The Association of Scoliosis and NSD1 Gene Deletion in Sotos Syndrome Patients

Abstract

Study Design. A retrospective comparative study.Objective. The aim of this study was to examine the NSD1 abnormalities in patients diagnosed with Sotos syndrome and its correlation with the presence, severity, and progression of associated scoliosis. Summary of Background Data. Scoliosis has been reported in approximately 30% of patients diagnosed with Sotos syndrome, a genetic disorder characterized by a distinctive facial appearance, learning disability, and overgrowth. Sotos syndrome is mainly attributed to NSD1 haploinsufficiency, but with ethnical differences in genetic profile: NSD1 microdeletions are frequently identified in Japanese Sotos patients whereas intragenic mutations are more frequently found in non-Japanese patients. Although possible genotype-phenotype correlations have been proposed, the genotype of Sotos syndrome patients suffering from scoliosis has not been examined. Methods. The medical records and spinal radiographs of 63 consecutive Sotos syndrome patients at a single center were reviewed. Fluorescent in situ hybridization or microarray comparative genomic hybridization and DNA sequencing or multiplex ligation-dependent probe amplification were performed to detect 5q35 microdeletion involving the NSD1 gene and intragenic mutations of the NSD1 gene, respectively. The phenotypes of all cases and radiological assessments for the presence and progression of scoliosis were studied. Results. NSD1 abnormalities were identified in 55 patients (87%): microdeletion in 34 patients (54%) and intragenic mutation in 22 patients (33%). Scoliosis was observed in 26 patients (41%), with a significantly higher ratio of microdeletions than mutations. The 10 patients with progressive scoliosis all had NSD1 microdeletions. Conclusion. Scoliosis was a common phenotypical trait in children with Sotos syndrome and its presence as well as progression were higher in cases with NSD1 microdeletions. Although all Sotos syndrome patients should be monitored for scoliosis, clinicians should be made aware that patients with NSD1 microdeletions have a higher probability of scoliosis development and progression that may require early intervention.

Case Report of Neonatal Sotos Syndrome with a New Missense Mutation in the NSD1 Gene and Literature Analysis in the Chinese Han Population

“…For children with mental and motor retardation, rehabilitation assessment and treatment should be carried out at the earliest opportunity. Approximately 30% of patients with Sotos syndrome may develop scoliosis [ 16 ]; a follow-up system should thus be established, and timely treatment should be given to those with the relevant symptoms. Further, growth and development indicators should be evaluated during follow-up; in particular, for patients with abnormal cranial MRI, EEG, hearing, cardiac, urinary, and digestive system examinations, the follow-up interval should be shortened as necessary.…”

Atypical Sotos syndrome caused by a novel splice site variant

“…Scoliosis is also a major clinical finding, present in more than one-third of patients with Sotos syndrome 1 . Scoliosis is rarely aggravated in patients with Sotos syndrome; the presence of progressive scoliosis is associated with 5q35 microdeletions 4 . Here, we describe a patient with atypical Sotos syndrome caused by an intragenic mutation of NSD1 , a novel splice site variant.…”