Simpson-Golabi-Behmel Syndrome: GPC3 Sequencing, GPC3 and GPC4 Deletion/Duplication Analysis

Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked overgrowth disorder characterized by pre- and postnatal overgrowth, minor facial anomalies, skeletal/hand anomalies, genitourinary abnormalities and supernumerary nipples. Intellectual disability is not constantly found and is usually mild. Patients with SGBS also show an increased risk for development of embryonal tumours, especially Wilms’ tumour.

The main gene identified to cause SGBS is called Glypican 3 (GPC3) and is located at Xq26 on the X chromosome. Glypican 3 appears to play an important role in embryonic growth by regulating cell proliferation and apoptosis. Since males have one X chromosome, if that X chromosome carries the deletion/point mutation in the GPC3 gene, the boy will have SGBS. As a result, males are most often affected. Since females have two X chromosomes, if one X chromosome carries the mutation in the GPC3 gene and the other one does not, the girl will be a carrier of SGBS. Female carriers may have a milder phenotype because of the effect of Lyonization.

Affected males will have carrier daughters since the X chromosome with the deletion/point mutation will be passed from the father to his daughters, and affected males will have unaffected sons, since they will inherit the father’s Y chromosome. If a female is a carrier, her sons have a 50% chance of inheriting the mutation and being affected with SGBS. Her daughters have a 50% chance of inheriting the mutation and being carriers themselves, and may exhibit milder features of SGBS.

Approximately 40% of affected males have a deletion in the GPC3 gene. Point mutations in the GPC3 gene have also been reported.

See related information sheet: Simpson-Golabi-Behmel Syndrome