Sotos syndrome is an overgrowth disorder with autosomal dominant inheritance caused by mutations and deletions in the nuclear receptor Set domain-containing protein 1 gene. In general, affected individuals have an advanced bone age, macrocephaly, characteristic facial gestalt and learning difficulties. Genotype–phenotype correlations are unclear. Full penetrance is seen and 95% of cases are de novo. Here, we report a three-generation pedigree, with at least eight affected individuals, shown to harbour the nuclear receptor Set domain-containing protein 1 missense mutation c. 6115C>T. To our knowledge, this is the largest Sotos family reported. The observed phenotype is extremely variable, thus highlighting the clinical heterogeneity that may occur.
aNorthern Ireland Regional Genetics Service, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, Northern Ireland
bClinical Genetics Department, Royal Devon and Exeter Hospital, Exeter
cPeninsula Medical School, University of Exeter, Devon, UK
Correspondence to Vivienne P.M. McConnell, MD, Belfast City Hospital, Belfast Health and Social Care Trust, Lisburn Road, Belfast BT9 7AB, UK Tel: +44 289 0263977; fax: +44 289 0236911; e-mail: Vivienne.McConnell@belfasttrust.hscni.net
Received January 4, 2011
Accepted May 16, 2011