Medical Student University of Cincinnati College of Medicine Cincinnati, Ohio
This abstract has been invited to present during the Better Patient Outcomes through Diversity Platform poster session
Rationale: Leber’s hereditary optic neuropathy (LHON) is a genetic mitochondrial disease that can result in vision loss, commonly in young males. Epilepsy is infrequent in LHON and there are few published twin studies. We report on a female monozygotic twin (JC) who developed LHON two years after focal epilepsy onset. Methods: Data were collected from medical records at the University of Cincinnati (UC), including ophthalmology, neurology, EEG, neuropsychology, and neuroimaging. JC provided written informed consent for this report. Results: JC is a 55-year old female monozygotic twin, who began experiencing frequent focal seizures in 2010 with staring and behavioral arrest. She was first evaluated in the UC neurology clinic in 2012. EEGs at that time showed left frontotemporal slow wave activity and epileptiform discharges. She was refractory to several anti-seizure medications.
By 2012, JC experienced acute onset of decreased vision in the right eye and saw a LHON specialist in ophthalmology (Jan 2013). Perimetry showed a 30-degree central scotoma in the right eye and a 20-degree central scotoma in the left. Idebenone and B12 were prescribed to slow LHON progression, but she became legally blind by December 2013. Genetic testing revealed that JC, her twin sister, brother, and mother are all positive for a LHON genetic marker. To date, her mother and sister show no clinical signs of LHON.
By 2019, two right temporal lobe seizures had been recorded. EEGs also showed early spread to the left temporal lobe and bitemporal independent interictal activity, indicating possible bitemporal independent epilepsy. MRI of the brain showed optic atrophy and neuropsychological evaluation revealed bilateral frontotemporal dysfunction. She has no epilepsy risk factors other than LHON.
Her medical history includes glaucoma (paternal), hypertension, anxiety, depression, and sleep disturbance. Her maternal family history includes macular degeneration and LHON. Her brother lost vision bilaterally from LHON at age 18. JC’s monozygotic twin has diabetes, hypertension, and glaucoma but no seizures or vision loss. JC and her twin have no known difference in trauma history and have lived in the same household their entire lives, so they have unusually similar environmental exposure. Conclusions: This case is a rare combination of LHON plus neurologic disease (focal epilepsy) in a female patient whose monozygotic twin is asymptomatic. LHON is linked to mitochondrial DNA mutations, with an expected maternal inheritance pattern without sex linkage. The case is consistent with other published theories that phenotypic expression requires mitochondrial mutation, X chromosome mutation and expression, and an epigenetic trigger. Published LHON triggers of smoking and alcohol were not present, and the shared environment with her asymptomatic sister rules out major environmental triggers. It is possible that the onset of her epilepsy before vision loss reflected an early marker of LHON expression. Alternatively, the epilepsy may have served as an epigenetic event that triggered expression of the underlying genetic disorder. Funding: Please list any funding that was received in support of this abstract.: None
