Expanding the Genotypic Spectrum of SLC18A2 Mutation–Related Disorder—A Novel Mutation and Review of Literature

Abstract

Brain monoamine vesicular transporter deficiency is a rare autosomal recessive neurometabolic disorder caused by mutations in the SLC18A2 gene, which encodes vesicular monoamine transporter 2 (VMAT2). VMAT2 is essential for packaging neurotransmitters such as dopamine, serotonin, norepinephrine, and histamine into synaptic vesicles. Its deficiency results in disrupted neurotransmission and a characteristic clinical syndrome involving developmental delay, hypotonia, movement disorders, and autonomic dysfunction. We report a novel homozygous frameshift variant, Chr10:119014792dupC (p.Phe238LeufsTer7), identified in a 5-month-old male from a consanguineous family, who presented with severe hypotonia, oculogyric crises, and developmental delay. This variant expands the known genotypic spectrum of SLC18A2-related disease. Our findings underscore the importance of early genetic testing in infants with unexplained movement disorders and support a multidisciplinary approach to care. We also compare this case to related neurometabolic disorders with overlapping clinical features and with prior SLC18A2 mutation-related disorder.