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International nomenclature and classification of the osteochondrodysplasias (1997)

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Text of International nomenclature and classification of the osteochondrodysplasias (1997)

  • The International Working Group on Bone Dysplasiasmet in Los Angeles, California on August 5 and 6, 1997,to perform the third official revision of the 1972 Paris No-menclature of Constitutional Disorders of Bone. In thelast revision (1992), the classification was reoriented onradiodiagnostic and morphologic criteria and groupedmorphologically similar disorders into families of dis-orders based on presumed pathogenetic similarities.

    In the present, newly revised nomenclature, the fa-milies of disorders were to some extent rearrangedbased on recent etiopathogenetic information concern-ing the gene and/or protein defect in these disorders. Inthose disorders in which the basic defect was well docu-mented, they were regrouped into distinct families, inwhich the component disorders were due to mutationsin the same gene. These included the achondroplasiagroup of disorders with mutations in fibroblast growthfactor receptor 3; the diastrophic dysplasia group ofdisorders, with mutations in the diastrophic dysplasiasulfate transporter gene; the type II collagenopathies,with mutations in type II collagen; and the type XI col-lagenopathies with mutations in cartilage-oligomericmatrix protein (COMP). Several new groups of disor-

    ders were added, including the lethal skeletal dyspla-sia group with fragmented bones and themiscellaneous neonatal severe dysplasia group. Otherfamilies were renamed, such as the osteodysplasticslender bone group. Because of the large number ofdysplasias with increased bone density, this group wassubdivided into three new families: increased bonedensity without modification of bone shape; increasedbone density with diaphyseal involvement, and in-creased bone density with metaphyseal involvement.

    References for most of the skeletal dysplasias can beobtained through a text such as the third chapter of theTaybi/Lachman book The Radiology of Syndromes,Metabolic Disorders and Skeletal Dysplasias, 4 th Edi-tion, or through on-line access of the Mendelian Inheri-tance in Man (OMIM) on the Internet directly or byaccessing the International Skeletal Dysplasia Web Site( where eachdisorder is hyperlinked to OMIM. Other references fornon-referenced disorders are listed below.

    Ralph S. Lachman International nomenclatureand classification of theosteochondrodysplasias (1997)International Working Groupon Constitutional Diseases of BoneDavid L. Rimoin, MD, Ph. D. (Los Angeles) (Chair); Clair A. Francomano,MD (Bethesda); Andres Giedion, MD (Zurich); Christine Hall, MD (Lon-don); Ilkka Kaitila, MD (Helsinki); Dan Cohn, Ph. D. (Los Angeles); Ro-bert Gorlin, DDS (Minneapolis); Judith Hall, MD (Vancouver); WilliamHorton, MD (Portland); Deborah Krakow, MD (Los Angeles); MartineLe Merrer, MD (Paris); Ralph Lachman, MD (Los Angeles); Stefan Mund-los, MD (Mainz); Andrew K. Posnanski, MD (Chicago); David Sillence,MD (Sydney); Jrgen Spranger, MD (Mainz); Matthew Warman, MD (Cle-veland); Andrea Superti-Furga, MD (Zurich); and William Wilcox, MD(Los Angeles)

    R. S.Lachman ())International Skeletal Dysplasia Registry,Room 1001, 444 S.San Vicente Blvd.,Los Angeles, CA 90048, USA

    The workshop was supported by grantsfrom the National Institutes of Health (HD35637-01); The March of Dimes; SeronoCorporation; Pharmacia-Upjohn, andOceana Investment Co.

    We wish to thank Drs. Pierre Maroteauxand Peter Beighton for their helpful com-ments.

    Pediatr Radiol (1998) 28: 737744 Springer-Verlag 1998

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    SED with brachydactylyReginato AJ, Passano GM, Neumann G,Falasca GF, Diaz-Valadez M, JimenezSA, Williams CJ (1994) Familial spondy-loepiphyseal dysplasia tarda brachydac-tyly and precocious osteoarthritis. ArthRheum 37: 1078

    Mild SED with premature onset arthrosisAnderson IJ, Tsipouras P, Scher C, Ra-mesar RS, Martel W, Beighton P (1990)Spondyloepiphyseal dysplasia, mild au-tosomal dominant type is not due to pri-mary defects of type II collagen. Am JMed Genet 37: 272

    Other late-onset spondyloepi(meta)phy-seal dysplasias Namaqualand typeBeighton P, Christy G, Learmonth D III(1984) Namaqualand hip dysplasia: anautosomal dominant entity. Am J MedGenet 19: 161

    Mesomelic dysplasia, Kozlowski-ReardontypeKozlowski K, Bacha B, Brachimi L,Massen (1993) Mesomelic dysplasia ofthe upper extremities with other ab-normalities. Pediatr Radiol 23: 108

    Reardon W, Hall CM, Slaney S, Huson SM,Connell J, Al-Hilaly N, Fixsen J, Barait-ser M, Winter RM (1993) Mesomeliclimb shortness. Am J Med Genet 47: 788

    Osteogenesis imperfecta with unusual ske-letal lesions (with radiolucent lesions ofthe mandible)Levin LS, Wright JM, Byrd DL, Green-way G, Dorst JP, Irani RN, Pyeritz RE,Young RJ, Laspia CL (1985) Am J MedGenet 21: 257

    Axial osteosclerosisWhyte MP, Fallon MD, Murphy WA,Teitelbaum SL (1981) Axial osteomala-cia. Clinical, laboratory and genetic in-vestigation of an affected mother andson. Am J Med 71: 1041

    Astley-Kendall dysplasiaAstley R, Kendall AC (1980) A bonedysplasia for diagnosis. Ann Radiol 2:121

    Shinohara carpal-tarsal osteolysisShinohara O, Kubot C, Kimira C,Nishimura G, Takahashi S (1991)Essential osteolysis associated withnephropathy, corneal opacity and pul-monary stenosis. Am J Med Genetic41: 482

  • 739

    International nomenclature of constitutional disorders of bone

    Osteochondrodysplasias Mode ofinheritance

    Presentat birth


    Gene Protein

    1. Achondroplasia groupThanatophoric dysplasia, Type I AD + 4p16.3 FGFR3 FGFR3Thanatophoric dysplasia, Type II AD + 4p16.3 FGFR3 FGFR3Achondroplasia AD + 4p16.3 FGFR3 FGFR3Hypochondroplasia AD 4p16.3 FGFR3 FGFR3Other FGFR3 disorders

    2. Spondylodysplastic and other perinatally lethal groupsLethal platyspondylic skeletal dysplasias

    (San Diego type, Torrance type, Luton type) SP +Achondrogenesis type 1A AR +

    3. Metatropic dysplasia groupFibrochondrogenesis AR +Schneckenbecken dysplasia AR +Metatropic dysplasia (various forms) AD +

    4. Short-rib dysplasia (SRP) (with or without polydactyly) groupSRP type I, Saldino-Noonan AR +SRP type II, Majewski AR +SRP type III, Verma-Naumoff AR +SRP type IV, Beemer-Langer AR +Asphyxiating thoracic dysplasia (Jeune) AR +Chondroectodermal dysplasia

    (Ellis-van Creveld dysplasia) AR + 4p16

    5. Atelosteogenesis omodysplasia groupAtelosteogenesis type I

    (includes Boomerang dysplasia) SP +Omodysplasia I (Maroteaux) AD +Omodysplasia II (Borochowitz) AR +Otopalatodigital syndrome type II XLR +Atelosteogenesis type III SP +de la Chapelle dysplasia AR +

    6. Diastrophic dysplasia groupDiastrophic dysplasia AR + 5q32-q33 DTDST Sulfate transporterAchondrogenesis 1B AR + 5q32-q33 DTDST Sulfate transporterAtelosteogenesis type II AR + 5q32-q33 DTDST Sulfate transporter

    7. Dyssegmental dysplasia groupDyssegmental dysplasia

    Silverman-Handmaker typeAR +

    Dyssegmental dysplasiaRolland-Desbuquois type

    AR +

    8. Type II collagenopathiesAchondrogenesis II (Langer-Saldino) AD + 12q13.1-q13.3 COL 2A1 Type II collagenHypochondrogenesis AD + 12q13.1-q13.3 COL 2A1 Type II collagenKniest dysplasia AD + 12q13.1-q13.3 COL 2A1 Type II collagenSpondyloepiphyseal dysplasia (SED) congenita AD + 12q13.1-q13.3 COL 2A1 Type II collagenSpondyloepimetaphyseal dysplasia SEMD

    Strudwick type AD + 12q13.1-q13.3 COL 2A1 Type II collagenSED with brachydactyly AD 12q13.1-q13.3 COL 2A1 Type II collagenMild SED with premature onset arthrorisis AD 12q13.1-q13.3 COL 2A1 Type II collagenStickler dysplasia (heterogeneous, some not

    linked to COL2A1) AD + 12q13.1-q13.3 COL 2A1 Type II collagen

    9. Type XI collagenopathiesStickler dysplasia (heterogeneous) AD + 6p21 COL 11A1 Type XI collagenOtospondylomegaepiphyseal dysplasia AR + 6p21.3 COL 11A2 Type XI collagen

    (OSMED) AD + 6p21.3 COL 11A2 Type XI collagen

    10. Other spondyloepi-(meta)-physeal [SE(M)D] dysplasiasX-linked spondyloepiphyseal dysplasia tarda XLD Xp22.2-p22.1Other late-onset spondyloepi-(meta)-physeal

    dysplasias (Irapa) (Namaqualand, et al.) AR Progressive pseudorheumatoid dysplasia AR

  • 740

    International nomenclature of constitutional disorders of bone (continued)

    Osteochondrodysplasias Mode ofinheritance

    Presentat birth


    Gene Protein

    Dyggve-Melchior-Clausen dysplasia AR +Wolcott-Rallison dysplasia AR Immuno-osseous dysplasia-Schimke AR +Opsismodysplasia AR +Chondrodystrophic myotonia (Schwartz Jampel)

    type 1, type 2AR + 1q36-34

    Spondyloepiphyseal dysplasia with joint laxity AR +Sponastrime dysplasia AR SEMD short limb abnormal calcification AR +

    11. Multiple epiphyseal dysplasias & pseudoachondroplasiaPseudoachondroplasia AD 19p12-13.1 COMP COMPMultiple epiphyseal dysplasia (MED) AD

    (Fairbanks and Ribbing types) AD 19p12-13.1 COMP COMPOther MEDs ? 1p32.2-33 COL 9A2 Type IX collagen

    12. Chondrodysplasia punctata (stippled epiphyses group)Rhizomelic type AR + 4p16-p14 PEX 7 Peroxin-7Zellweger syndrome AR + 7q11.23 PEX 1

    AR + 6p21.1 PEX 6 Peroxin-6AR + 7q11.23 PEX 1 Peroxin-1AR + 12 PEX 5 Peroxin-5AR + 8q21.1 PEX 2 Peroxin-2

    Conradi-Hnermann type XLD + Xq28 CPXDX-linked recessive type XLR + Xp22.3 CPXRBrachytelephalangic type XLR + Xp22.32 ARSE Arylsulfatase ETibial-metacarpal type AD +Vitamin K-dependent coagulation defect AR +

    13. Metaphyseal dysplasiasJansen type AD + 3p22-p21.1 PTHR PTHR/PTHRPSchmid type AD 6q21-q22.3 COL 10A1 COL10 achainMcKusick type (cartilage-hair hypoplasia) AR + 9p13Metaphyseal anadysplasia XLR? Metaphyseal dysplasia with pancreatic

    insufficiency and cyclic neutropenia(Shwachman Diamond) AR

    Adenosine deaminase deficiency AD 20q-13.11 ADA Adenosinedeaminase

    Metaphyseal chondrodysplasia Spahr type


    Acroscyphodysplasia (various types) AR