SOTOS SYNDROME

Scientific background

Sotos syndrome is an overgrowth syndrome of childhood that is characterized by macrocephaly, distinctive craniofacial features, mild intellectual disability (IQ average 76), advanced bone age, and normal height in adulthood. The head is narrow and long (dolichocephalic), the forehead high and broad with a laterally receding frontal hairline, and the is chin accentuated and pointed. The distance between the eyes seems widened, and the eyelids slope downwards. The palate is pointed and high. Hands and feet are large, and the joints are often hyperextensible. Feeding problems are common in infancy. About 50% of the children have seizures, and about half of them occur with fever. Congenital malformations such as heart defects are rare. A slightly increased tumor rate has been reported involving various tissues. Increased anxiety, hyperactivity and aggressiveness are often described.

In 75-90% of cases, Sotos syndrome is caused by nucleotide alterations or deletions in the NSD1 gene (nuclear receptor-binding SET domain-containing protein 1) in 5q35. In Central Europe and the USA, 60-80% of patients carry nucleotide changes and about 10% carry deletions, while in Japanese patients, microdeletions are causal in over 50%. The frequency of Sotos syndrome is estimated at 1:10,000 to 1:50,000. The recurrence risk for siblings is low because the nucleotide changes or deletions are mostly new.

Weaver syndrome offers a potential differential diagnosis.

References

Lane & Freeth 2019, Chromatin Signaling and Neurological Disorders, Vol 7, pp. 219 / Tatton-Brown et al., Sotos Syndrome. 2004 Dec 17 [Updated 2019 Aug 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021 / Imagawa et al. 2017, Hum Mutat 38:637 / Leventopoulos et al. 2009, Pediatr Neurol 40:357 / Tatton-Brown et al. 2007, Eur J Hum Genet 15:264 / Baujat et al. 2007, Orphanet J Rare Dis 2:36 / Visser et al. 2005, Am J Hum Genet 76:52 / Rio et al. 2003, J Med Genet 40:436 / Kurotaki et al. 2002, Nat Genet 30:365