Genetic Causes Found In Some Children With Severe Epilepsy

What was studied

This hospital-based study looked at 136 children with developmental and epileptic encephalopathies (DEEs). These are severe epilepsy conditions that usually start early in life and are linked with developmental delay or regression. The children were seen in a pediatric neurology division between 2017 and 2021 and were followed for at least 24 months.

The researchers retrospectively reviewed medical records to examine electroclinical features and underlying causes. They looked at age at seizure onset, sex, causes such as genetic, structural, or metabolic conditions, and genetic test results. About half of the children were female, and the average age when seizures started was 9.4 months.

What they found

The study found that DEEs had several different causes in this group. A genetic cause was identified in 41 of 136 children (30.1%), a structural cause in 32 (23.5%), and a metabolic cause in 17 (12.5%). Among the children with a genetic etiology, 32 had a genetically solved diagnosis, including 28 with pathogenic or likely pathogenic single-gene variants and 4 with pathogenic copy number variants or chromosomal rearrangements. Eight more had phenotype-concordant variants of uncertain significance, and 1 had a clinical-only genetic diagnosis.

SCN1A was the most frequently affected gene. Among the children with genetic DEEs, the electroclinical phenotypes included EIDEE in 11, Dravet syndrome in 10, IESS in 6, EMAS in 2, LGS in 2, and 10 who could not be clearly placed into one syndrome. The authors also described several novel variants in disease-associated genes.

Limits of the evidence

This was a retrospective study, meaning the researchers looked back at existing records rather than following a planned study from the start.

It was also done at a single university hospital, so the results may not represent all children with DEEs. Some children had uncertain genetic findings, and not every child had a confirmed cause. Although the abstract says the study aimed to examine prognosis, it does not provide detailed outcome results in the abstract.

For families and caregivers

For families, this study shows that DEEs are not one single disorder. Children with similar seizure and EEG patterns may have different underlying causes, and genetic testing identified an explanation in some children. Knowing the cause may help doctors classify the epilepsy syndrome more accurately.

At the same time, this study does not show that every child will receive a clear genetic answer. Some children remained without a clear diagnosis, and some gene findings were uncertain. Families may take from this that careful syndrome diagnosis and genetic evaluation can be important parts of care, but results are not always straightforward.

What to watch next

Larger studies from more than one center, with clearer reporting of long-term outcomes, could help further describe prognosis across genetic and electroclinical DEE subtypes.

Terms in this summary

developmental and epileptic encephalopathies (DEEs)

A group of severe epilepsy disorders that usually begin early in life and are linked with developmental delay or regression.

electroclinical phenotype

The combination of seizure features and EEG findings used to describe an epilepsy syndrome.

etiology

The underlying cause of a disease.

SCN1A

A gene that is commonly associated with some epilepsy syndromes, including Dravet syndrome.

variant

A change in a gene's DNA sequence.

variant of uncertain significance

A gene change that has been found, but it is still unclear whether it causes disease.

copy number variant

A missing or extra piece of DNA that can affect how genes work.

Dravet syndrome

A severe epilepsy syndrome that usually starts in infancy and is often associated with SCN1A changes.