Adult phenotype of KCNQ2 encephalopathy.

Background: Pathogenic KCNQ2 variants are a frequent cause of developmental and epileptic encephalopathy.
Methods: We recruited 13 adults (between 18 years and 45 years of age) with KCNQ2 encephalopathy and reviewed their clinical, EEG, neuroimaging and treatment history.
Results: While most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood. The most common seizure type was tonic seizures (early) infancy, and tonic-clonic and focal impaired awareness seizures later in life. Ten individuals (77%) were seizure-free at last follow-up. In 38% of the individuals, earlier periods of seizure freedom lasting a minimum of 2 years followed by seizure recurrence had occurred. Of the 10 seizure-free patients, 4 were receiving a single antiseizure medication (ASM, carbamazepine, lamotrigine or levetiracetam), and 2 had stopped taking ASM. Intellectual disability (ID) ranged from mild to profound, with the majority (54%) of individuals in the severe category. At last contact, six individuals (46%) remained unable to walk independently, six (46%) had limb spasticity and four (31%) tetraparesis/tetraplegia. Six (46%) remained non-verbal, 10 (77%) had autistic features/autism, 4 (31%) exhibited aggressive behaviour and 4 (31%) destructive behaviour with self-injury. Four patients had visual problems, thought to be related to prematurity in one. Sleep problems were seen in six (46%) individuals.
Conclusion: Seizure frequency declines over the years and most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are common during childhood and adolescence. Most adult patients have severe ID. Motor, language and behavioural problems are an issue of continuous concern.
Competing Interests: Competing interests: EC is a consultant to Xenon Pharmaceuticals and Knopp Biosciences; his participation in this work has been reviewed and approved by Baylor College of Medicine in accordance with institutional conflict of interest policies. MKK serves on speakers bureaus for Greenwich, Novartis and Lundbeck, and on an advisory board for Stealth Biotherapeutics. PS received fees from Ultragenyx, Zogenyx, Biomarin, PTC pharmaceuticals, GW pharma, Neuraxpharma and research grants from GW pharma, PTC Pharmaceuticals, ENECTA SV, Kolfarma, and has been investigator for clinical trials for Ultragenyx and Zogenix. SW received speaker and consultancy fees from UCB, Xenon, Zogenix, Lundbeck and Biocodex.
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