Striatal Variant of POLR3A: Report of Two Indian Cases

Mutations in POLR3A are associated with a diverse spectrum of phenotypes ranging from classic hypomyelination to spastic ataxia, extrapyramidal syndromes with striatal atrophy (with or without hypomyelination), and neonatal progeroid syndromes. The striatal form is characterized by distinctive clinical and radiological features, most notably extrapyramidal symptoms such as dystonia. We report two unrelated Indian children with global developmental delay, extrapyramidal features, ataxia, and speech abnormalities. The first was misdiagnosed as dyskinetic cerebral palsy secondary to neonatal hyperbilirubinemia; the second, as Leigh's-like syndrome. Neuroimaging revealed white matter changes and striatal involvement, sparing the globus pallidus. Whole-exome sequencing identified a pathogenic POLR3A variant in both. To conclude, in children presenting with extrapyramidal symptoms and striatal changes on MRI, POLR3A-related disorders should be considered as a differential.