia AR 231050 + Weill-Marchesani AR 277600 + dysplasia Cranioectodermal AR 218330 + dysplasia Trichorhinophalangeal AD 190350 + 8q24.12 TRPS1 dysplasia, type I Trichorhinophalangeal AD 150230 + TRPS1+ dysplasia, type II 8q24.11 EXT1 (Langer-Giedeon) -q24.13 Trichorhinophalangeal AD 190351 + dysplasia, type III Grebe dysplasia AR 200700 + 20q11.2 CDMP1 cartilage 601146 derived morphogenic

protein 1 Hunter-Thompson AR 201250 + 20q11.2 CDMP1 cartilage 601146 dysplasia derived morphogenic

protein 1

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth

Brachydactyly type AD 112500- + A1-A4 800 Brachydactyly type B AD 113000 + Brachydactyly type C AD 133100 + 21q11 CDMP1 cartilage 601196 derived morphogenic protein 1 AD 12q24 AD 113200 + Brachydactyly type E AD 113000 – Pseudohypopara- 20q13 GNAS1 quanine 139320 thyroidism nucleotide (Albright Hereditary binding Osteodystrophy), protein of various types, see OMIM edenylate cyclase -subunit Acrodysostosis SP 101800 – (AD) Saldino-Mainzer AR 266920 – dysplasia Brachydactyly- AD 112410 + 12p hypertension dysplasia (Bilginturan) Craniofacial AD + conodysplasia Angel-shaped phalango- AD 105835 + epiphyseal dysplasia (ASPED) Acromesomelic dysplasia AR 201250 + Other acromesomelic dysplasias

18. Dysplasias with prominent membranous bone involvement Cleidocranial dysplasia AD 119600 + 6p21 CBFA1 core binding 600211 factor -subunit Osteodysplasty, Melnick- XLD 309350 – Needles Precocious osteodysplasty AR + (terHaar dysplasia) Yunis-Varon dysplasia AR 216340 +

19. Bent-bone dysplasia group Campomelic dysplasia AD 114290 + 7q24.3- SOX9 SRY-box 9 211970 q25.1

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth Kyphomelic dysplasia ?AR 211350 + Stüve-Wiedemann AR 601559 + dysplasia

20. Multiple dislocations with dysplasias AD 150250 + 3p21.1- LARI p14.1 Larsen-like syndromes AR 245600 + (including La Reunion Island) Desbuquois dysplasia AR 251450 + Pseudodiastrophic AR 264180 + dysplasia

21. multiplex group Mucopolysaccharidosis AR 252800 – 4p16.3 IDA -1- IH Iduronid- ase Mucopolysaccharidosis AR 252800 – 4p16.3 IDA -1- IS Iduronid- ase Mucopolysaccharidosis XLR 309900 – Xq27.3- IDS Iduronate- II q28 2-sulfatase Mucopolysaccharidosis AR 252900 – 17q25.3 HSS Heparan IIIA sulfate sulfatase Mucopolysaccharidosis AR 252920 17q21 N-Ac-- IIIB D-glucos- aminidase Mucopolysaccharidosis AR 252930 – Ac-CoA: IIIC -glucos- aminidase- N-acetyl- transferase AR 252940 – 12q14 GNS N-Ac- Mucopolysaccharidosis glucos- IIID amine-6- sulfatase Mucopolysaccharidosis AR 230500 – 16q24.3 GALNS Galactose- IVA 6-sulfatase Mucopolysaccharidosis AR 230500 – 3p21.33 GLBI - IVB Galactosid -ase Mucopolysaccharidosis AR 253200 – 5q13.3 ARSB VI Arylsulfat ase B

187 APPENDIX 2 ______

(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth Mucopolysaccharidosis AR 253200 – 7q21.11 GUSB - VII Glucuronid- ase Fucosidosis AR 230000 – 1p34 FUCA - Fucosidase - Mannosidosis AR 248500 – MAN -Mannosid- 19p13.2 ase -q12 - Mannosidosis AR 248510 – 4 MANB -Mannosid- ase Aspartylglucosaminuria AR 208400 – 4q23- AgA Aspartyl- q27 glucos- aminidase GM1 Gangliosidosis, AR 230500 + 3p21- GLB1 -Galactos- several forms p14.2 idase Sialidosis, AR 256550 +/– 6p21.3 NEU -Neuramin- several forms idase Sialic acid storage disease AR 269920 +/– 6q14- SIASD q15

Galactosialidosis, AR 256540 20q13.1 PPGB -Galact- several forms osidase protective protein Multiple sulfatase AR 272200 +/– Multiple deficiency sulfatases Mucolipidosis II AR 252500 + 4q21-23 GNPTA N-Ac- Glucosamine phosphotran sferase Mucolipidosis III AR 252600 – 4q21-23 GNPTA N-Ac- Glucosamine phosphotans ferase

22. Osteodysplastic slender bone group Type I osteodysplastic AR 210710 + dysplasia Type II osteodysplastic AR 210720 + dysplasia Microcephalic AR osteodysplastic dys. 23. Dysplasias with decreased bone density Osteogenesis imperfecta I AD 166200 +/– 17q21 COL1A1 (1) I pro- 120150 (without opalescent teeth) collagen Osteogenesis imperfecta I AD 166240 +/– 17q21 COL1A1 (1)I pro- 120150 (with opalescent teeth) collagen

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth AD 166240 +/- 7q22.1 COL1A2 (2)I pro- 120160 collagen Osteogenesis imperfecta AD 166210 + 17q21 (1)I 120150 II COL1A procollag 1 en AD 166210 + 7q22.1 COL1A2 (2)I pro- 120160 collagen AR 259400 + 17q21 COL1A1 (1)I pro- 120150 collagen Osteogenesis imperfecta AD 259420 + 17q21 COL1A1 (1)I pro- 120150 III collagen AD 259420 + 7q22.1 COL1A2 (2)I pro- 120160 collagen AR 259420 + 7q22.1 CO L1A2 (2)I pro- 120160 collagen AR 259420 + Osteogenesis imperfecta AD 166220 + 7q22.1 COL1A2 (2)I pro- 120160 IV collagen (without opalescent teeth) AD 166220 + 17q21 COL1A1 (1)I pro- 120150 collagen Osteogenesis imperfecta AD 166220 + 7q22.1 COL1A2 (2)I pro- 120160 IV collagen (with opalescent teeth) AD 166220 + 17q21 COL1A1 (1)I pro- 120150 collagen Cole-Carpenter dysplasia SP 112240 + Bruck dysplasia AR 259450 + Singleton-Merton AR dysplasia Osteopenia with AD 166260 radiolucent lesions of the mandible Osteoporosis- AR 259770 – 11q12- pseudoglioma dysplasia q13 Geroderma AR 231070 – osteodysplasticum Hyper IGE syndrome AR 147060 – with osteopenia Idiopathic juvenile SP 259750 – osteroporosis

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth 24. Dysplasias with defective mineralization Hypophosphatasia- AR 241500 + 1p36.1- ALPL alkaline 171760 perinatal lethal and p34 phosphat-ase infantile forms Hypophosphatasia adult AD 146300 – 1p36.1- form p34 Hypophosphatemic XLD 307800 – Xp22.2- PHEX X-linked 171760 rickets p22.1 hypophos- phatemia protein Neonatal AR 239200 + 3q21- CASR calcium 601199 hyperparathyroidism q24, sensor 19p13.3 Transient neonatal AD 145980 + 3q21- CASR calcium 601199 hyperparathyrodism with q24 sensor hypocalciuric hypercalcemia AD + 19p13.3

25. Increased bone density without modification of bone shape Osteopetrosis Precocious typ4e AR 259700 + 11q12- 13 Delayed type AD 166600 – 1p21 Intermediate type AR 259710 + With renal tubular AR 259730 + 8q22 CA2 carbonic acidosis anhydrase II Axial osteosclerosis Osteomeso-pyknosis AD 166450 – With bamboo hair AR 266500 – Pyknodysos AR 265800 + 1q21 CTSK cathepsin K 601105 tosis Osteo-sclerosis AD 122900 + Stanescu type Osteopathia striata Isolated SP – With cranial sclerosis AD 166500 – Sponastrime dysplasia AR 271510 + Melorheostosis SP 155950 – Osteopoikilosis AD 166700 – Mixed sclerosing bone SP – dysplasia

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth 26. Increased bone density with diaphyseal involvement Diaphyseal dysplasia AD 131300 – Camurati Engelmann Craniodiaphyseal ?AR 218300, + dysplasia 122860 Lenz Majewski dysplasia SP 151050 + Endosteal hyperostosis van Buchem type AR 239100 – Worth type AD 144750 – Sclerosteosis AR 269500 – With cerebellar AR 213002 + hypoplasia Kenny Caffey dysplasia AD, 127000, – AR 244460 Osteoectasia with AR 39000 – hyperphos-phatasia (Juvenile Pagets) Diaphyseal dysplasia with AR 231095 – anemia Diaphyseal medullary AD 112250 – stenosis with bone malignancy (Hardcastle)

27. Increased bone density with metaphyseal involvement Pyle dysplasia AR 265900 – Craniometaphyseal dysplasia Severe type AR 218400 + Mild type AD 123000 – 5p15.2- p14.2 Other types Frontometaphyseal XLR 305620 – dysplasia Dysosteosclerosis AR 224300 – XLR Oculodentoosseous AD 257850 + dysplasia AR 164200 + Trichodentoosseous AD 190320 – 17q21 dysplasia

28. Neonatal severe osteosclerotic dysplasias Blomstrand dysplasia AR 215045 + Raine dysplasia ? 259775 + Prenatal onset Caffey AR 114000 + disease ?

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth 29. Lethal chondrodysplasias with fragmented bones Greenberg dysplasia AR 215140 + Dappled diaphyseal AR + dysplasia Astley-Kendall dysplasia AR +

30. Disorganized development of cartilaginous and fibrous components of the skeleton Dysplasia epiphysealis SP 127800 – hemimelica Multiple cartilaginous AD 133700 – 8q23- EXT1 exostosin- exostoses q24.1 1 AD 133701 – 11p12- EXT2 exostosin- p11 2 AD 600209 – 19p EXT3 Enchondromatosis, Ollier SP 166000 – Enchondromatosis with SP 166000 – hemangiomata (Maffucci) Spondyloenchondro- AR 271550 – matosis Spondyloenchondro- AR – matosis with basal ganglia calcification – Dysspondyloenchondro- matosis Metachondroma-tosis AD 156250 Osteoglophonic dysplasia AD 166250 + Genochondromatosis AD 166000 – Carpotarsal AD 127820 – osteochondromatosis Fibrous dysplasia SP 174800 – 20q13 GNAS1 guanine 139320 (McCune-Albright and mosaic nucleotide others) protein, subunit Jaffe Campanucci SP Fibrodysplasia ossificans AD 135100 + 14q22- BMP4 bone 4 progressiva q23 morphoge 112262 nic protein

Cherubism AD 118400 – Cherubism with gingival AR 135300 – fibromatosis

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(Continued from Mode OMIM Pre- Chrom- Gene Protein OMIM previous page) of Syn- sent osomal Gene/ Inher- drome at Locus Protein itance Birth 31. Osteolyses Multicentric predominantly carpal & tarsal in the hand Multicentric carpal-tarsal AD 166300 – osteolysis with and without nephropathy Shinohara carpal-tarsal – osteolysis Multicentric predominantly carpal, tarsal and interphalangeal Francois syndrome AR 221800 – Winchester syndrome AR 277950 – Torg syndrome AR 259600 – Whyte Hemingway AD – carpal-tarsal phalangeal osteolyses Predominantly distal phalanges Hadju-Cheney syndrome AD 102500 – Giacci familial AR 201300 – neurogenic acroosteolysis Mandibulo acral AR 248370 – syndrome Predominantly involving diaphyses and metaphyses Familial expansile AD 174810 – osteolysis 18q21.1 -q22 Juvenile hyaline AR 228600 + fibromatosis

32. Patella dysplasias patella dysplasia AD 161200 – 9q34.1 NPS1 Scypho-patellar dysplasia AD +

193