Nosology and classification of genetic skeletal disorders: 2006 revision

Authors

  • Andrea Superti-Furga,

    Corresponding author
    1. Center for Pediatrics and Adolescent Medicine, Department of Pediatrics, University of Freiburg, Freiburg, Germany
    • Center for Pediatrics and Adolescent Medicine, University Hospital, Mathildenstr. 1, DE-79106 Freiburg, Germany.
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  • Sheila Unger

    1. Center for Pediatrics and Adolescent Medicine, Department of Pediatrics, University of Freiburg, Freiburg, Germany
    2. Institute for Human Genetics, University of Freiburg, Freiburg, Germany
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  • How to cite this article: Superti-Furga A, Unger S, and the Nosology Group of the International Skeletal Dysplasia Society. 2007. Nosology and classification of genetic skeletal disorders: 2006 revision. Am J Med Genet Part A 143A:1–18.

  • This paper was prepared by Drs. Superti-Furga and Unger on behalf of the International Skeletal Dysplasia Society and in collaboration with the 2006 Nosology Group: Peter Beighton*, Cape Town; Luisa Bonafé*, Lausanne; Nancy Braverman*, Baltimore; Michael Briggs, Manchester; Dan Cohn, Los Angeles; Valérie Cormier-Dairé*, Paris; Clair Francomano*, Baltimore; Christine Hall*, London; William Horton*, Portland; Ilkka Kaitila, Helsinki; Deborah Krakow, Los Angeles; Ralph Lachman*, Los Angeles; Brendan Lee, Houston; Martine LeMerrer*, Paris; Geert Mortier*, Gent; Stephan Mundlos*, Berlin; Gen Nishimura*, Tokyo; Andrew Poznanski*, Chicago; David Rimoin*, Los Angeles; Stephen Robertson*, Dunedin; Ravi Savarirayan*, Melbourne; Jürgen Spranger*, Mainz; David Sillence*, Sydney; Andrea Superti-Furga*, Freiburg; Sheila Unger*, Freiburg; Matthew Warman, Boston; William Wilcox, Los Angeles; Andrew Wilkie, Oxford; Bernhard Zabel*, Freiburg; Andreas Zankl*, Lausanne. Members marked with an asterisk participated in the compilation workshop held at the 7th ISDS meeting in Martigny (www.isds.ch).

Abstract

The objective of the paper is to provide the revision of the Nosology of Constitutional Disorders of Bone that incorporates newly recognized disorders and reflects new molecular and pathogenetic concepts. Criteria for inclusion of disorders were (1) significant skeletal involvement corresponding to the definition of skeletal dysplasias, metabolic bone disorders, dysostoses, and skeletal malformation and/or reduction syndromes, (2) publication and/or MIM listing, (3) genetic basis proven or very likely, and (4) nosologic autonomy confirmed by molecular or linkage analysis and/or distinctive diagnostic features and observation in multiple individuals or families. Three hundred seventy-two different conditions were included and placed in 37 groups defined by molecular, biochemical and/or radiographic criteria. Of these conditions, 215 were associated with one or more of 140 different genes. Nosologic status was classified as final (mutations or locus identified), probable (pedigree evidence), or bona fide (multiple observations and clear diagnostic criteria, but no pedigree or locus evidence yet). The number of recognized genetic disorders with a significant skeletal component is growing and the distinction between dysplasias, metabolic bone disorders, dysostoses, and malformation syndromes is blurring. For classification purposes, pathogenetic and molecular criteria are integrating with morphological ones but disorders are still identified by clinical features and radiographic appearance. Molecular evidence leads to confirmation of individual entities and to the constitution of new groups, but also allows for delineation of related but distinct entities and indicates a previously unexpected heterogeneity of molecular mechanisms; thus, molecular evidence does not necessarily simplify the Nosology, and a further increase in the number of entities and growing complexity is expected. By providing an updated overview of recognized entities with skeletal involvement and of the underlying gene defects, the new Nosology can provide practical diagnostic help, facilitate the recognition of new entities, and foster and direct research in skeletal biology and genetic disorders. © 2006 Wiley-Liss, Inc.

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