Century of Jackson-Weiss syndrome: Further definition of clinical and radiographic findings in "lost" descendants of the original kindred

Jackson-Weiss syndrome (JWS) is a condition consisting of craniosynostosis characterized by premature fusion of the cranial sutures and/or characteris tic radiographic anomalies of the feet. The condition is inherited as an au tosomal dominant trait with high penetrance and variable expressivity, Six different mutations in the fibroblast growth factor receptor 2 have been id entified in patients with the clinical diagnosis of JWS. Jabs et al. [1994: Nat Genet 8:275-279] identified an Ala344Gly substitution in two branches of the family in which the clinical syndrome was originally described. This is the only publication to document this mutation in a family with the cli nical diagnosis of JWS. In this study, we have identified a previously unre cognized branch of the original family with individuals that meet the clini cal criteria for the diagnosis of JWS, We demonstrate that a mutation that produces the Ala344Gly substitution is present in affected members. This fa mily illustrates the widely variable expression of the mutation, including a novel phenotype in the proband with a leg-length discrepancy and unilater al absence of the fifth digital ray in her right foot. We identify the clin ical and detailed radiographic features of each affected individual and off er considerations when making the diagnosis of JWS. (C) 2001 Wiley-Liss, In c.