Epilepsy is an important feature of KBG syndrome associated with poorer developmental outcome

Nathan Buijsse, Floor E Jansen, Charlotte W Ockeloen, Marjan J A van Kempen, Shimriet Zeidler, Marjolein H Willemsen, Emanuela Scarano, Sonia Monticone, Evelien Zonneveld-Huijssoon, Karen J Low, Allan Bayat, Sanjay M Sisodiya, Debopam Samanta, Gaetan Lesca, Danielle de Jong, Jaqcues C Giltay, Nienke E Verbeek, Tjitske Kleefstra, Eva H Brilstra, Danique R M Vlaskamp*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)

Abstract

OBJECTIVE: To describe the epilepsy phenotype in a large international cohort of patients with KBG syndrome and to study a possible genotype-phenotype correlation.

METHODS: We collected data of patients with ANKRD11 variants by contacting University Medical Centers in the Netherlands, an international network of collaborating clinicians, and study groups who previously published about KBG syndrome. All patients with a likely pathogenic or pathogenic ANKRD11 variant were included in our patient cohort and categorized into an 'epilepsy group' or 'non-epilepsy group'. Additionally, we included previously reported patients with (likely) pathogenic ANKRD11 variants and epilepsy from the literature.

RESULTS: We included 75 patients with KBG syndrome of whom 26 had epilepsy. Those with epilepsy more often had moderate to severe intellectual disability (42.3% vs 9.1% , RR 4.6 (95% CI 1.7-13.1)). Seizure onset in patients with KBG syndrome occurred at a median age of four years (range 12 months - 20 years) and the majority had generalized onset seizures (57.7%)with tonic-clonic seizures being most common (23.1%). The epilepsy type was mostly classified as generalized (42.9%) or combined generalized and focal (42.9%), not fulfilling criteria of an electroclinical syndrome diagnosis. Half of the epilepsy patients (50.0%) were seizure free on anti-seizure medication (ASM) for at least one year at the time of last assessment, but 26.9% of patients had drug-resistant epilepsy (failure of ≥ 2 ASM). No genotype-phenotype correlation could be identified for the presence of epilepsy or epilepsy characteristics.

SIGNIFICANCE: Epilepsy in KBG syndrome most often presents as a generalized or combined focal and generalized type. No distinctive epilepsy syndrome could be identified. Patients with KBG syndrome and epilepsy had a significant poorer neurodevelopmental outcome compared to those without epilepsy. Clinicians should consider KBG syndrome as a causal etiology of epilepsy and be aware of the poorer neurodevelopmental outcome in individuals with epilepsy.

Original languageEnglish
Pages (from-to)1300-1313
Number of pages14
JournalEpilepsia Open
Volume8
Issue number4
Early online date27 Jul 2023
DOIs
Publication statusE-pub ahead of print - 27 Jul 2023

Bibliographical note

Funding Information:
This research received no specific grant from any funding agency. S.Sisodiya was supported by the Epilepsy Society.

Publisher Copyright:
© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Keywords

  • ANKRD11 gene
  • genotype–phenotype correlation
  • neurodevelopment
  • seizure

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