What is Sotos Syndrome?
Sotos Syndrome is a rare genetic disorder characterised by excessive physical growth during the first years of life. Excessive growth often starts in infancy and continues into the early teen years. The condition may be accompanied by other conditions such as autism, mild to severe intellectual disability and learning delays, delayed motor, cognitive and social development, hypotonia (low muscle tone) and speech delays or impairments. Children with Sotos syndrome tend to be large at birth and are often taller, heavier and have relatively large skulls (macrocephaly) than is normal for their age.
Signs of the disorder, which vary among individuals, include a disproportionately large skull with a slightly protrusive forehead, large hands and feet, large mandible, hypertelorism (an abnormally increased distance between the eyes) (large inter-pupillary distance), and downslanting eyes. Clumsiness, an awkward gait and unusual aggressiveness or irritability may also occur. Although most cases of Sotos syndrome occur sporadically, familial cases have also been reported. It is similar to Weaver Syndrome. For a quick overview you can watch this 3 minute video.
Signs and Symptoms
This syndrome is characterized by overgrowth and advanced bone age. Affected individuals are dysmorphic, with macrodolichocephaly, downslanting palpebral fissures and a pointed chin. The facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers, and have an unusually large skull and large head. Adult height is usually in the normal range, although Broc Brown has the condition and was named the world’s tallest teenager. As of late 2016, he was 7’8″ and still growing.
Mutations in the NSD1 gene cause Sotos syndrome. The NSD1 gene provides instructions for making a protein that is involved in normal growth and development. The function of this protein is unknown, however. In the Japanese population, the most common genetic change leading to Sotos syndrome deletes genetic material from the region of chromosome 5 containing the NSD1 gene. In other populations, small mutations within the NSD1 gene occur more frequently. Genetic changes involving the NSD1 gene prevent one copy of the gene from producing any functional protein. It is unclear how a reduced amount of this protein during development leads to learning disabilities, overgrowth, and the other features of Sotos syndrome.
About 95 percent of Sotos syndrome cases occur by spontaneous mutation. Most of these cases result from new mutations involving the NSD1 gene. A few families have been described with more than one affected family member. These inherited cases enabled researchers to determine that Sotos syndrome has an autosomal dominant pattern of inheritance.