Homozygous Mutation in the QARS1 Gene Causing Developmental Epileptic Encephalopathy in Siblings in the Southeast Asian Region: An Interesting Case Report and Discussion.

Developmental epileptic encephalopathy (DEE) refers to conditions where cognitive functions are impacted both by seizures as well as interictal epileptiform activities and the neurobiological processes involved. They lead to early onset refractory epilepsy causing progressive decline in cerebral function, developmental delay, and significant EEG changes. Glutaminyl-tRNA synthetase (QARS) is encoded by the gene and its mutation has been implicated as one of the causes of DEE. We report two cases of siblings with mutation-associated DEE, severe global developmental delay, and microcephaly. The babies were born of a non-consanguineous marriage. All basic investigations and metabolic tests of both siblings were normal. Magnetic resonance imaging of the brain of both siblings showed loss of cerebral white matter. Electroencephalography showed multifocal epileptiform discharges in the left temporo-occipital and right frontal regions. Both siblings suffered from refractory epilepsy. Genetic tests and clinical exome sequencing revealed homozygous missense variation in exon 2 of the gene in both the siblings, and heterozygous states for their parents. There is a wide range of aetiologies for DEE with microcephaly, which have overlapping clinical presentations. With growing awareness and availability of genetic tests, it has become possible to do workups for complex neurological disorders. Establishing precise etiology helps in outlining the treatment (if available) and providing a prognosis to parents. It also plays a critical role in planning future pregnancies.