Epilepsy with myoclonic-atonic seizures - genetic aetiologies, outcomes and prognostic indicators

Sep 30, 2026

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Epilepsy with myoclonic-atonic seizures, formerly myoclonic-astatic epilepsy or Doose syndrome, accounts for 1–2.2% of childhood-onset epilepsies. A cohort of 60 patients was followed between 1986 and 2024 to define genetic determinants, long-term clinical outcomes, and prognostic indicators using homogeneous inclusion criteria and next-generation sequencing. Myoclonic-atonic seizures predominated, and valproate, ethosuximide, benzodiazepines, and phenobarbital were most effective. Outcomes varied: 61.7% achieved seizure freedom, 38.3% had drug resistance, and 58.3% developed intellectual disability. Pathogenic variants were found in 38.5%, with exome sequencing yielding higher diagnostic rates. Prompt overall neurodevelopmental assessment at onset and prioritization of whole exome sequencing were supported by the results.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Methods and cohort description

Inclusion criteria and follow-up

Clinical, EEG, neuroimaging, neuropsychological and genetic analyses

Results

Seizure types and treatment response

Long-term outcomes and comorbidities

Prognostic factors

Genetic findings and diagnostic yield

[https://doi.org/10.1093/braincomms/fcaf507](https://doi.org/10.1093/braincomms/fcaf507) BRAIN COMMUNICATIONS 2026: fcaf507 | 1 BRAIN COMMUNICATIONS Epilepsy with myoclonic-atonic seizures: genetic aetiologies, outcomes and prognostic indicators Simona Pellacani, 1,2,† Simona Balestrini, 1,2,3,† Edoardo Fino, 1,2 Carmen Barba, 1,2 Mara Cavallin, 1 Tiziana Pisano, 1 Elena Parrini, 1 Anna Rita Ferrari,4 Chiara Marzi,5 Laura Grisotto6 and Renzo Guerrini 1,2 † These authors contributed equally to this work. Epilepsy with myoclonic-atonic seizures, formerly myoclonic-astatic epilepsy or Doose syndrome, accounts for 1–2.2% of childhoodonset epilepsies. We investigated genetic determinants, long-term clinical outcomes and prognostic indicators in a large cohort using homogeneous inclusion criteria. We studied 60 patients (26.7% female), mean age 14.5 years (±9.1, range 3.2–41), followed between 1986 and 2024 at two paediatric neurology centres. Average follow-up was 11.7 years. Inclusion criteria were seizure onset between 6 months and 8 years, generalized 2–6 Hz spike-wave discharges and video-EEG documented myoclonic-atonic, myoclonic seizures or both. We analysed clinical, EEG, neuroimaging, neuropsychological and genetic data obtained with next-generation sequencing. We used χ² test, t-test, Log-rank test, Cox regression, population-averaged logistic models and Benjamini–Yekutieli procedure to identify predictors of seizure outcome, intellectual disability and other neurodevelopmental comorbidities. We observed myoclonic-atonic seizures in 55/60 (91.7%), tonic-vibratory seizures in 44/60 (73.4%), absence seizures in 30/60 (50%), myoclonic seizures without postmyoclonic atonia in 25/60 (42%) and non-convulsive status epilepticus in 13/60 (21.7%) . A ‘stormy’ onset occurred in 26/60 patients (43.3%). The most effective drugs were valproate, ethosuximide, benzodiazepines and phenobarbital, used in different combinations, whereas the newer drugs offered no benefit. Long-term outcomes were variable. Thirty-seven patients (61.7%) achieved seizure freedom after 5.1 years on average. We observed drug resistance in 23/60 patients (38.3%) and intellectual disability in 35/60 (58.3%) . One adult patient died (mortality rate 1.80/1000-person-years) . Attention deficit hyperactivity disorder was the most common comorbidity (24/60, 40%) .‘Stormy’ onset did not predict a worse prognosis. Global developmental delay at epilepsy onset was associated with drug resistance (P = 0.004, Q = 0.064) and with intellectual disability (P = 0.003, Q = 0.048) . We found pathogenic variants in 15/39 (38.5%) patients undergoing next-generation sequencing, including four genes novel for this syndrome (KMT2E; POGZ; SHANK3; YWHAG), with exome sequencing yielding higher diagnostic rates than gene panels. Epilepsy with myoclonicatonic seizures is a complex syndrome with diverse genetic causes and variable seizure severity and outcomes. Our findings expand its genetic landscape and highlight the prognostic value of prompt overall neurodevelopmental assessment at clinical onset. Whole exome sequencing should be prioritized for early diagnosis and counselling. 1 Neuroscience and Human Genetics Department, Meyer Children’s Hospital IRCCS, Florence 50139, Italy 2 Neuroscience, Pharmacology and Child Health Department, University of Florence, Florence 50139, Italy 3 Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, WC1N 3BG London, UK 4 Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa 56128, Italy 5 Department of Statistics, Computer Science, Applications, University of Florence, Florence 50139, Italy 6 Department of Environmental and Prevention Sciences, University of Ferrara, Ferrara 44122, Italy Received May 02, 2025. Revised October 17, 2025. Accepted December 24, 2025. Advance access publication December 29, 2025 © The Author(s) 2025. Published by Oxford University Press on

FAQs

What patient population and follow-up duration were analyzed?

The study included 60 patients with seizure onset between 6 months and 8 years, followed between 1986 and 2024 at two paediatric neurology centres. The average follow-up was 11.7 years.

Which treatments were most effective for seizure control?

The most effective drugs were valproate, ethosuximide, benzodiazepines and phenobarbital, used in different combinations. Newer drugs did not provide added benefit in the cohort.

How did genetic testing influence diagnostic yield?

Pathogenic variants were identified in 15/39 patients undergoing next-generation sequencing. Exome sequencing produced higher diagnostic rates than gene panels, including four genes novel for this syndrome.

Sep 30, 2026

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