Two male siblings ages 15 and 10 yr old had similar features of intellectual disability, developmental delay, severe speech impairment, microcephaly, prematurity, and transient elevation of liver enzymes in infancy. Exome sequencing revealed one novel (c.65C>A; p.Ala22Asp) and one ultra-rare (c.3214T>C; p.Phe1072Leu) predicted damaging missense variant in trans in the gene encoding cytoplasmic valyl-tRNA synthetase (VARS). Biallelic variants in VARS have previously been associated with a neurodevelopmental disorder characterized by microcephaly, seizures, and cortical atrophy (NDMSCA; MIM #617802). Although our patients have no history of seizures or cortical atrophy, we suggest that the biallelic variants in VARS p.Ala22Asp and p.Phe1072Leu in this family are likely pathogenic and associated with NDMSCA, expanding the clinical phenotype of the condition.
Keywords: absent speech; appendicular hypotonia; intellectual disability, moderate; microcephaly; premature birth following premature rupture of fetal membranes.
© 2018 Okur et al.; Published by Cold Spring Harbor Laboratory Press.