Article

Nosology and classification of genetic skeletal disorders: 2006 revision.

Center for Pediatrics and Adolescent Medicine, Department of Pediatrics, University of Freiburg, Freiburg, Germany.
American Journal of Medical Genetics Part A (impact factor: 2.39). 02/2007; 143(1):1-18. DOI:10.1002/ajmg.a.31483 pp.1-18
Source: PubMed

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.

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Keywords

140 different genes
 
37 groups
 
clinical features
 
Constitutional Disorders
 
direct research
 
distinctive diagnostic features
 
genetic disorders
 
linkage analysis
 
metabolic bone disorders
 
molecular mechanisms
 
multiple observations
 
new groups
 
new molecular
 
new Nosology
 
pathogenetic concepts
 
practical diagnostic
 
radiographic appearance
 
significant skeletal component
 
skeletal malformation
 
unexpected heterogeneity