Sotos Syndrome

Abstract

Abstract Sotos syndrome (OMIM # 117550 ) is a childhood overgrowth syndrome with distinctive craniofacial features and mental retardation. Sotos syndrome is caused by haploinsufficiency of the nuclear receptor SET domain containing protein 1 gene ( NSD1 ) located at 5q35.2‐q35.3. A wide variety of NSD1 aberrations have been found: microdeletions, intragenic deletions and missense and truncation mutations. Through in‐depth analyses of microdeletions, low copy repeat (LCR) or Alu ‐mediated rearrangements were demonstrated to be major mechanisms for de novo deletions. Therefore, Sotos syndrome is now considered as a genomic disorder. NSD1 is a protein with histone methyltransferase activity and nuclear receptor‐binding capability, both related to transcriptional controls. As pathophysiology regarding abnormalities of NSD1 protein remains unknown, further functional studies are necessary. Key concepts Haploinsufficiency of NSD1 causes Sotos syndrome. Sotos syndrome is a genomic disorder. Microdeletion involving NSD1 occurs through nonallelic homologous recombination mediated by low copy repeats or Alu elements. NSD1 has specific histone methyltransferase activity.