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Abstract
Background and Objectives The genetic developmental and epileptic encephalopathies (DEEs) comprise a large group of severe epilepsy syndromes, with a wide phenotypic spectrum. Currently, the rates of convulsive status epilepticus (CSE), nonconvulsive status epilepticus (NCSE), and sudden unexplained death in epilepsy (SUDEP) in these diseases are not well understood. We aimed to describe the proportions of patients with frequently observed genetic DEEs who developed CSE, NCSE, mortality, and SUDEP. Understanding the risks of these serious presentations in each genetic DEE will enable earlier diagnosis and appropriate management.
Methods In this retrospective analysis of patients with a genetic DEE, we estimated the proportions with CSE, NCSE, and SUDEP and the overall and SUDEP-specific mortality rates for each genetic diagnosis. We included patients with a pathogenic variant in the genes SCN1A, SCN2A, SCN8A, SYNGAP1, NEXMIF, CHD2, PCDH19, STXBP1, GRIN2A, KCNT1, and KCNQ2 and with Angelman syndrome (AS).
Results The cohort comprised 510 individuals with a genetic DEE, in whom we observed CSE in 47% and NCSE in 19%. The highest proportion of CSE occurred in patients with SCN1A-associated DEEs, including 181/203 (89%; 95% CI 84–93) patients with Dravet syndrome and 8/15 (53%; 95% CI 27–79) non-Dravet SCN1A-DEEs. CSE was also notable in patients with pathogenic variants in KCNT1 (6/10; 60%; 95% CI 26–88) and SCN2A (8/15; 53%; 95% CI 27–79). NCSE was common in patients with non-Dravet SCN1A-DEEs (8/15; 53%; 95% CI 27–79) and was notable in patients with CHD2-DEEs (6/14; 43%; 95% CI 18–71) and AS (6/19; 32%; 95% CI 13–57). There were 42/510 (8%) deaths among the cohort, producing a mortality rate of 6.1 per 1,000 person-years (95% CI 4.4–8.3). Cases of SUDEP accounted for 19/42 (48%) deaths. Four genes were associated with SUDEP: SCN1A, SCN2A, SCN8A, and STXBP1. The estimated SUDEP rate was 2.8 per 1,000 person-years (95% CI 1.6–4.3).
Discussion We showed that proportions of patients with CSE, NCSE, and SUDEP differ for commonly encountered genetic DEEs. The estimates for each genetic DEE studied will inform early diagnosis and management of status epilepticus and SUDEP and inform disease-specific counseling for patients and families in this high-risk group of conditions.
Glossary
- AS=
- Angelman syndrome;
- CSE=
- convulsive status epilepticus;
- DD=
- developmental delay;
- DEE=
- developmental and epileptic encephalopathy;
- DEE-SWAS=
- developmental and epileptic encephalopathy with spike and wave activation in sleep;
- DS=
- Dravet syndrome;
- EOAE=
- early-onset absence epilepsy;
- GTCS=
- generalized tonic-clonic seizure;
- EIDEE=
- early infantile DEE;
- EIMFS=
- epilepsy of infancy with migrating focal seizures;
- EM=
- eyelid myoclonus;
- EEM=
- epilepsy with eyelid myoclonus;
- EMA=
- epilepsy with myoclonic absence;
- EMAtS=
- epilepsy with myoclonic atonic seizures;
- EOAE=
- early-onset absence epilepsy;
- GEFS+=
- generalized epilepsy with febrile seizures plus;
- IESS=
- infantile epileptic spasms syndrome;
- IGE=
- idiopathic generalized epilepsy;
- IQR=
- interquartile range;
- JME=
- juvenile myoclonic epilepsy;
- LGS=
- Lennox-Gastaut syndrome;
- LKS=
- Landau-Kleffner syndrome;
- NCSE=
- nonconvulsive status epilepticus;
- SeLECTS=
- self-limited epilepsy with centrotemporal spikes;
- SUDEP=
- sudden unexplained death in epilepsy
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Barbara Jobst, MD, PhD, FAAN.
CME Course: NPub.org/cmelist
- Received August 6, 2022.
- Accepted in final form January 5, 2023.
- © 2023 American Academy of Neurology
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