SIMPSON-GOLABI-BEHMEL SYNDROME

Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked overgrowth disorder characterized by pre- and postnatal overgrowth, minor facial anomalies, skeletal/ For More Information hand anomalies, genitourinary abnormalities and supernumerary nipples. Patients Online Mendelian Inheritance with SGBS also show an increased risk for development of embryonal tumours, in Man http://www.ncbi.nlm.ni especially Wilms’ tumour. The main identified to cause SGBS is called h.gov/omim/ Item# 312870 3 (GPC3) and is located on the X (Xq26). Glypican 3 ap- Item# 300209 pears to play an important role in embryonic growth by regulating cell proliferation and apoptosis.GPC4 (also located at Xq26) has also been implicated in SGBS. GeneReviews online clinical information resource http:ww w.ncbi.nlm.nih.gov/bookshelf/ br.fcgi?book=gene&part=sgbs GENETICS TEST METHODS #sgbs

Males normally have only one X ● Quantitative testing of the GPC3 and To locate a genetics center chromosome in each cell. If that X GPC4 to detect large deletions, near you, please visit the chromosome carries the deletion/point using MLPA (Multiplex Ligation- Canadian Association of mutation in the GPC3 gene, the boy will dependent Probe Amplification) Genetic Counsellors website at be affected with SGBS. As a result, www.cagc-accg.ca or the males are most often affected. Since ● Complete sequencing of the coding National Society of Genetic females have two X , if region and flanking exon/intron Counsellors website at www.nsgc.org one carries the mutation boundaries of the GPC3 gene to identify in the GPC3 gene and the other one point mutations does not, the girl will be a carrier of SGBS. Female carriers may have a EST ENSITIVITY milder phenotype because of the effect T S of Lyonization. GPC3 deletions/mutations have been Affected males will have carrier identified in 40% of SGBS cases. daughters since the X chromosome with the deletion/point mutation will be HO HOULD E ESTED passed from the father to his daughters, W S B T ? 1. Current molecular testing and affected males will have unaffected may not detect all possible ● Individuals clinically suspected of mutations in the GPC3 gene. sons, since they will inherit the father’s Y being affected with SGBS chromosome. If a female is a carrier, her A negative test does not rule out the diagnosis of SGBS, or sons have a 50% chance of inheriting ● Women with a family history of SGBS, eliminate the possibility the the mutation and being affected with to determine carrier status individual is a carrier. SGBS. Her daughters have a 50% chance of inheriting the mutation and ● Pregnancies at risk due to a family 2. Test results should be being carriers themselves, and may history of SGBS interpreted in the context of exhibit milder features of SGBS. clinical findings, family history and other laboratory data.

Potential Outcomes & Interpretation of Test Results 3. This test was developed and its performance characteristics Patient GPC3 Gene validated by the Genome Explanation Sex Mutation Diagnostics Laboratory at the Hospital for Sick Children. It has not been Male None detected This result is unable to confirm a diagnosis of SGBS cleared or approved by the U.S. Food and Drug Administration. The FDA has Male Mutation detected This result confirms a diagnosis of SGBS determined that such clearance or approval is not necessary. This test is used for None detected / Molecular analysis reduces the likelihood Female clinical purposes. none detected that this individual is a carrier of SGBS.

Mutation detected / This individual is a carrier of SGBS, may exhibit a milder Female none detected phenotype, and may transmit a mutation to offspring OMG1620AI/03