Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C

• Published in: BMJ neurology open Vol. 3; no. 1; p. e000180
• Main Authors: Khoo, Anthony, Naidu, Saadnah, Wijayendran, Surapi Bhairavi, Merve, Ashirwad, Bremner, Fion, Sidhu, Meneka Kaur
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 16.06.2021; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Biopsy; botulinum toxin; Convulsions & seizures; Cytochrome; Dehydrogenases; Disease; Electroencephalography; Epilepsy; Family medical history; Histopathology; mitochondrial disorders; Mitochondrial DNA; Mutation; neurogenetics; Ostomy; Short Report; botulinum toxin; epilepsy; mitochondrial disorders; neurogenetics
• ISSN: 2632-6140; 2632-6140
• DOI: 10.1136/bmjno-2021-000180

IntroductionMitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy.SummaryWe report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing. This mutation, which affects the NADH dehydrogenase 6 (ND6) subunit of the mitochondrial respiratory chain, is most commonly implicated in cases of infantile-onset Leigh syndrome, although a broader phenotypic spectrum including migraine with aura and progressive myoclonic epilepsy have been described. Serial MRI scans over a 2-year period demonstrated the interval development of bihemispheric stroke-like lesions. Giant somatosensory evoked potentials and short-duration myoclonic jerks with craniocaudal spread on surface electromyography were consistent with cortical myoclonus. Optical coherence tomography showed bilateral symmetric thinning of the nerve fibre layer in the papillomacular bundles.ConclusionWhole-genome sequencing can help to provide a definitive diagnosis for mitochondrial disease and should be considered in situations where clinical suspicion remains high despite normal genetic panels or muscle histopathology. Mitochondrial disease can present as adult-onset progressive myoclonic epilepsy, and bilateral optic neuropathies can be a striking feature of ND6 mitochondrial gene mutations. In our case, severe cortical myoclonus affecting speech and swallowing remained highly drug-resistant, however, symptomatic benefit was derived from targeted onabotulinum toxin A injections.