CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures. (3rd March 2015)

• Record Type: Journal Article
• Authors: Thomas, Rhys H.; Zhang, Lin Mei; Carvill, Gemma L.; Archer, John S.; Heavin, Sinéad B.; Mandelstam, Simone A.; Craiu, Dana; Berkovic, Samuel F.; Gill, Deepak S.; Mefford, Heather C.; Scheffer, Ingrid E.
• Is Part Of: Neurology. Volume 84:Number 9(2015)
• Publication Date: 2015-03-03
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000001305
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To delineate the phenotype of early childhood epileptic encephalopathy due to de novo mutations of CHD 2, 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.