Sotos syndrome

Sotos syndrome, also known as cerebral gigantism, is a genetic overgrowth disorder characterized by excessive physical growth during the first years of life, distinctive facial features, and varying degrees of intellectual disability. The condition was first described by Dr. Juan Sotos in 1964. It is caused by mutations or deletions in the NSD1 gene (nuclear receptor binding SET domain protein 1) located on chromosome 5q35, which plays a critical role in regulating gene expression during development. The hallmark features of Sotos syndrome include pre- and postnatal overgrowth with increased height and head circumference (macrocephaly), a characteristic facial gestalt that includes a broad and prominent forehead, sparse frontotemporal hair, downslanting palpebral fissures, malar flushing, a long and narrow face, and a pointed chin. Advanced bone age is a consistent finding. Affected individuals typically experience developmental delay, particularly in motor and speech milestones, and intellectual disability that ranges from mild to severe, though some individuals have normal intelligence. Additional features may include hypotonia, behavioral problems (including features of autism spectrum disorder, anxiety, and ADHD), seizures, cardiac anomalies, renal anomalies, scoliosis, and an increased risk of certain tumors in childhood, though the overall cancer risk remains relatively low. There is no cure for Sotos syndrome, and management is supportive and symptom-based. Early intervention programs including speech therapy, occupational therapy, and physical therapy are important for optimizing developmental outcomes. Regular monitoring for potential complications such as scoliosis, cardiac defects, renal abnormalities, and seizures is recommended. Behavioral and educational support is often beneficial. Genetic counseling is advised for affected families, as most cases arise from de novo mutations, though autosomal dominant transmission from an affected parent can occur.

Common questions about Sotos syndrome