New study from Italy on epilepsy in Kleefstra Syndrome

Epilepsy is known to occur in individuals with Kleefstra syndrome. For many years, however, most publications were limited to reporting epileptic seizures as just another potential feature of the syndrome, without examining them systematically. the type of seizures, the age of onset, the electroencephalogram findings, and their evolution with age.

In 2023, a team of researchers from Italy published in the scientific journal Pediatric neurology the study Electroclinical Features of Epilepsy in Kleefstra Syndrome, one of the few studies focusing specifically on the electroclinical phenotype of epilepsy in Kleefstra Syndrome.

The importance of the study was recognized later as well. In 2026 it was used as a bibliographic source in the first International Clinical Evidence-Based Guideline for Kleefstra Syndrome, particularly for data concerning the age of onset and the course of epileptic seizures.

A small but highly targeted study

The researchers studied eight individuals with Kleefstra syndrome and epilepsy.

Of these, five had a deletion in the 9q or 9q34.33 region, one individual had a complex chromosomal rearrangement affecting EHMT1, and two had pathogenic variants in the gene itself EHMT1. All presented moderate to severe developmental delay, language disorder, microcephaly, and infantile hypotonia.

The sample is clearly small and therefore the study cannot be used to calculate how common epilepsy is in all individuals with Kleefstra.

Its value lies elsewhere. The researchers tried to examine in greater depth the type and evolution of epilepsy in individuals who had already experienced seizures.

Epilepsy in Kleefstra does not have a single type

One of the main conclusions was the great heterogeneity of epileptic manifestations.

A specific type of seizure that characterizes all individuals with Kleefstra syndrome was not found. However, focal seizures were the most frequent in this specific group. Different types of seizures have also been described in the literature, supporting the picture of a broad rather than a single epileptic phenotype.

This is important because it shows that we should not expect a specific, «typical» type of epilepsy in all children or adults with Kleefstra.

In other words, the presence of different forms of seizures in different individuals is not necessarily unusual for the syndrome.

Seizures appear to decrease with age

However, the study also delivered a particularly interesting message regarding the long-term outlook.

In the patients who were followed up, it was recorded over time reduction of seizure frequency. At the same time, the number of antiepileptic drugs needed also decreased.

This finding is important, as it suggests that at least in some individuals with Kleefstra, epilepsy may show improvement as age increases.

However, it should not be interpreted as a prediction for every individual with the syndrome, nor as an indication that antiepileptic therapy can be discontinued without medical evaluation. The decision to reduce or discontinue antiepileptic treatment is individualized and must be made by the treating neurologist.

Developmental delay and severity of epilepsy

Another interesting result was that in the specific group The degree of developmental delay did not correlate with the age of onset of seizures, their frequency, or resistance to pharmacological treatment.

Practically speaking, this means that the severity of an individual's developmental profile does not appear to allow us to predict how severe their epilepsy will be.

And here, due to the very small number of participants, larger studies are required before definitive conclusions can be drawn.

The study does not yet give us a specific «Kleefstra epilepsy type.» Rather, it shows us the opposite. Epilepsy in Kleefstra syndrome appears to be heterogeneous. Focal seizures were frequent in the specific patient series, onset before three years of age was associated with more frequent seizures and, at the same time, a trend toward a decrease in both seizures and the need for antiepileptic drugs was observed with increasing age.