Neonatal Sotos Syndrome: A Novel Frameshift Mutation of the NSD1 Gene Associated with Neonatal Encephalopathy Presenting without Overgrowth

Abstract

Sotos syndrome type I is one of the more common genetic overgrowth disorders. It presents classically with macrocephaly, distinctive facial gestalt, and acromegalic features, along with neonatal complications including hypotonia, feeding difficulties, and hypoglycemia with other minor feature inconstancies. The phenotypical overlap of features of this syndrome, more so in neonatal age, thwarts an easy diagnosis. In this case report, a neonate of a nonconsanguineous marriage to a multigravida mother with insignificant obstetric history, presented primarily with respiratory difficulty, central hypotonia, and hypoglycemia. Sparse hair, tall forehead, pointed chin, and lax skin were accompanied by persistent encephalopathy and refractory myoclonic jerks. However, the quintessential features of pre- and postnatal overgrowth were lacking, making the line of diagnosis difficult. On neuroimaging, atypical diffuse pachygyria was found. Clinical exome sequencing revealed heterozygous single base pair deletion in exon 21 of the NSD1 gene on chromosome 5q35, resulting in an unreported frameshift and premature truncation of the protein 19 amino acids downstream to codon 2065, confirming the genetic diagnosis of autosomal dominant Sotos syndrome 1. The neonate later succumbed to death after withdrawal of ventilatory support.