Milder Phenotype of Homoplasmic Versus Heteroplasmic m.8344A>G Variant in the Same Family: A Case Report

A myoclonic epilepsy with ragged-red fibers (MERRF) patient who carried the m.8344A>G variant in the homoplasmic form manifested a milder phenotype than his sister who carried the same variant in the heteroplasmic form, which has not yet been reported. The 27-year-old male, with an uneventful history, presented at age 19 with fatigue and persistent tremor in both hands. When he talked for a long time, his speech would slow down, and he would stutter. Although electroencephalography showed spike-wave complexes in both occipital projections with generalization, no anti-seizure drugs were given. At age 20, the patient suffered a fall due to muscle weakness. From age 21, generalized myocloni occurred. Because the sister had been diagnosed with MERRF-plus syndrome, the patient underwent genetic testing, which revealed the m.8344A>G variant in homoplasmy. L-carnitine was started. At age 27, the patient experienced a first “syncope” after a long walk, which subsequently recurred up to 2-3 times per day. EEG showed low-amplitude spikes, slow-spike waves at the posterior vertex, and generalized slow-spike waves. Clonazepam was recommended but declined by the patient. In conclusion, the m.8344A>G variant may manifest milder and with a later onset in the homoplasmic as compared to the heteroplasmic form. Further, the homoplasmy of the m.8344A>G variant appears to be more beneficial than harmful.