SOTOS SYNDROME

NSD1

Description

Scientific background

Sotos syndrome is an overgrowth syndrome in childhood and is characterized by macrocephaly, distinctive craniofacial features, mild mental retardation (IQ average 76), often premature bone age, and normal height in adulthood. The head shape is narrow and long (dolichocephalic), the forehead high and broad with particularly laterally receding frontal hairline, the chin accentuated and pointed. The distance between the eyes seems widened, the eyelid axes run outward downward. 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 half of them during fever. Congenital malformations such as heart defects are rare. A slightly increased tumor rate has been reported involving various tissues. Increased anxiety is often described as well as hyperactivity and aggressiveness. 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 alterations and about 10% carry deletions. 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.

 

A potential differential diagnosis might be Weaver syndrome (WVS; OMIM 277590), a rare autosomal dominant disorder characterized by tall stature, variable intelligence impairment, and characteristic facial dysmorphia. Pathogenic variants in the EZH2 gene (enhancer of zeste, Drosophila, homolog 2; OMIM 601573) have been found to be causative for a large number of Weaver syndrome cases. However, genetic heterogeneity cannot be excluded.

 

References

Lane & Freeth 2019, Chromatin Signaling and Neurological Disorders, Vol 7, pp. 219 / Tatton-Brown et al., Gene Reviews / 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 Journal of rare diseases 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

GENES

NSD1

ASSOCIATED TESTS

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