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Objective: The aim of this study was 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 on 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 4 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 the criteria of an electroclinical syndrome diagnosis. Half of the epilepsy patients (50.0%) were seizure free on anti-seizure medication (ASM) for at least 1 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 significantly poorer neurodevelopmental outcome compared with 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., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Intragenic mutations in FGF12 are associated with intractable seizures, developmental regression, intellectual disability, ataxia, hypotonia, and feeding difficulties. FGF12 duplications are rarely reported, but it was suggested that those might have a similar gain-of-function effect and lead to a more or less comparable phenotype. A favorable response to the sodium blocker phenytoin was reported in several cases, both in patients with an intragenic mutation and in patients with a duplication of FGF12 . We report three individuals from two families with FGF12 duplications. The duplications are flanked and probably mediated by two long interspersed nuclear elements (LINEs). The duplication cases show phenotypic overlap with the cases with intragenic mutations. Though the onset of epilepsy might be later, after the onset of seizures both groups show developmental stagnation and regression in several cases. This illustrates and further confirms that chromosomal FGF12 duplications and intragenic gain-of-function mutations yield overlapping phenotypes., Competing Interests: None of the authors has any conflict of interest to disclose. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© 2020 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.)

SCN8A encodes Nav1.6, one of the main voltage-gated sodium channel subunits in the brain, and SCN8A mutations lead to epileptic encephalopathy. Particular mutations render the mutant channel more susceptible to inhibition by phenytoin. Yet, the potentially severe side effects of phenytoin maintenance therapy, especially cognitive impairment, are undesirable in these already cognitively impaired patients. We describe a 5-year-old patient with SCN8A encephalopathy in whom phenytoin proved successful as emergency treatment to prevent clustering of seizures and status epilepticus, thus hospital stays. The ketogenic diet, levetiracetam, zonisamide, topiramate, and phenytoin maintenance therapy resulted in adverse reactions not previously documented in SCN8A encephalopathy.