Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome.

The Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth/multiple congenital anomalies/dysplasia syndrome caused by a mutant X-linked gene. The spectrum of its clinical manifestations is broad, varying from very mild forms in carrier females to infantile lethal forms in affected males. A typically affected male will show tall stature, "coarse" face, supernumerary nipples, congenital heart defect, and generalized muscular hypotonia. Mental development is normal in most cases. There is an increased risk of neoplasia in infancy, especially Wilms tumor. The SGBS gene spans 500 kilobases in the Xq26 region and contains eight exons. It encodes an extracellular proteoglycan, designated glypican 3 (GPC3), capable of interacting with the insulin-like growth factor IGF2. At present, only deletions of various sizes have been found in a number of affected families.