Sotos syndrome

Sotos syndrome (Sotos–Dodge syndrome, cerebral gigantism) is a rare genetic syndrome characterized by excessive growth during the first years of life. This accelerated growth begins in infancy and slows during early teenage years (by around age 15). Sotos syndrome may be associated with autism, mild intellectual disability, delayed motor, social, and cognitive development, hypotonia, and speech disorders.

Affected children are often larger at birth, with macrocephaly (increased head circumference) and higher body weight compared to peers. Other characteristic features include a disproportionately large skull, prominent forehead, large hands and feet, a large jaw, and hypertelorism (widely spaced eyes).

Diagnosis:
Diagnosis is usually confirmed by genetic testing and laboratory diagnostics, which typically detect a mutation in the responsible gene.

Sotos syndrome occurs sporadically in about 95% of cases, although inherited forms have also been described. In these cases, inheritance is autosomal dominant (one mutated gene is sufficient for the disease to manifest). The mutation is located in the NSD1 gene on chromosome 5. This gene encodes a protein responsible for proper growth and development. Epidemiological data suggest a higher susceptibility in the Japanese population.

The incidence is approximately 1:10,000 to 1:14,000 live births, though it may be underdiagnosed; the true incidence may be as high as 1:5,000.

Adults with Sotos syndrome do not have a reduced life expectancy. Psychomotor, intellectual, and social development often improves during early school years, although coordination, attention, and social difficulties may persist into adulthood.

Treatment:
Treatment is symptomatic and includes early intervention, support of psychomotor development, rehabilitation, and involvement of appropriate specialists depending on the specific symptoms.

• Increased growth in early childhood, continuing into adolescence, with accelerated bone growth
• Disproportionately large skull, prominent and high forehead, red cheeks, narrow face, small and pointed chin
• Downward slanting palpebral fissures
• Height and growth above peers and siblings (deviation from growth curve)
• Tall stature in adulthood
• Large and long hands and feet
• Hypertelorism (increased distance between the eyes)
• Macrocephaly (increased head circumference)
• Clumsiness, abnormal gait
• Mild intellectual disability
• Delayed psychomotor development, often due to hypotonia (reduced muscle tone), with delayed social and cognitive development
• Behavioral disorders such as obsessive-compulsive disorder, ADHD, phobias, impulsivity, and temper outbursts
• Possible autistic features, aggression, and irritability
• Speech and language development difficulties, including sentence formation
• Abnormal intonation and monotonous speech, possibly due to functional vocal cord abnormalities
• Congenital heart defects, kidney defects, scoliosis, hearing and vision disorders, seizures
• Possible neonatal complications such as jaundice and poor feeding
• Increased susceptibility in some individuals to various types of cancer at a young age (statistically observed risk)