Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Sotos Syndrome [Q87.3]

OMIM numbers: 117550, 606681 (NSD1)

Dr. med. Imma Rost

Scientific Background

The Sotos syndrome is characterized by overgrowth during childhood, macrocephaly, typical characteristic craniofacial features, mild intellectual disability (IQ 76 on average), in many cases advanced bone age as well as normal height in adulthood. The head is long and narrow (dolichocephaly), the forehead tall and broad with receding hairline especially at the sides of the head; chin is prominent. The eyes are widely spaced with down-slanting palpebral fissures. The palate is high-arched. Other signs include large hands and feet and frequently joint hyperextensibility. Feeding problems during infancy are common. Approximately 50% of all children have seizures, half of them during fever. Congenital malformations such as cardiac defects are rare. The number of tumor occurrences is said to be slightly higher; various tissues can be affected. Behavior such as anxiety as well as hyperactivity and aggression is common. In 75-90% of all cases Sotos syndrome is caused by mutations or deletions in the NSD1 gene (nuclear-receptor-binding-SET-domain-containing protein 1) in 5q35. Patients in Central Europe and the USA carry point mutations in 60-80%, deletions in approx. 10%. In Japanese patients, microdeletions are the cause of the disease in over 50% of all cases. The frequency of the Sotos syndrome is estimated to be 1:10,000 to 1:50,000. The recurrence risk among siblings is low, since the mutations or deletions are usually de novo.