Chapter 10 - Sotos syndrome

Abstract

Sotos syndrome is caused by intragenic mutations of the NSD1 gene or 5q35 microdeletions encompassing nuclear receptor–binding SET domain protein 1 (NSD1) and these abnormalities result in loss of function. The NSD1 gene is involved in chromatin regulation. It encodes SET domain–containing histone methyltransferase. The cardinal features of Sotos syndrome are overgrowth (defined as height and/or head circumference>97th percentile) with advanced bone age, macrocephaly, characteristic facial appearance, and intellectual disability. Although these features are consistent within the Sotos syndrome population, the severity of the phenotype is variable. The majority of individuals with Sotos syndrome have mild-moderate intellectual disability or borderline intellectual functioning. In addition, increased likelihood of autism spectrum disorder, attention-deficit/hyperactivity disorder, anxiety, and aggression/tantrums have been reported in individuals with Sotos syndrome.