ClinVar

In a patient with severe epilepsy, Zsurka et al. (2010) identified a homoplasmic 616T-C transition in the MTTF gene in a highly conserved position in the anticodon stem. She had her first epileptic seizure at age 10 months, with a left-sided complex partial seizure followed by a transient paresis of the left arm. At age 2 years she had status epilepticus with bilateral myoclonus. She continued to have drug-resistant seizures, with myoclonus, complex partial seizures, and episodes of status epilepticus and epilepsia partialis continua. She also had chronic renal insufficiency and delayed psychomotor development. She died of heart failure after status epilepticus at the age of 17 years. There was no evidence of cerebellar ataxia, polyneuropathy, myopathy, or visual or hearing loss. A maternal cousin also had epileptic seizures starting in early childhood and died of kidney failure. Skeletal muscle biopsy of the proband did not show ragged red fibers, but did show a combined respiratory chain defect with reduced complex IV activity. Family members who were heteroplasmic for the mutation had no clinical symptoms.