Homoplasmy of the m. 8993 T>G variant in a patient without MRI findings of Leigh syndrome, ataxia or retinal abnormalities

Abstract

Leigh syndrome is a progressive neurodegenerative syndrome caused by multiple mitochondrial DNA and nuclear DNA pathological variants. Patients with Leigh syndrome consistently have distinct brain lesions found on MRI scanning involving abnormal signal in the basal ganglia, brainstem and/or cerebellum. Other clinical findings vary depending on the genetic etiology and epigenetic factors. Mitochondrial DNA-derived Leigh syndrome phenotype is thought to be modulated by heteroplasmy level. The classic example is the clinical expression of the pathological variant, m. 8993 T>G. At heteroplasmy levels above 90%, the resulting phenotype is Leigh syndrome, but at levels 70–90% patients present with a syndrome of neuropathy, ataxia and retinitis pigmentosa. We describe a 15-year old girl with homoplasmic variant in m.8993 T>G and clinical and biochemical findings consistent with Leigh syndrome but with normal brain MRI findings and without retinal abnormalities or ataxia.