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Simpson-Golabi-Behmel syndrome

Written2002-05Daniel Sinnett
Division of Hematology-oncology, Research Centre, Sainte-Justine Hospital, 3175 Côte Sainte-Catherine, Montreal, H3T 1C5, Québec, Canada
This article is an update of :
2000-09Hope H Punnett
Genetics Laboratory, St. Christopher's Hospital for Children, Erie Avenue at Front Street, Philadelphia, PA 19134, USA

(Note : for Links provided by Atlas : click)


Atlas_Id 10038
Genes implicated inGPC3   OFD1  
Inheritance X-linked with heterogeneity ; most families map Xq26 ; one large pedigree maps to Xp22


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

    Gene NameGPC3 (glypican 3)
    Location Xq26.2
    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.


    Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome.
    Brzustowicz LM, Farrell S, Khan MB, Weksberg R
    American journal of human genetics. 1999 ; 65 (3) : 779-783.
    PMID 10441586
    Integral membrane heparan sulfate proteoglycans.
    David G
    The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1993 ; 7 (11) : 1023-1030.
    PMID 8370471
    Simpson Golabi Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition.
    DeBaun MR, Ess J, Saunders S
    Molecular genetics and metabolism. 2001 ; 72 (4) : 279-286.
    PMID 11286501
    Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes.
    Eggenschwiler J, Ludwig T, Fisher P, Leighton PA, Tilghman SM, Efstratiadis A
    Genes & development. 1997 ; 11 (23) : 3128-3142.
    PMID 9389646
    Isolation of a cDNA corresponding to a developmentally regulated transcript in rat intestine.
    Filmus J, Church JG, Buick RN
    Molecular and cellular biology. 1988 ; 8 (10) : 4243-4249.
    PMID 3185547
    Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis.
    Grisaru S, Cano-Gauci D, Tee J, Filmus J, Rosenblum ND
    Developmental biology. 2001 ; 231 (1) : 31-46.
    PMID 11180950
    Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.
    Hughes-Benzie RM, Pilia G, Xuan JY, Hunter AG, Chen E, Golabi M, Hurst JA, Kobori J, Marymee K, Pagon RA, Punnett HH, Schelley S, Tolmie JL, Wohlferd MM, Grossman T, Schlessinger D, MacKenzie AE
    American journal of medical genetics. 1996 ; 66 (2) : 227-234.
    PMID 8958336
    A patient with Simpson-Golabi-Behmel syndrome and hepatocellular carcinoma.
    Lapunzina P, Badia I, Galoppo C, De Matteo E, Silberman P, Tello A, Grichener J, Hughes-Benzie R
    Journal of medical genetics. 1998 ; 35 (2) : 153-156.
    PMID 9507397
    Molecular genetics of Wiedemann-Beckwith syndrome.
    Li M, Squire JA, Weksberg R
    American journal of medical genetics. 1998 ; 79 (4) : 253-259.
    PMID 9781904
    Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma.
    Murthy SS, Shen T, De Rienzo A, Lee WC, Ferriola PC, Jhanwar SC, Mossman BT, Filmus J, Testa JR
    Oncogene. 2000 ; 19 (3) : 410-416.
    PMID 10656689
    Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome.
    Neri G, Gurrieri F, Zanni G, Lin A
    American journal of medical genetics. 1998 ; 79 (4) : 279-283.
    PMID 9781908
    glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development.
    Paine-Saunders S, Viviano BL, Zupicich J, Skarnes WC, Saunders S
    Developmental biology. 2000 ; 225 (1) : 179-187.
    PMID 10964473
    Gpc3 expression correlates with the phenotype of the Simpson-Golabi-Behmel syndrome.
    Pellegrini M, Pilia G, Pantano S, Lucchini F, Uda M, Fumi M, Cao A, Schlessinger D, Forabosco A
    Developmental dynamics : an official publication of the American Association of Anatomists. 1998 ; 213 (4) : 431-439.
    PMID 9853964
    Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.
    Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D
    Nature genetics. 1996 ; 12 (3) : 241-247.
    PMID 8589713
    Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions.
    Tumova S, Woods A, Couchman JR
    The international journal of biochemistry & cell biology. 2000 ; 32 (3) : 269-288.
    PMID 10716625


    This paper should be referenced as such :
    Sinnett, D
    Simpson-Golabi-Behmel syndrome
    Atlas Genet Cytogenet Oncol Haematol. 2002;6(4):309-310.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :
    History of this paper:
    Punnett, HH. Simpson-Golabi-Behmel syndrome. Atlas Genet Cytogenet Oncol Haematol. 2000;4(4):221-221.

    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes GPC3

    External links

    OrphanetSimpson-Golabi-Behmel syndrome
    Other databaseSimpson-Golabi-Behmel syndrome (GARD)
    Genes implicated inGPC3   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inOFD1   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

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