Stroke and Stroke-Like Symptoms in Patients with Mutations in the POLG1 Gene

Introduction/Methods Mutations in POLG1, the gene encoding mitochondrial polymerase gamma (Polγ), have been associated with a number of well-characterized phenotypes. In this study, we report two cases of patients with biallelic POLG1 mutations and stroke. We also performed a review of the literature and report on all clinical studies of patients with POLG1 mutations in which stroke was described in the phenotype. For each patient, genotype and phenotype are reported. Results Including our two patients, a total of 22 patients have been reported with POLG1 mutations and stroke. The average age of onset of stroke in these patients was 9 years with a range of 1-23 years. In cases where localization was reported, the occipital lobes were the primary location of the infarct. Mutations in the linker-linker or linker-polymerase domains were the most frequent genotype observed. Seizures (16/22) and hepatic dysfunction/failure (8/22) were the most commonly reported symptoms in the stroke cohort. Conclusion This article raises an underrecognized point that patients with POLG1 mutations may suffer a cerebrovascular accident at a young age. The most common location of the infarction is in the occipital lobe. The presentation may be similar to MELAS and can be misdiagnosed as a migrainous stroke.