[Variability of the clinical expression of KCNB1 encephalopathy]

The KCNB1 gene encodes a voltage-dependent potassium channel that regulates transmembrane currents in pyramidal neurons. Heterozygous variants have recently been associated with early-onset epileptic encephalopathies and intellectual disability, but their clinical characterisation has not yet been fully defined.

To describe the clinical spectrum associated with variants of KCNB1 in paediatric patients.

Retrospective study of four patients from three families with KCNB1 encephalopathy, including an analysis of the clinical and electroencephalographic features of epilepsy, associated neurological manifestations and neurodevelopmental pattern.

In two of them, the mutation in KCNB1 was de novo; the other two, who were sisters, inherited the variant from a parent with germline mosaicism. All had mild-to-moderate intellectual disability, two patients had autistic spectrum disorder and two had attention deficit hyperactivity disorder. Only case 2 displayed alterations in the MRI brain scan: progressive cortical atrophy. Three of them developed epilepsy (cases 1-3). Case 1: onset at 9.5 months with West syndrome that was well controlled with vigabatrine and zonisamide. Case 2: onset at 13 months with West syndrome, evolutionary development of polymorphic seizures (atonic, hypermotor, dysautonomic and tonic) that were refractory to 10 antiepileptic drugs and corticosteroids. Accompanied by a movement disorder characterised by ataxia, dyskinesias and tremor. Case 3: onset at 14.5 years with atonic seizures, multifocal EEG pattern and adequate control with levetiracetam.

KCNB1 encephalopathy has a heterogeneous natural history, mainly with respect to epilepsy, ranging from patients with refractory epilepsy to patients without any epileptic seizures. All had neurodevelopmental disorders, such as intellectual disability or autism spectrum disorder, independent of epilepsy.