Epidemiology of Developmental and Epileptic Encephalopathy and of Intellectual Disability and Epilepsy in Children

Abstract

Background and Objectives:We aimed to determine the population-based cumulative incidence and prevalence of developmental and epileptic encephalopathies (DEEs) and intellectual disability and epilepsy (ID+E) in children. We analyzed the cumulative incidence of specific epilepsy syndromes.Methods:Children under 16 years with a DEE or ID+E were ascertained using EEG records from 2000-2016 in the Wellington region of New Zealand. Epilepsy syndromes were diagnosed on medical record and EEG review. Point prevalence and cumulative incidence were calculated, and cumulative incidence for each epilepsy syndrome.Results:The cohort comprised 235 children (58% male) with developmental impairment and epilepsy, including 152 (65%) with DEE and 83 (35%) with ID+E. Median age of seizure onset was 15.4 months (range day 1 - 15 years). Median follow-up from seizure onset was 7.9 years (range 0-18.2 years). Point prevalence for the broad group of children with epilepsy and developmental impairment was 175/100,000 children (95% CI 149-203; DEE 112 and ID+E 63/100,000 children). Cumulative incidence for DEE was 169/100,000 children (CI 144-199) and for ID+E was 125/100,000 (CI 95.4-165). Cumulative incidence per 100,000 children was: infantile epileptic spasms syndrome 58.2 (CI 45.0-75.3), epilepsy with myoclonic-atonic seizures 16.4 (CI 9.69-27.7), Lennox-Gastaut syndrome 13.2 (CI 4.1-41.9), and Dravet syndrome 5.1 (CI 2.1-12.2). 50/152 (33%) of children with DEE and 70/83 (84%) with ID+E could not be diagnosed with a known epilepsy syndrome.Discussion:Epilepsy and developmental impairment prior to age 16 years occurs in 1 in 340 children, with 1 in 590 having a DEE and 1 in 800 ID+E. These individuals require significant health and community resources, therefore these data will inform complex health service and education planning. Epidemiological studies have focused on early childhood onset DEEs. These do not fully reflect the burden of these disorders as 27% of DEEs and 70% of ID+E begin later, with seizure onset after 3 years. Understanding the cumulative incidence of specific syndromes together with the broad group of DEEs is essential for planning of therapeutic trials. Given trials focus on specific syndromes there is a risk that effective therapies will not be developed for 1/3 of children with DEE.

Intellectual Disability and Epilepsy: The High Incidence and the Risks of Status Epilepticus and Sudden Death Require Improved Therapies

“…By virtue of a median clinical follow-up period of about 8 years, the authors also studied features including seizure-freedom rates, progression from epileptic spasms (ES) to other syndromes, differing severities of ID in patients with DEE and in children with IDþE, deaths, and the number of resolved epilepsy cases. 1 The authors found that the cumulative incidence of the combination of DEE and IDþE before age 16 years was quite large: 1 in 340 children. 1 Specifically, the incidence of DEE was 1 in 590 children through childhood and adolescence, which is more than double the incidence found in a Scottish study of DEE with onset before age 3 years.…”

“…1 The authors found that the cumulative incidence of the combination of DEE and IDþE before age 16 years was quite large: 1 in 340 children. 1 Specifically, the incidence of DEE was 1 in 590 children through childhood and adolescence, which is more than double the incidence found in a Scottish study of DEE with onset before age 3 years. 2 The cumulative incidence of IDþE was 1 in 800 children, and 70% of the latter cases had epilepsy onset between ages 3 and 15 years.…”

“…Not surprising to clinicians who care for ID patients with epilepsy, the authors determined that one-third of DEE patients (most of whom had a focal DEE) could not be classified into one of the current ILAE-defined syndromes. 1,3 Among the IDþE group, the majority had focal epilepsy also, and 84% could not be diagnosed with an ILAE syndrome. With respect to other features, the overall incidence of epilepsy was highest in the first year of life, the median ages of epilepsy onset were 9.0 and 46.5 months in the DEE and the IDþE children, respectively (P < .001), severe to profound ID occurred 3.7 times more often in children with a DEE than with IDþE, mortality was 13% in DEE and 11% in IDþE children, seizure-freedom for 5 years occurred in 27% of DEE and 59% of IDþE children (P ¼ .01), and epilepsy resolved in 15.6% of DEE and 48.1% of IDþE children.…”

“…With respect to other features, the overall incidence of epilepsy was highest in the first year of life, the median ages of epilepsy onset were 9.0 and 46.5 months in the DEE and the IDþE children, respectively (P < .001), severe to profound ID occurred 3.7 times more often in children with a DEE than with IDþE, mortality was 13% in DEE and 11% in IDþE children, seizure-freedom for 5 years occurred in 27% of DEE and 59% of IDþE children (P ¼ .01), and epilepsy resolved in 15.6% of DEE and 48.1% of IDþE children. 1 In the second article, the rates of convulsive status epilepticus (CSE), nonconvulsive status epilepticus (NCSE), overall mortality, and sudden unexpected death in epilepsy (SUDEP) were investigated in 510 DEE patients in an Australian genetic registry. 4 Although the rates of SE and SUDEP have been well described for Dravet syndrome, these data are less well defined for the more recently identified genetic DEEs.…”

Diagnostic Utility of Genome-wide DNA Methylation Analysis in Genetically Unsolved Developmental and Epileptic Encephalopathies and Refinement of a CHD2 Episignature

“…The developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies, defined by frequent epileptiform activity associated with developmental slowing or regression 1 . While each genetic etiology is rare, with more than 825 genes implicated 2 , the cumulative incidence of DEEs overall is 1 in 590 children 3 . Currently, de novo, X-linked, or recessively inherited pathogenic germline variants are found in ∼50% of individuals with DEEs who undergo genetic testing 4 .…”