Simpson-Golabi-Behmel Syndrome – Definition
Simpson-Golabi-Behmel syndrome (SGBS, OMIM #312870) is an X-linked macrosomia syndrome associated with malformations, reduced intelligence, and an increased risk of developing tumors.
Synonym:
–
Genes:
GPC3 and GPC4 (not all genes known yet)
Gene products:
Glypican-3 (GPC3) and Glypican-4 (GPC4)
Function:
GPC3 and GPC4 are cell-surface-bound proteoglycans
Pattern of inheritance:
X-chromosomal
Prevalence:
Rare
Genotype-phenotype correlation:
Involved are loss-of-function mutations without a known correlation.
Penetrance:
Presumably complete in male carriers of the pathogenic variant. Rarely, female carriers of the pathogenic variant may also be affected.
Simpson-Golabi-Behmel Syndrome – Diagnosis
Diagnosis
The diagnosis is made clinically and can be confirmed with an analysis of the pathogenic variant in patients with a defect in a known gene. Not all SGBS genes are known, so genetic confirmation is not always possible.
Differential Diagnoses
- Beckwith-Wiedemann syndrome spectrum
- Sotos syndrome
- Weaver syndrome
- Gorlin syndrome
- Fryns syndrome
- Perlman syndrome
- Nevo syndrome
- Marshall-Smith syndrome
- Elejalde syndrome
- Infant of a diabetic mother syndrome
- Mosaic trisomy 8
- Mosaic tetrasomy 12p (or Pallister-Killian syndrome)
Clinical Presentation
SGBS is characterized by pre- and postnatal macrosomia, typical craniofacial changes (with macrocephaly, coarse facial features, macrostomia, macroglossia, palatal anomalies), and often mild to severe intellectual impairment with or without structural brain changes. Other variable characteristics include a supernumerary nipple, rectus diastasis/umbilical hernia, diaphragmatic hernia, congenital heart defects, urogenital malformations, and gastrointestinal (GI) anomalies. Skeletal anomalies (vertebral fusion, scoliosis, rib anomalies, hip dysplasia) and hand anomalies (large hands and post-axial polydactyly) may also be present.
The following tumors have been described in patients with SGBS: Wilms tumors and nephroblastomatosis, liver tumors, and neuroblastoma. One child with SGBS and medulloblastoma was described.
Special Features of Treatment
Complex, multi-professional. There are no known special features for cancer treatment.
Diagnosis of Simpson-Golabi-Behmel Syndrome- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of Simpson-Golabi-Behmel Syndrome - What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
According to the latest AACR guidelines, the following screening tests are recommended for patients with Simpson-Golabi-Behmel syndrome:
- Physical examination every 6 months
- Wilms’ tumour: Sonography of the kidneys every 3 months from birth to 7 years of age
- Hepatoblastoma: Abdominal ultrasound + AFP measurement every 3 months from birth until the age of 3 years
