Abstracts

Rationale: De novo mutations in CHD2 cause a neurodevelopmental phenotype characterised by one or more of intellectual disability, autistic features and epileptic encephalopathy. We recently published a case series of ten individuals with de novo CHD2 mutations – one of whom had a small chromosomal deletion at 15q26.1 producing a very similar phenotype. We set out to: 1) confirm the phenotypic spectrum in a larger sample; 2) compare the characteristics of patients with genic mutations to those with relevant chromosomal deletions. Methods: We identified cases via the rare epilepsy syndromes network of EuroEpinomics, the DECIPHER database and through colleagues. Clinical data were collected including development, seizure type, psychiatric features, EEG, imaging, clinical photographs, psychometric tests and response to medication. Results: We report 30 new cases (17 are female). Thirteen had a genomic deletion. Developmental delay and Intellectual disability (ID) was recorded in 26 patients, but three were recorded as having normal intellect. 14 had mild ID, 5 moderate and 7 had severe ID. 29 had epilepsy, and photosensitivity was common, affecting at least 11 patients (two with a deletion, nine with genic mutations). 15 patients exhibited significant behavioural disturbance: 11 had autistic spectrum disorder, 7 patients with ADHD. 6 patients had significant mental health disorders including schizophrenia, depression, potomania and Tourette’s syndrome. Although the majority of the patients assessed were not dysmorphic, those who were shared common features including prominent eyebrows and upturned lips. Conclusions: This cohort confirms the description of the early-onset photosensitive myoclonic and absence seizure dominant epileptic encephalopathy. We also describe cases where the epilepsy was not as severe – and in some cases the autism of schizophrenia illnesses dominated. We present photographs with some common dysmorphic features that may aid clinical recognition. Funding: None