Alias: Cerebral gigantism.
Gene(s) involved: NSD1 gene in the critical region of 5q35.2.
Brief description of disorder: Sotos syndrome, also known as cerebral gigantism, is a childhood overgrowth syndrome characterized by distinctive facial features including prominent forehead, downward slanting palpebral fissures, and pointed chin, macrocephaly and learning disability. The physical characteristics are often accompanied by delayed social, cognitive, language, and motor development. Behavioral disturbances including anxiety, withdrawal, depression, phobias, sleep disturbance, tantrums, aggressiveness, inappropriate speech, and irritability are seen in approximately 60-80% of children diagnosed with Sotos syndrome.
The prevalence of Sotos syndrome is estimated to occur in one in 14,000 live births.
Inheritance pattern: Sotos syndrome is an autosomal dominant disorder, with a de novo incidence of approximately 95%.
Genetics: Sotos syndrome is caused by haploinsufficiency of the NSD1 (nuclear receptor binding SET domain protein 1) gene, encoding for a coregulator of nuclear receptors that can activate or repress transcription. Point, nonsense, and frameshift mutations, partial NSD1 gene deletions, and microdeletions in 5q35 encompassing NSD1, have been implicated in Sotos syndrome. It has been reported that between 80 and 90% of affected individuals have a mutation or deletion in NSD1. Microdeletions are found in half of affected individuals of Japanese heritage, and in 10% of affected individuals of non-Japanese heritage.
Test method: Conventional cytogenetic analysis, FISH, and array. Gene mutation testing for this disorder is not available at this lab.
Test sensitivity: FISH and array will detect 98-100% of deletions/ duplications that are greater than 100 kb, including 5q35 microdeletions encompassing NSD1. However, deletions/ deletions smaller than 100kb will not be detected by array and deletions/ duplications that are smaller than the FISH probe will not be detected by FISH.
Specimen requirements for Cytogenetic Analysis, FISH and Array:
Adult: 3-5 ml peripheral blood in a sodium-heparin tube.
Newborn: 1-3 ml blood in a sodium-heparin tube.
Turn-around-time
Newborns: 2-3 days
Non-STAT: 2-14 days
FISH: 6-8 days
Array: 7-14 days
References: GeneReviews
Revised 5-24-2011
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