Simpson-Golabi-Behmel syndrome

Simpson-Golabi-Behmel syndrome (SGBS), also known as Golabi-Rosen syndrome or Simpson dysmorphia syndrome, is a rare X-linked overgrowth disorder characterized by pre- and postnatal overgrowth, distinctive facial features, and a wide spectrum of congenital anomalies. The condition primarily affects males, while carrier females may show mild or no features. SGBS is caused by mutations in the GPC3 gene (SGBS type 1) or, less commonly, the GPC4 gene (SGBS type 2), both of which encode glypicans involved in growth factor signaling. Key clinical features include macrosomia (large birth weight), macrocephaly, coarse facial features with a broad nasal bridge, wide mouth, macroglossia (enlarged tongue), and midline abnormalities such as cleft lip or palate. Affected individuals may also present with organomegaly (enlarged liver, spleen, and kidneys), skeletal anomalies including extra ribs or vertebral defects, polydactyly, cardiac defects, diaphragmatic hernia, and genitourinary abnormalities such as cryptorchidism and hypospadias. Intellectual disability ranges from absent to severe. A significant concern is the increased risk of embryonal tumors, particularly Wilms tumor, hepatoblastoma, and neuroblastoma, especially in early childhood. Management of Simpson-Golabi-Behmel syndrome is multidisciplinary and symptom-based, as no specific cure exists. Treatment may involve surgical correction of congenital anomalies, cardiac monitoring, and regular tumor surveillance including abdominal ultrasound screening during the first years of life. Developmental support, speech therapy, and educational interventions are recommended for those with intellectual disability. Genetic counseling is essential for affected families to understand recurrence risks and carrier status in females.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Simpson-Golabi-Behmel syndrome