Epilepsy with Eyelid Myoclonia Associated with CHD2 Variants: Report of Two Cases
Hannah Padilla1, Elaine Wirrell2, Lily Wong-Kisiel3, Anthony Fine3, Brendan Lanpher3, Kelsey Smith3
1Mayo Clinic Alix School of Medicine, 2Mayo Clinic/Dept of Child Neurology, 3Mayo Clinic
Objective:
To describe two cases of epilepsy with eyelid myoclonia (EEM) in the setting of CHD2 gene mutations.
Background:
EEM, previously known as Jeavons syndrome, is a childhood onset epilepsy syndrome characterized by eyelid myoclonia, photosensitivity, and eyelid closure-induced EEG seizures or paroxysms. While considered a genetic generalized epilepsy syndrome, genetic mutations are only rarely identified in patient, including mutations in the CHD2 gene, which encodes the chromodomain DNA helicase binding protein 2.
Design/Methods:
A database of 133 patients with EEM was searched to identify patients with CHD2 mutations. Charts of patients identified were reviewed to describe clinical presentation and evolution.
Results:
Of 133 patients with EEM, 35 had genetic testing consisting of an epilepsy gene panel and/or whole exome or genome sequencing. Of these, two patients had mutations in CHD2. The first patient was a male with autism spectrum disorder (ASD), learning disability, and attention deficit disorder (ADHD). Episodes of eyelid myoclonia started around 6 years of age and generalized tonic-clonic seizure at 11 years of age. EEG showed generalized atypical spike and wave discharges after eye-closure associated with eyelid myoclonia and a photo paroxysmal response. Genetic testing revealed a de novo CHD2 mutation, c.2636C>T (p.A8779V) variant. Convulsive seizures are well-controlled on lamotrigine, but eyelid myoclonia continues. The second case was a female with a history of ADHD, and ASD, who had events of eyelid myoclonia several times a day at 6 years old. EEG was consistent with EEM. Genetic testing revealed a de novo CHD2 mutation, c.3734delA, p.Lys1245Asnfs*4 variant. She continues to have eyelid myoclonia daily despite trials of ethosuximide, lamotrigine, clobazam, and valproic acid.
Conclusions:
We describe two patients with CHD2 mutations associated with EEM, in addition to ADHD and ASD expanding on the literature. CHD2 mutations should be considered in patients presenting with EEM, especially when ADHD and ASD are present.