Simpson-Golabi-Behmel syndrome

2002-05-01 Daniel Sinnett Affiliation

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

Identity

Name

Inheritance

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

Omim

300209 , 312870

Mesh

C537340

Orphanet

373 Simpson-Golabi-Behmel syndrome

Umls

Clinics

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

Description

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.

Function

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.

Germinal

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.

Bibliography

Pubmed ID	Last Year	Title	Authors
10441586	1999	Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome.	Brzustowicz LM et al
8370471	1993	Integral membrane heparan sulfate proteoglycans.	David G et al
11286501	2001	Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition.	DeBaun MR et al
9389646	1997	Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes.	Eggenschwiler J et al
3185547	1988	Isolation of a cDNA corresponding to a developmentally regulated transcript in rat intestine.	Filmus J et al
11180950	2001	Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis.	Grisaru S et al
8958336	1996	Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.	Hughes-Benzie RM et al
9507397	1998	A patient with Simpson-Golabi-Behmel syndrome and hepatocellular carcinoma.	Lapunzina P et al
9781904	1998	Molecular genetics of Wiedemann-Beckwith syndrome.	Li M et al
10656689	2000	Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma.	Murthy SS et al
9781908	1998	Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome.	Neri G et al
10964473	2000	glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development.	Paine-Saunders S et al
9853964	1998	Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome.	Pellegrini M et al
8589713	1996	Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.	Pilia G et al
10716625	2000	Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions.	Tumova S et al