Mild Neurodevelopmental Disorder Due to SHMT2 Mutations: Expanding the Phenotypic Spectrum

Abstract Biallelic mutations in SHMT2 cause neurodevelopmental disorders with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB; OMIM: 619121). This recently described metabolic disorder are characterized by severe intellectual disability, microcephaly, spastic paraplegia, peripheral neuropathy, corpus callosum dysgenesis, facial and limb deformities, and progressive hypertrophic cardiomyopathy. Herein we describe the clinical characteristics of a patient with novel compound heterozygous SHMT2 missense variants (c. 1274G > A: p.R425Q and c.1042C > T: p.R348W), presenting with mild intellectual disability, corpus callosum dysgenesis, and speech delay. Different from previous cases, our patient represents the mildest phenotype reported to date, and expand the phenotypic spectrum of disease associated with SHMT2 mutation.