Phenotypic spectrum of Simpson-Golabi-Behmel syndrome in a series of 42 cases with a mutation in GPC3 and review of the literature.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked multiple congenital abnormality/intellectual disability syndrome characterized by pre- and post-natal overgrowth, distinctive craniofacial features, macrocephaly, variable congenital malformations, organomegaly, increased risk of tumor and mild/moderate intellectual deficiency. In 1996, Glypican 3 (GPC3) was identified as the major gene causing SGBS but the mutation detection rate was only 28-70%, suggesting either genetic heterogeneity or that some patients could have alternative diagnoses. This was particularly suggested by some reports of atypical cases with more severe prognoses. In the family reported by Golabi and Rosen, a duplication of GPC4 was recently identified, suggesting that GPC4 could be the second gene for SGBS but no point mutations within GPC4 have yet been reported. In the genetics laboratory in Tours Hospital, GPC3 molecular testing over more than a decade has detected pathogenic mutations in only 8.7% of individuals with SGBS. In addition, GPC4 mutations have not been identified thus raising the question of frequent misdiagnosis. In order to better delineate the phenotypic spectrum of SGBS caused by GPC3 mutations, and to try to define specific clinical criteria for GPC3 molecular testing, we reviewed the clinical features of all male cases with a GPC3 mutation identified in the two molecular laboratories providing this test in France (Tours and Paris). We present here the results of the analysis of 42 patients belonging to 31 families and including five fetuses and three deceased neonates. Copyright © 2013 Wiley Periodicals, Inc.

Citation

Edouard Cottereau, Isabelle Mortemousque, Marie-Pierre Moizard, Lydie Bürglen, Didier Lacombe, Brigitte Gilbert-Dussardier, Sabine Sigaudy, Odile Boute, Albert David, Laurence Faivre, Jeanne Amiel, Robert Robertson, Fabiana Viana Ramos, Eric Bieth, Sylvie Odent, Bénédicte Demeer, Michéle Mathieu, Dominique Gaillard, Lionel Van Maldergem, Geneviéve Baujat, Isabelle Maystadt, Delphine Héron, Alain Verloes, Nicole Philip, Valérie Cormier-Daire, Marie-Françoise Frouté, Lucile Pinson, Patricia Blanchet, Pierre Sarda, Marjolaine Willems, Adeline Jacquinet, Ilham Ratbi, Jenneke Van Den Ende, Marylin Lackmy-Port Lis, Alice Goldenberg, Dominique Bonneau, Sylvie Rossignol, Annick Toutain. Phenotypic spectrum of Simpson-Golabi-Behmel syndrome in a series of 42 cases with a mutation in GPC3 and review of the literature. American journal of medical genetics. Part C, Seminars in medical genetics. 2013 May;163(2):92-105

PMID: 23606591

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