Electroclinical Features of Epilepsy in Kleefstra Syndrome

 

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Abstract

Background Kleefstra syndrome (KS) or 9q34.3 microdeletion syndrome (OMIM #610253) is a rare genetic condition featuring intellectual disability, hypotonia, and dysmorphic facial features. Autism spectrum disorder, severe language impairment, and sleep disorders have also been described. The syndrome can be either caused by a microdeletion in 9q34.3 or by pathogenic variants in the euchromatin histone methyltransferase 1 gene (EHMT1, *607001). Although epilepsy has been reported in 20 to 30% of subjects, a detailed description of epileptic features and underlying etiology is still lacking. The purpose of this study is to investigate epilepsy features in a cohort of epileptic patients with KS.

Methods This multicenter study investigated eight patients with KS and epilepsy. Our findings were compared with literature data.

Results We included five patients with 9q or 9q34.33 deletions, a subject with a complex translocation involving EHMT1, and two with pathogenic EHMT1 variants. All patients presented with moderate to severe developmental delay, language impairment, microcephaly, and infantile hypotonia. Although the epileptic manifestations were heterogeneous, most patients experienced focal seizures. The seizure frequency differs according to the age of epilepsy onset, with patients with early-onset epilepsy (before 36 months of age) presenting more frequent seizures. An overtime reduction in seizure frequency, as well as in antiseizure drug number, was observed in all patients. Developmental delay degree did not correlate with seizure onset and frequency or drug resistance.

Conclusion Epilepsy is a frequent finding in KS, but the underlying pathogenetic mechanism and specific features remain elusive.

Note

This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (law 232/2016). IRCCS Istituto Giannina Gaslini is a full member of ERN EpiCARE.

Data Availability Statement

The data that support the findings of this study are reported in the manuscript.

^* T.G. and R.C. contributed equally to this work.

Publication History

Received: 11 June 2023

Accepted: 12 September 2023

Article published online:
06 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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