Premature calvarial synostosis and epidermal hyperplasia (Beare-Stevenson syndrome-like anomalies) resulting from a P250R missense mutation in the gene encoding fibroblast growth factor receptor 3

We report on a patient with a severe premature calvarial synostosis and epi dermal hyperplasia. The phenotype was consistent with that of a mild presen tation of Beare-Stevenson syndrome but molecular analysis of the IgIII-tran smembrane linker region and the transmembrane domain of the gene encoding t he FGFR2 receptor, revealed wild-type sequence only. Subsequently, molecula r analysis of the FGFR3 receptor gene identified a heterozygous P250R misse nse mutation in both the proposita and her mildly affected father. This com munication extends the clinical spectrum of the FGFR3 P250R mutation to enc ompass epidermal hyperplasia and documents the phenomenon of activated FGFR receptors stimulating common downstream developmental pathways, resulting in overlapping clinical outcomes. (C) 2001 Wiley-Liss, Inc.