FaCD Online Syndrome Fact Sheet

Last updated: 28 Mar 2008

Name: Simpson-Golabi-Behmel syndrome

Synonym: SGBS

Mode of Inheritance: XL

Genes

GPC3, mapped to Xq26

Tumor features

hepatoblastoma
neuroblastoma, adrenal
Wilms' tumor (nephroblastoma)

Tumor features (possible)

hepatocellular cancer (hepatoma)
lipoma
rhabdomyosarcoma
testicular gonadoblastoma

Non-tumor features

advanced bone age
cleft lip
cleft palate
cryptorchism
dental abnormalities
developmental delay/mental deficiency/mental retardation
gigantism/overgrowth
heart, congenital defect
hypertelorism
hypotonia
macrocephaly
mouth, large (macrostomia)
nails, hypoplastic
nasal bridge, broad
nose, short
palpebral fissures, downward slanting
polydactyly, postaxial
polythelia (supernumerary nipples)
renal cysts
renal dysplasia
tongue, macroglossia
vertebral anomalies

Comment

This disorder is characterized by overgrowth, macroglossia, organomegaly, facial dysmorphisms, congenital heart defects, vertebral anomalies, midline defects and mental deficiency. [1-5]. Patients have an increased risk to develop embryonic neoplasia: Wilms tumor, neuroblastoma, hepatoblastoma[9,11] and possibly, gonadoblastoma and rhabdomyosarcoma[10]. Lapunzia et al.[6] reported on a 3 year old boy with Simpson-Golabi-Behmel syndrome who was diagnosed with hepatocellular cancer. The boy also had a lipoma on his forehead and in the corpus callosum. The gene responsible for Simpson-Golabi-Behmel syndrome has been identified[4;7;8]

Some patients clinically diagnosed with Perlman or Sotos syndrome have mutations in GPC3[11].

References

[1] Golabi M, Rosen L. A new X-linked mental retardation-overgrowth syndrome. Am J Med Genet 1984; 17:345-358.
[2] Behmel A, Plochl E, Rosenkranz W. A new X-linked dysplasia gigantism syndrome: identical with the Simpson dysplasia syndrome? Hum Genet 1984; 67:409-413.
[3] Simpson JL, LAndey S, New M, German J. A previously unrecognized X-linked syndrome of dysmorphia. Birth Defects 1975; XI(2):18-24.
[4] Hughes-Benzie RM, Pilia G, Xuan JY, Hunter AGW, 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. Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families. Am J Med Genet 1996; 66:227-234.
[5] Neri G, Gurrieri F, Zanni G, Lin A. Clinical and molecular aspects of the Simpson-Golabi-Behmel syndrome. Am J Med Genet 79[4], 279-283. 1998.
[6] Lapunzina P, Badia I, Galoppo C, De Matteo E, Silberman P, Tello A, Grichener J, Hughes-Benzie R. A patient with Simpson-Golabi-Behmel syndrome and hepatocellular carcinoma. J Med Genet 1998; 24:153-156.
[7] Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet 1996; 12:241.
[8] Lindsay S, Ireland M, O'Brien O, Clayton-Smith J, Hurst JA, Mann J, Cole T, Sampson J, Slaney s, Schlessinger D, Burn J, Pilia G. Large scale deletions in the GPC3 gene may account for a minority of cases of Simpson-Golabi-Behmel syndrome. J Med Genet 1997; 34:480-483.
[9] Buonuomo PS, Ruggiero A, Vasta I, Attinà G, Riccardi R, Zampino G. Second case of hepatoblastoma in a young patient with Simpson-Golabi-Behmel syndrome. Pediatric hematology and oncology 2005 Oct-Nov; 22(7):623-8.
[10] Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. American journal of medical genetics. Part C, Seminars in medical genetics 2005; 137(1):53-71.
[11] Li M, Shuman C, Fei YL, Cutiongco E, Bender HA, Stevens C, Wilkins-Haug L, Day-Salvatore D, Yong SL, Geraghty MT, Squire J, Weksberg R. GPC3 mutation analysis in a spectrum of patients with overgrowth expands the phenotype of Simpson-Golabi-Behmel syndrome. American journal of medical genetics 2001; 102(2):161-8.