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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. [ABSTRACT FROM AUTHOR]

Aim: Nuclear receptor-binding SET domain-containing protein 1 (NSD1) gene mutations and deletions (NSD1+/-) are the major cause of Sotos syndrome. The aim was to investigate which auxology parameters relate to NSD1+/- in patients clinically suspected of Sotos syndrome.Methods: In 32 patients clinically suspected of Sotos syndrome, we compared auxology parameters between NSD1+/- patients and patients without NSD1 gene alterations (NSD1+/+). The statistical performance of these parameters to predict NSD1+/- was assessed.Results: Arm span-for-height standard deviation score (SDS) and hand length SDS were significantly higher in NSD1+/- patients.Conclusion: Arm span for height and hand length are discriminating parameters between NSD1+/- and NSD1+/+. [ABSTRACT FROM AUTHOR]