Sotos and Malan Syndromes in Childhood: Molecular and Clinical Findings From a Nationwide Cohort of 48 Patients
CLINICAL GENETICS, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1111/cge.70225
- Dergi Adı: CLINICAL GENETICS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Dokuz Eylül Üniversitesi Adresli: Evet
Özet
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 T & uuml;rkiye. 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 T & uuml;rkiye and supports improved diagnostic and clinical management strategies.