Simpson-Golabi-Behmel syndrome

2002-05-01   Daniel Sinnett 

Division of Hematology-oncology, Research Centre, Sainte-Justine Hospital, 3175 Côte Sainte-Catherine, Montreal, H3T 1C5, Québec, Canada



Simpson-Golabi-Behmel syndrome


X-linked with heterogeneity ; most families map Xq26 ; one large pedigree maps to Xp22


300209 , 312870




373 Simpson-Golabi-Behmel syndrome




Phenotype and clinics

  • Characterized by a wide variety of clinical manifestations including pre-natal and post-natal overgrowth syndrome
  • SGBS is phenotypically similar to Beckwith-Wiedemann syndrome (BWS) suggesting that at least part of the SGBS phenotype could be due to increased IGF-II signalling.
  • Xq26: coarse facieses with mandibular overgrowth, cleft palate, heart defects, hernias, supernumerary nipples, renal and skeletal abnormalities.
  • Xp22: lethal form, multiple anomalies, hydrops fetalis, death within first 8 weeks of life.
  • Neoplastic risk

  • increased risk of embryonal tumors, including Wilms tumor, neuroblastoma ; one case of hepatocellular carcinoma reported
  • Genes involved and Proteins


    GPC3 is highly expressed in embryonal tissues such as the developing intestine and the mesoderm-derived tissues, and its expression is downregulated in most adult tissue, implying a potential role in development. GPC3 is a heparan sulfate proteoglycan (HSPG) that is attached to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor.


    HSPGs of the cell surface are highly interactive macromolecules playing various roles in cell migration, proliferation, differentiation and adhesion, and participating in many developmental and pathological processes.


    Most cases are caused by deletions of different exons in the GPC3 genes . The exact role of GPC3 in the etiology of SGBS is still unknown. The renal dysplasia observed in both SGBS patients and GPC3-deficient mice could be explained by the participation of GPC3 in the control of renal branching morphogenesis by modulating the actions of several different growth factors, including BMP2, BMP7 and fibroblast growth factor 7.


    Pubmed IDLast YearTitleAuthors
    104415861999Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome.Brzustowicz LM et al
    83704711993Integral membrane heparan sulfate proteoglycans.David G et al
    112865012001Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition.DeBaun MR et al
    93896461997Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes.Eggenschwiler J et al
    31855471988Isolation of a cDNA corresponding to a developmentally regulated transcript in rat intestine.Filmus J et al
    111809502001Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis.Grisaru S et al
    89583361996Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.Hughes-Benzie RM et al
    95073971998A patient with Simpson-Golabi-Behmel syndrome and hepatocellular carcinoma.Lapunzina P et al
    97819041998Molecular genetics of Wiedemann-Beckwith syndrome.Li M et al
    106566892000Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma.Murthy SS et al
    97819081998Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome.Neri G et al
    109644732000glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development.Paine-Saunders S et al
    98539641998Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome.Pellegrini M et al
    85897131996Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.Pilia G et al
    107166252000Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions.Tumova S et al