The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.
A retrospective case note study of the aetiology and course of children in convulsive status epilepticus (CSE) admitted to a large paediatric intensive care unit (PICU) was undertaken between January 1999 and April 2004. Status epilepticus was defined as a prolonged (>30 min) tonic-clonic seizure irrespective of whether the seizure had stopped prior to admission to PICU. During this period, 137 (74 male) children aged 1 month to 15 years were admitted to PICU with 147 episodes of status epilepticus. Forty-seven of the 137 children (34%) were admitted following a prolonged febrile seizure. Thirty-eight of the 137 children (28%) had a remote symptomatic cause for the CSE, 24 (18%) were admitted for an acute symptomatic cause and 15 (11%) were admitted with an acute exacerbation of a pre-existing idiopathic/cryptogenic epilepsy. Six children had a progressive encephalopathy and no cause was identified in the remaining 7 of the 137 children (5%). Forty-nine (36%) of the 137 children had pre-existing epilepsy. The mean duration of CSE was 44 min. Forty-nine (36%) children admitted to PICU who had received a benzodiazepine with either phenobarbital or phenytoin, required further treatment to terminate the presenting episode of CSE. Forty-two of these 49 were treated with thiopentone anaesthesia and the remaining 7 with a continuous infusion of midazolam, successfully terminating status in all. No child died. Of the 70 children considered to be previously neurologically and developmentally normal prior to admission, only 1 child demonstrated a new gross neurological abnormality at the time of latest follow-up. Seven patients (5%) developed new or de novo epilepsy.
Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE). Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies. Results: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each. Significance: MAE is associated with significant neurodevelopmental impairment.MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity. K E Y W O R D S Doose syndrome, epilepsy/seizures, genetics, myoclonic astatic epilepsy SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section. How to cite this article: Tang S, Addis L, Smith A, et al; EuroEPINOMICS-RES Consortium. Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures. Epilepsia. 2020;61:995-1007. https://
Young people aged between 10 and 20 years will account for nearly 23% of the UK's total population by the end of 2012. This fact, coupled with an increasing number of children with chronic illness surviving into adulthood, means that the transition of children with chronic illness into adult care is becoming an increasingly important issue. Epilepsies are pervasive disorders that consist not only of recurrent epileptic seizures that can change over time, but also of evolving behavioural, academic and social difficulties. Many of these young individuals feel 'dumped' or 'left in the dark' once they are 'transferred' to adult care.
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