Genotype-phenotype correlation in patients suspected of having Sotos syndrome

Horm Res. 2004;62(4):197-207. doi: 10.1159/000081063. Epub 2004 Sep 24.


Background: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration.

Methods: Mutation and fluorescence in situ hybridization analysis was performed on blood samples of 59 patients who were clinically scored into 3 groups. Clinical data were compared between patients with and without NSD1 alterations. With logistic regression analysis the best combination of predictive variables was obtained.

Results: In the groups of typical, dubious and atypical Sotos syndrome, 81, 36 and 0% of the patients, respectively, showed NSD1 gene alterations. Four deletions were detected. In 23 patients (2 families) 19 mutations were detected (1 splicing defect, 3 non-sense, 7 frameshift and 8 missense mutations). The best predictive parameters for a NSD1 gene alteration were frontal bossing, down-slanted palpebral fissures, pointed chin and overgrowth. Higher incidences of feeding problems and cardiac anomalies were found. The parameters, delayed development and advanced bone age, did not differ between the 2 subgroups.

Conclusions: In our patients suspected of having Sotos syndrome, facial features and overgrowth were highly predictive of a NSD1 gene aberration, whereas developmental delay and advanced bone age were not.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology*
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology*
  • Female
  • Genotype
  • Heart Defects, Congenital / genetics
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • Pedigree
  • Phenotype*
  • Syndrome


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