Identification of a novel NSD1 pathogenic variant in a Senegalese child with Sotos syndrome

Sotos syndrome previously known as cerebral gigantism is a genetic disease characterized by excessive growth from the prenatal stage to childhood, accompanied with distinctive facial dysmorphism (broad and prominent forehead, hypertelorism, downward-slanting palpebral fissures, and a pointed chin), advanced bone age, macrocephaly, congenital malformations (heart defects, seizures, scoliosis, increased tumor susceptibility) and developmental delay (speech delay, learning disabilities, infantile hypotonia). Most cases of Sotos syndrome (90%) are linked to heterozygous mutations of the NSD1 gene. Here we reported the first case of Sotos syndrome from Senegal, confirmed by genetic testing. We detected a novel heterozygous mutation in exon 5 of the NSD1 gene in the index case, resulting in a frameshift and a premature stop codon (NM_022455): c.2306dup: (p.Gly771Trpfs*38). This mutation occured de novo in the index case and was not detected in either parent. Further studies are needed to explore genotype-phenotype correlations and potential targeted therapies.