Abstracts

Rationale: The objective of this presentation is to get better understanding of until now described electro-clinical spectrum of epilepsy in patients with chromodomain helicase DNA-binding protein 2 (CDH2) mutation. We present and describe the epileptic syndromes observed in four patients admitted in our centre with CHD2 mutations.CHD2 plays an important role in development of inhibitory and excitatory neurons however, it is still unknown how mutations in chromatin remodeler CHD2 contribute to impaired brain function in humans (Front Mol Neurosci 2018; 11;1-11). Recently, this mutation has been related to aberrant cortical network development and impaired memory in mice.Regarding to recent studies, CHD2 mutations seem to be responsible for developmental epilepsy encephalopathy in humans with a broad phenotype that can be characterized by infantile-onset generalized epilepsy, intellectual disability, photosensitivity (Seizure 2018; 57;8-10) and in some patients, atonic-myoclonic seizures (Epilepsy Behav 2015;51;53-56). This mutation has even been detected in Lennox Gastaut Syndrome (Epilepsy Behav 2014; 33;18-21) and in Dravet-syndrome affected patients without SCNA mutation (Epilepsia 2017; 58(11);1807-16). On the other hand, some reports describe psychoses phenomena in some patients with certain CHD2 mutations (Neuropsychiatr Dis Treat 2016;10;12:1135-9).In terms of developmental delay, moderate to severe intellectual disability, short-term memory problems, visual perception disability and short attention spam have been described and in some cases, behavioral disorders and less frequently autistic spectrum disorders (AED) (J Neurodev Disord 2014; 6;9)(Seizure 2017; 51;186-9).  Methods: We include four patients admitted in our center since 2016, with positive mutation detection in oriented exome analysis in CHD2 protein genes.All of them underwent structural MRI studies, prolonged v-EEG recordings, metabolic tests and oriented exome analysis. Two of them also underwent detailed neuropsychological and psychiatric evaluations.  Results: Our small series include 1 woman and 3 men. Three of them have been diagnosed with the mutation in the second decade of life although all patients presented seizures since age 3.Patients related different type of seizures; dialeptic with very unusual generalized tonic-clonic seizures, photosensitive self-induced myoclonic events and drop attacks probably related to myoclonic-atonic seizures.In terms of neurodevelopment delay, two of them presented moderate to severe impairment regarding epileptic encephalopathy. The other two patients presented less sever cognitive decline; one of them showed mixed prefrontal syndrome pattern in neuropsychological evaluation and the other one presented AED.The patients who suffered from moderate to severe psychomotor impairment, referred very frequent refractory myoclonic seizures with or without drop attacks and just eventual absence seizures. Patients with mild cognitive impairment suffered mainly from well-controlled absence seizures and just occasionally generalized tonic-clonic seizures and distinctively AED or psychotic phenomena in the course of the disease.Background cerebral activity impairment did not show an unequivocal correlation with seizure type, frequency or cognitive impairment; we could see patients with high seizure frequency and moderate cognitive delay and almost normal background frequencies and also patients with unusual absence seizures and AED and moderate background slowing hardly related with drugs or other coexisting factors.Intercital EEG findings included regular generalized 3Hz spike-wave discharges with normal background, irregular generalized spike and polispike discharges less than 2.5Hz and even paroxysmal generalized fast activity, the last two essentially in patients with myoclonic and myoclonic/tonic seizures and moderate to severe cognitively impairment. In contrast to previously reported cases, only one out of our four patients presented photoparoxysmal response with fixation-off phenomena.Patients who underwent neuropsychological evaluation, showed impaired attention and working memory and planning deficits suggesting mainly mixed prefrontal syndrome.  Conclusions: After analyzing our small series of patients with CDH2 mutation we could find a correlation between seizure type, seizure frequency and developmental delay. Patients with mild to moderate cognitive impairment mostly showed just unusual absence seizures but distinctively associated autistic spectrum disease or positive psychotic manifestations.We consider a remarkable finding the partial preservation of normal EEG background activity in some patients regarding Lennox-Gastaut Syndrome electro-clinical spectrum with more frequent and severe seizures and moderate to severe cognitive impairment and in contrast, moderate to severe slowing in patients with better controlled seizures and less cognitive impairment. Perhaps, these somehow unexpected findings should make us consider genetically determined epileptic syndromes in certain group of patients. Taking these findings into account we can conclude that we must suspect CHD2 mutation not just in epileptic encephalopathies with associated photoparoxysmal reponse, Dravet-syndrome affected patients without SCNA1 mutation but also in patients presenting Lennox Gastaut electro-clinical syndrome with somehow preserved background activity or in patients with well-controlled absence seizures with normal or not, EEG background presenting associates psychotic symptoms or autistic regression in the course of the disease.  Funding: No funding