Reversal of Clinical Phenotype of Sotos Syndrome Due to Microduplication of NSD1 Gene

Indian J Pediatr. 2022 Nov;89(11):1137-1139. doi: 10.1007/s12098-022-04325-7. Epub 2022 Aug 4.

Abstract

Sotos syndrome is caused by heterozygous pathogenic variants or deletions in the long arm of chromosome 5 encompassing NSD1. The cardinal features of this condition are overgrowth, macrocephaly, and intellectual disability. Conversely, duplications leading to an extra copy of NSD1 result in a reverse phenotype that is observed in duplication/microduplication of the 5q region. An 11-y-old boy was referred to the genetics clinic in view of global developmental delay and general tonic-clonic seizures. Whole-exome sequencing revealed the presence of likely pathogenic copy number variation, a contiguous duplication of size ~4.11 Mb spanning genomic location chr5: g.(?_171773956)_(175880045_?)dup. After validation by multiplex ligation-dependent probe amplification (MLPA) and phenotypic correlation, a diagnosis of reverse Sotos syndrome was confirmed. As far as the authors know, this is the first patient report of reverse Sotos syndrome from India. It highlights the peculiar presentation of this disorder as well as discusses the increasing potential of exome sequencing to screen for copy number variations (CNVs).

Keywords: Microarray; Microdeletion; Microduplication; Multiplex ligation-dependent probe amplification; Sotos syndrome; Whole-exome sequencing.

MeSH terms

  • DNA Copy Number Variations
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Nuclear Proteins / genetics
  • Phenotype
  • Sotos Syndrome* / diagnosis
  • Sotos Syndrome* / genetics

Substances

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