A clue for familial mitochondrial disorder: Discovering a vintage painting

A 73-year-old man presented with decades of slowly progressive bilateral ptosis and hearing loss. He also had peripheral polyneuropathy, intermittent binocular diplopia, and mild dysphagia and dysarthria. His mother and maternal grandmother had similar symptoms. He later discovered a vintage painting of his maternal great-grandfather (figure), which showed marked ptosis, disconjugate gaze, and facial weakness. Autosomal and maternal mitochondrial genome sequencing from blood revealed likely pathogenic heterozygous mutations at C10ORF2:c1366C > G (p.Leu456Val). The patient was diagnosed with autosomal dominant progressive external ophthalmoplegia, which can be associated with missense mutation of the C10orf2 gene encoding mitochondrial DNA helicase.1