Progress of research on Sotos syndrome

Sotos syndrome(MIM#117550) is an inherited disease characterized by overgrowth in childhood. The cardinal features are macrocephaly, distinctive facial features, advanced bone age and mental retardation. Hundreds of Sotos cases have been reported so far, but the concrete incidence is not known. Sotos syndrome results from mutations and deletions of the NSD1 gene, located at chromosome 5q35. The NSDl gene encodes the nuclear receptor-binding SET domain-containing protein 1, which is related to the modulation of transcription. About 75% of patients with Sotos sydrome are caused by NSD1 intragenic mutations or microde-letions. The majority of non-Japanese cases of Sotos are caused by NSD1 point mutation, while microdeletions account for about 50% of Japanese patient populations. No genetic abnormalities were found in nearly 25%of cases of Sotos. The accurate pathogenic reason of these cases remain unknown. Point mutations and microdeletions could be detected through direct sequencing, FISH analysis, MLPA and real-time quantitive fluorescent PCR. Most of the mutations are novel ones, most of cases are sporadic and several familial cases were reported. The differential diagnosis of Sotos are those characterised by excessive growth, such as Weaver Syndrome, Beckwith-Wiedemann Syndrome and Fragile-X Syndrome. No ideal therapies aim at Sotos now and symptomatic treatment is the main method to alleviate clinical symptoms. Follow-up in the first year after birth is of great significant for preventing and monitoring clinical complications, including scoliosis, febrile seizure and learning disability and so on. Key words: Sotos syndrome; NSD1 gene; Genotype and phenotype