Pontine stroke in a patient with Chronic Progressive External Ophthalmoplegia (CPEO): A case report

Background: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease with slowly progressive bilateral ptosis and symmetric ophthalmoplegia due to a genetic mutation that results in defective oxidative phosphorylation. Common genes that are implicated in CPEO include POLG, RRM2B, ANT1 and PEO1/TWNK. Here, we report a case of a patient diagnosed with CPEO caused by a novel mutation in PEO/TWNK after suffering a right pontine stroke.

Case presentation: A 70-year-old man with history of chronic progressive bilateral ptosis and ophthalmoplegia, as well as similar ocular symptoms in his father and grandfather, presented with acute onset of right hemifacial weakness and dysarthria. Brain MRI revealed an acute ischemic stroke in the right dorsal pons. The patient did not experience diplopia due to severe baseline ophthalmoplegia. Creatine kinase was elevated to 6,080 U/L upon admission and normalized over the course of one week; electromyography revealed a myopathic process. Genetic testing revealed a novel mutation c.1510G > A (p. Ala504Thr) in a pathogenic "hot spot" of the C10ORF2 gene (TWNK/PEO1), which is associated with CPEO. The mutation appears to be deleterious using several pathogenicity prediction tools.

Conclusions: This case report describes a patient with late-onset CPEO caused by a novel, likely pathogenic, mutation in the TWNK gene. Although the patient presented with a pontine stroke, it manifested with solely new onset facial palsy, as he had a severe underlying ophthalmoplegia secondary to his CPEO.