Simpson-Golabi-Behmel syndrome types I and II

Jair Tenorio, Pedro Arias, Víctor Martínez-Glez, Fernando Santos, Sixto García-Miñaur, Julián Nevado, Pablo Lapunzina

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.