SickKids

Paediatric Laboratory Medicine
Paediatric Laboratory Medicine
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Simpson Golabi Behmel Syndrome (SGB)

Background
Who should be tested?
Testing Methodology
Potential Outcomes & Interpretation of Test Results
Cautions
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Background

Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked overgrowth disorder characterized by pre- and postnatal overgrowth, minor facial anomalies, skeletal/hand anomalies, genitourinary abnormalities and supernumerary nipples. Mental retardation is not constantly found and is usually mild. Patients with SGBS also show an increased risk for development of embryonal tumours, especially Wilms’ tumour.

The main gene identified to cause SGBS is called Glypican 3 (GPC3) and is located at Xq26 on the X chromosome. Glypican 3 appears to play an important role in embryonic growth by regulating cell proliferation and apoptosis. Since males have one X chromosome, if that X chromosome carries the deletion/point mutation in the GPC3 gene, the boy will have SGBS. As a result, males are most often affected. Since females have two X chromosomes, if one X chromosome carries the mutation in the GPC3 gene and the other one does not, the girl will be a carrier of SGBS. Female carriers may have a milder phenotype because of the effect of Lyonization.

Affected males will have carrier daughters since the X chromosome with the deletion/point mutation will be passed from the father to his daughters, and affected males will have unaffected sons, since they will inherit the father’s Y chromosome. If a female is a carrier, her sons have a 50% chance of inheriting the mutation and being affected with SGBS. Her daughters have a 50% chance of inheriting the mutation and being carriers themselves, and may exhibit milder features of SGBS.

Approximately 40% of affected males have a deletion in the GPC3 gene. Point mutations in the GPC3 gene have also been reported.

Who should be tested

  • individuals clinically suspected of being affected with SGBS
  • women with a family history of SGBS, to determine the carrier status of unaffected individuals
  • pregnancies at risk due to a family history of SGBS

Testing Methodology

Direct Deletion/Duplication Analysis: All samples are analyzed for the presence of a deletion in the glypican-3 gene by quantitative multiplex PCR analysis of all 8 exons of the gene.

Direct Sequence Analysis: In cases where there is no detectable deletion in the GPC3 gene, direct sequencing of the DNA sample is performed to detect point mutations in the GPC3 gene.

Test Sensitivity: GPC3 deletions/mutations have been identified in 40% of SGBS cases.

Potential Outcomes & Interpretation of Test Results

Patient Sex

GPC3 Gene Mutation

Explanation

Male

none detected

  • This result is unable to confirm a diagnosis of Simpson- Golabi-Behmel Syndrome

Male

mutation detected

  • This result confirms a diagnosis of Simpson-Golabi-Behmel Syndrome

Female

none detected/
none detected

  • Molecular analysis reduces the likelihood that this individual is a carrier of Simpson-Golabi-Behmel Syndrome

Female

mutation detected /
none detected

  • This individual is a carrier of Simpson-Golabi-Behmel Syndrome and may exhibit a milder phenotype

Cautions

  • Current molecular testing may not detect all possible mutations in this gene. A negative test, therefore, does not rule out the diagnosis of SGBS, or eliminate the possibility the individual is a carrier.
  • Test results should be interpreted in the context of clinical findings, family history, and other laboratory data.
  • This test was developed and its performance characteristics validated by the Molecular Genetics Laboratory at the Hospital for Sick Children. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes.

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