title: Phenotypic spectrum of Simpson-Golabi-Behmel syndrome in a series of 42 cases with a mutation in GPC3 and review of the literature.
abstract: 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.
authors.affiliation: Service de Génétique, Centre Hospitalo‐Universitaire, and UMR INSERM U930, Faculté de Médecine, Université François Rabelais, Tours, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Cottereau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mortemousque
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Moizard
authors.forename: Lydie
authors.initials: L
authors.lastname: Bürglen
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gilbert-Dussardier
authors.forename: Sabine
authors.initials: S
authors.lastname: Sigaudy
authors.forename: Odile
authors.initials: O
authors.lastname: Boute
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.forename: Robert
authors.initials: R
authors.lastname: Robertson
authors.forename: Fabiana
authors.initials: F
authors.lastname: Viana Ramos
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Demeer
authors.forename: Michéle
authors.initials: M
authors.lastname: Mathieu
authors.forename: Dominique
authors.initials: D
authors.lastname: Gaillard
authors.forename: Lionel
authors.initials: L
authors.lastname: Van Maldergem
authors.forename: Geneviéve
authors.initials: G
authors.lastname: Baujat
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maystadt
authors.forename: Delphine
authors.initials: D
authors.lastname: Héron
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Frouté
authors.forename: Lucile
authors.initials: L
authors.lastname: Pinson
authors.forename: Patricia
authors.initials: P
authors.lastname: Blanchet
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Willems
authors.forename: Adeline
authors.initials: A
authors.lastname: Jacquinet
authors.forename: Ilham
authors.initials: I
authors.lastname: Ratbi
authors.forename: Jenneke
authors.initials: J
authors.lastname: Van Den Ende
authors.forename: Marylin
authors.initials: M
authors.lastname: Lackmy-Port Lis
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rossignol
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
mesh_terms: D001145:Arrhythmias, Cardiac / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005877:Gigantism / Q000235:genetics*; D053673:Glypicans / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans