Sotos syndrome 1 and 2

Sotos syndrome, described in 1964, was characterized by overgrowth, a distinctive craniofacial configuration, and a non-progressive neurological disorder with mental retardation. There have been many developments since then and an update should be informative. The syndrome is associated with a number of abnormalities: brain, cardiac, urogenital, musculoskeletal (scoliosis), ophthalmologic, dental and neoplastic. It is a genetic disorder due to haploinsufficiency of the NSD1 gene (Nuclear receptor-binding SET Domain protein 1) on chromosome 5q35.2-35.3 in 90% of the patients: Sotos syndrome 1. Recently, heterozygous mutations in the NFIX gene (Nuclear Factor I, X type) on chromosome 19p13.3 were identified in a few children with the Sotos syndrome phenotype: Sotos syndrome 2. Genotype-phenotype correlations have been obtained. Many studies have been conducted to find out the functional pathway and the manner that the mutated genes altered transcription of other genes and the interaction with other proteins to generate the phenotype, but the functional pathway is largely unknown.