Expanding the Phenotype: A Case Report of a Novel Alanyl-tRNA Synthetase 2 (AARS2) Homozygous Mutation in a 17-Month-Old Child

TL;DR

A 17-month-old child with developmental delay and low muscle tone is found to have a new mutation in the AARS2 gene, which is now considered responsible for her symptoms.

Contribution

The paper reports a novel homozygous mutation in AARS2 associated with a new clinical phenotype in a young child.

Findings

AARS2 mutation initially labeled as variant of uncertain significance is now considered pathogenic.

The child's symptoms of developmental delay and hypotonia are linked to the AARS2 mutation.

Revisiting genetic variants with new clinical data can lead to updated diagnoses.

Abstract

Early developmental delay and progressive neurological symptoms are red flags when evaluating infants in neurology clinics. Early assessment and management are essential to improve outcomes, with genetic testing being a cornerstone. Even if initial genetic results were not suggestive, revisiting the reported variant and comparing it to the newly published reports of different phenotypes helps establish the clinical diagnosis, as the authors report in this case of a 17-month-old child who presented with global developmental delay and hypotonia and was found to have Alanyl-tRNA Synthetase 2 (AARS2) gene mutation that was deemed as variant of uncertain significance but now is believed to be pathogenic and responsible for her evolving clinical manifestations.

Figures