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

Identity

Name

Simpson-Golabi-Behmel syndrome

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 IDLast YearTitleAuthors