Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita

Pseudoachondroplasia (PSACH) and spondyloepiphyseal dysplasia congenita (SE DC) are autosomal dominant forms of short-limb short stature caused by muta tions in genes that encode structural components of the cartilage extracell ular matrix. PSACH results from mutations in the cartilage oligomeric matri x protein (COMP) gene, while SEDC is caused by mutations in the gene for ty pe II procollagen (COL2A1). We report a child with a distinct skeletal dysp lasia due to the combined phenotypes of PSACH and SEDC. The proband's mothe r had PSACH and his father had SEDC. The child was suspected of having both phenotypes on the basis of the severity of his clinical and radiographic f indings, and this was confirmed by molecular analysis. The COMP gene mutati on (C348R), while not previously published, is typical of those in PSACH pa tients, whereas the COL2A1 mutation (T1370M) is somewhat atypical, as it pr edicts an amino acid change within the carboxyl-terminal region of the prot ein. Both mutations segregated with their respective phenotypes within this family. The description and natural history of the double heterozygote phe notype may be useful in counseling families regarding risk and prognosis. ( C) 2001 Wiley-Liss, Inc.