10.1111/acn.v9999.9999

Vollständiger Abstract

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Sotos syndrome is an overgrowth disorder caused by heterozygous NSD1 variants, partial-gene deletions, or 5q35 microdeletions. Malan syndrome, a phenotypically overlapping condition, results from haploinsufficiency of the NFIX gene due to either heterozygous chromosomal microdeletions involving the 19p13.2 region or heterozygous loss-of-function variants. This multicenter study aimed to characterize the clinical and molecular features of individuals with Sotos and Malan syndromes in Türkiye. We retrospectively analyzed clinical and molecular data from 48 individuals with genetically confirmed Sotos or Malan syndrome across 14 centers. Molecular analyses included whole-exome sequencing, clinical exome sequencing, targeted gene panels, multiplex ligation-dependent probe amplification, and chromosomal microarray analysis. Forty-two individuals were diagnosed with Sotos syndrome and six with Malan syndrome. All exhibited characteristic facial features, and 97.9% had developmental delay or intellectual disability. We identified a total of 38 NSD1 variants, of which 35 were classified as pathogenic or likely pathogenic and three as variants of uncertain significance; notably, 23 of these variants were novel. Three patients carried 5q35 microdeletions, and one had an intragenic deletion involving exons 10-11. Four distinct NFIX variants (two novel) were detected in five patients, and one carried a 19p13.13 deletion encompassing the entire gene. This nationwide study expands the genotype-phenotype spectrum of Sotos and Malan syndromes in Türkiye and supports improved diagnostic and clinical management strategies.

Abstract: PubMed · Datensatz