Simpson-Golabi-Behmel syndrome types I and II

Abstract

Simpson-Golabi-Behmel syndrome (SGBS) is a rare overgrowth syndrome clinically characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Abnormalities of the skeletal system, heart, central nervous system, kidney, and gastrointestinal tract may also be observed. Intellectual disability, early motor milestones and speech delay are sometimes present; however, there are a considerable number of individuals with normal intelligence.Genomic rearrangements and point mutations involving the glypican-3 gene (GPC3) at Xq26 have been shown to be associated with SGBS. Occasionally, these rearrangements also include the glypican-4 gene (GPC4). Glypicans are heparan sulfate proteoglycans which have a role in the control of cell growth and cell division.Although a lethal and infrequent form (also known as SGBS type II) has been described, only the classical form of SGBS is reviewed in this work, whereas only some specific features on SGBS type II are commented.We review all clinical and molecular aspects of this rare disorder, updating many topics and suggest a follow-up scheme for geneticists and primary care clinicians.

Interactions of signaling proteins, growth factors and other proteins with heparan sulfate: mechanisms and mysteries

“…For instance, loss-of-function mutations in Glypican-3 cause the human X-linked disorder Simpson-Golabi-Behmel syndrome that is characterized by embryonic and postnatal overgrowth, cardiac malformations and predisposition to certain tumors ( 49,50 ). Abnormally high shedding of syndecan-2 from the cell surface has been linked to progression and malignancy of various human tumors ( 51,52 ).…”

Simpson–Golabi–Behmel syndrome: a prenatal diagnosis in a foetus with GPC3 and GPC4 gene microduplications

“…Mutations and genomic rearrangements involving the GPC3 gene lead to an X-linked overgrowth syndrome called Simpson-Golabi-Behmel type I (SGBS1) (1). One case of a GPC4 duplication linked to SGBS1 has been reported in the literature (2); however, no point mutations or deletions have been described so far.…”

“…Glypicans are involved in signalling pathways associated with cell division and growth regulation (1). The loss of functional GPC3 probably leads to hyperactivation of Hedgehog signalling which could explain overgrowth and increased tumour risk seen in SGBS1 (4).…”

Nonisolated diaphragmatic hernia in Simpson‐Golabi‐Behmel syndrome

“…Male fetuses are affected with the condition, and some carrier female fetuses may be symptomatic due to lyonization; however, most female carriers are phenotypically normal . The classic form of SGBS, type I, is caused by a deletion, duplication, or point mutation in the GPC3 gene encoding glypican‐3 located on chromosome Xq26 . Another form of SGBS, type II, was identified through linkage to Xp22 and associated with a severe phenotype including hydrops fetalis and multiple anomalies.…”

“…5 The classic form of SGBS, type I, is caused by a deletion, duplication, or point mutation in the GPC3 gene encoding glypican-3 located on chromosome Xq26. 6 Another form of SGBS, type II, was identified through linkage to Xp22 and associated with a severe phenotype including hydrops fetalis and multiple anomalies. The PIGA gene has recently been reported to cause this lethal form.…”