The clinical and genetic spectrum in infants with (an) unprovoked cluster(s) of focal seizures

Background: Self-limited (familial) infantile epilepsy (S(F)IE), formerly known as benign (familial) infantile convulsions (13(F)1C), is an infantile cluster epilepsy with in rule a complete recovery. This form of epilepsy is most often caused by variations in the PRRT2 gene (OMIM #605751). Aim: To describe the clinical and genetic spectrum of sudden onset clusters of focal seizures in infancy. Methods: We retrospectively reviewed all individuals, who presented with unprovoked infantile seizures and selected all infants who had unprovoked clustered focal seizures between 1 and 20 months of age. We described the clinical and genetic spectrum of this cohort. Results: The data of 23 patients from 21 families were collected. All had an initial diagnosis of S(F)IE which was adjusted in 5 individuals. In 12 individuals a pathogenic variation in PRRT2 gene or complete deletion was identified. Pathogenic variants in PCDHI9 and KCNQ2 were found in respectively 3 and 1 individuals. One individual had a non-pathogenic variant in ATP1A3 and in 6 others no variants were identified. The mean cluster duration was 2.9 days (range 1-13) (see Table 1). Twelve infants had only one cluster. All patients had focal motor or non-motor seizures, in 12 (52%) followed by bilateral (tonic) clonic seizures. Positive family history was present in 74% of individuals. In 11/12 (92%) tested families, >= 1 family member carried the pathogenic PRRT2 variant. Age of seizure onset (ASO) averaged 6.2 months (range 2-20 months). Age of latest seizure averaged 16 months (range 2-92). In several interictal EEG (electroencephalogram) recordings multifocal spikes or spike-wave abnormalities were detected. Ictal EEG recordings detected primary focal abnormalities. Conclusion: We described 23 individuals with unprovoked cluster(s) of focal seizures at infancy. It appears to be a heterogeneous group. Half of them had a pathogenic variation in PRRT2 gene. Most had only one cluster of seizures. When clusters reoccur frequently, when seizures are more therapy-resistant and when seizures persist beyond the age of 2 years, another diagnosis or causative gene is likely. (C) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Jaar van publicatie:2020

Trefwoorden:A1 Journal article

BOF-keylabel:ja

BOF-publication weight:1

CSS-citation score:1

Authors from:Government

Toegankelijkheid:Closed