KARS1-Related Infantile-Onset Progressive Leukoencephalopathy With or Without Deafness: A Novel Variant and Phenotypic Expansion.
Javad Behroozi, Mehdi Khorrami, Arezoo Farhadi et al.
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Case in brief
A two-year-old Iranian boy born to non-consanguineous parents presented with developmental delay, seizures, and sensorineural hearing loss. Brain imaging showed leukoencephalopathy, consistent with infantile-onset progressive leukoencephalopathy (LEPID). Whole-exome sequencing identified compound heterozygous KARS1 variants, c.959G>A (p.Arg320His) and c.2T>C (p.Met1Thr); both were classified as likely pathogenic, and the latter was novel. The child also had synophrys, a pointed triangular chin, pulmonary stenosis, and an atrial septal defect. The report describes the genetic diagnosis and expanded phenotype; the abstract does not report a clinical resolution.
What made this case unusual
The combination of LEPID with dysmorphic facial features not previously reported in the reviewed cases, plus cardiac anomalies, broadened the described phenotype. One of the two compound heterozygous KARS1 variants was novel.
Diagnostic / clinical pearl
In a child with developmental delay, seizures, hearing loss, and leukoencephalopathy, KARS1-related disease remains a diagnostic consideration even when the parents are non-consanguineous; whole-exome sequencing identified the variants in this case.
Why it matters
The case supports considering craniofacial and cardiac findings within the reported KARS1-related phenotype, while the authors note that functional studies are needed to clarify these associations.