Simpson-Golabi-Behmel Syndrome
Simpson-Golabi-Behmel Syndrome (SGBS)
Overview
Simpson-Golabi-Behmel Syndrome is an X-linked overgrowth condition characterized by pre- and postnatal macrosomia, distinctive craniofacial features, and multiple congenital anomalies. It results from mutations in the GPC3 gene (and rarely GPC4) on chromosome Xq26.
Key Points
- Inheritance: X-linked recessive
- Gene: GPC3 (primary) / GPC4 (rare)
- Prevalence: Rare (< 1/1,000,000)
- Gender: Primarily affects males
- Age of Onset: Prenatal/Birth
Clinical Features
Growth & Development
- Macrosomia (pre- and postnatal)
- Advanced bone age
- Accelerated growth velocity
- Variable developmental delay (30-40% cases)
Craniofacial Features
- Coarse facies
- Macrocephaly
- Hypertelorism
- Macrostomia
- Macroglossia
- Grooved tongue
- Palatal abnormalities
- Supernumerary nipples
Skeletal Manifestations
- Vertebral abnormalities
- Pectus excavatum
- Hand anomalies (broad, short)
- Polydactyly (variable)
Internal Organ Involvement
- Congenital heart defects (25%)
- Renal abnormalities (35%)
- Hepatomegaly
- Splenomegaly
Associated Risks
- Embryonal tumors (8-10%)
- Wilms tumor
- Hepatoblastoma
- Neuroblastoma
- Increased neonatal mortality (~ 10%)
Diagnosis & Genetics
Diagnostic Criteria
- Clinical features
- Family history
- Molecular genetic testing
- Prenatal ultrasound findings
Genetic Testing
- GPC3 gene sequencing
- Deletion/duplication analysis
- X-chromosome analysis
- GPC4 testing if GPC3 negative
Differential Diagnosis
- Beckwith-Wiedemann syndrome
- Sotos syndrome
- Weaver syndrome
- Bannayan-Riley-Ruvalcaba syndrome
Management & Surveillance
Initial Evaluation
- Complete physical examination
- Cardiac assessment
- Renal ultrasound
- Developmental assessment
- Genetic counseling
Ongoing Monitoring
- Regular growth monitoring
- Developmental assessments
- Cardiac follow-up if indicated
- Tumor surveillance protocol:
- Abdominal ultrasound every 3-4 months until age 8
- Alpha-fetoprotein monitoring
- Annual physical examination
Support & Intervention
- Physical therapy
- Occupational therapy
- Speech therapy if needed
- Educational support
- Family support services
