“Twitching” and Stiffness in POLG1 Mutation Carriers: Red Flag or Red Herring?

Mutations in the POLG1 gene are the cause of a variety of disorders and syndromes, including, for instance, autosomal-recessive disorders such as the mitochondrial DNA depletion syndrome 4a, Alpers type (MTDPS4A; OMIM203700), as well as autosomaldominant disorders such as progressive external ophthalmoplegia (OMIM203700). Patients with an isolated and distinct phenotype as well as overlapping syndromes with alternating combinations of generalized myopathy, hearing impairment, neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataract have been reported. Myoclonus can also be part of the spectrum of POLG mutation carriers and is typically considered a red flag for mitochondrial disorders. The typical description of “twitching” by affected patients is, as a corollary, often associated with myoclonus. Here, we report 2 patients (father and son) with the POLG1 mutation in whom misinterpretation of “twitching” caused a delay in the diagnosis of a treatable medical condition potentially causing significant problems.