Asymmetric Chronic Progressive External Ophthalmoplegia : Clinical and Genetic Insights

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial myopathy typically characterized by symmetric ptosis and ophthalmoplegia. However, asymmetric presentations have been increasingly recognized and may complicate diagnosis. We prospectively enrolled nine patients with pathologically and/or genetically confirmed CPEO. All patients underwent comprehensive neuro-ophthalmologic evaluation, and selected patients underwent muscle biopsy and molecular genetic analyses of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Clinical, radiological, pathological, and genetic findings were systematically analyzed. Six of nine patients (67%) presented with asymmetric ptosis and/or ophthalmoplegia, while three showed symmetric involvement. One patient evolved from an asymmetric to a symmetric phenotype during follow-up. Orbital MRI demonstrated variable patterns of extraocular muscle atrophy, including unilateral or diffuse involvement. Muscle biopsy confirmed mitochondrial myopathy in seven patients. Genetic analyses from muscle specimen identified mtDNA deletions in four patients and nDNA mutations in two, while two were diagnosed by detecting an mtDNA deletion in buccal mucosa without biopsy. All five genetically confirmed cases with asymmetrical CPEO harbored mtDNA deletions, whereas three symmetric cases were associated with either mtDNA deletions (n = 1) or nDNA mutations (n = 2). CPEO can frequently manifest with asymmetric ptosis and ophthalmoplegia, primarily associated with mtDNA deletions. Recognizing this clinical and genetic heterogeneity is essential for prompt diagnosis, appropriate genetic testing, and effective counseling of patients with chronic progressive ophthalmoplegia.