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CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures
Rhys H Thomas1, Lin Mei Zhang1, Gemma L Carvill1
1From the Epilepsy Research Centre (R.H.T., L.M.Z., J.S.A., S.B.H., S.A.M., S.F.B., I.E.S.), University of Melbourne, Austin Health, Heidelberg, Australia; MRC Centre for Neuropsychiatric Genetics & Genomics (R.H.T.), Hadyn Ellis Building, Cathays, Cardiff University, UK; Department of Neurology (L.M.Z.), Children's Hospital of Fudan University, Shanghai, China; Department of Pediatrics (G.L.C., H.C.M.), Division of Genetic Medicine, University of Washington, Seattle; Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia; Departments of Radiology and Paediatrics (S.A.M., I.E.S.), Royal Children's Hospital, and University of Melbourne, Australia; Carol Davila University of Medicine (D.C.), Pediatric Neurology Clinic, Al Obregia Hospital, Bucharest, Romania; and TY Nelson Department of Neurology (D.S.G.), The Children's Hospital at Westmead, Sydney, Australia.
Objective:
To delineate the phenotype of early childhood epileptic encephalopathy due to de novo mutations of CHD2, which encodes the chromodomain helicase DNA binding protein 2.
Methods:
We analyzed the medical history, MRI, and video-EEG recordings of 9 individuals with de novo CHD2 mutations and one with a de novo 15q26 deletion encompassing CHD2.
Results:
Seizures began at a mean of 26 months (12-42) with myoclonic seizures in all 10 cases. Seven exhibited exquisite clinical photosensitivity; 6 self-induced with the television. Absence seizures occurred in 9 patients including typical (4), atypical (2), and absence seizures with eyelid myoclonias (4). Generalized tonic-clonic seizures occurred in 9 of 10 cases with a mean onset of 5.8 years. Convulsive and nonconvulsive status epilepticus were later features (6/10, mean onset 9 years). Tonic (40%) and atonic (30%) seizures also occurred. In 3 cases, an unusual seizure type, the atonic-myoclonic-absence was captured on video. A phenotypic spectrum was identified with 7 cases having moderate to severe intellectual disability and refractory seizures including tonic attacks. Their mean age at onset was 23 months. Three cases had a later age at onset (34 months) with relative preservation of intellect and an initial response to antiepileptic medication.
Conclusion:
The phenotypic spectrum of CHD2 encephalopathy has distinctive features of myoclonic epilepsy, marked clinical photosensitivity, atonic-myoclonic-absence, and intellectual disability ranging from mild to severe. Recognition of this genetic entity will permit earlier diagnosis and enable the development of targeted therapies.