Phenotypic variability in a three-generation Northern Irish family with Sotos syndrome

Clin Dysmorphol. 2011 Oct;20(4):175-181. doi: 10.1097/MCD.0b013e328349182d.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Family Health
  • Female
  • Genetic Association Studies
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Mutation / genetics
  • Northern Ireland
  • Nuclear Proteins / genetics
  • Pedigree
  • Phenotype*
  • Sotos Syndrome / diagnosis*
  • Sotos Syndrome / genetics*
  • Young Adult

Substances

  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • NSD1 protein, human