Abstract
Objective: To characterize the range of clinical manifestations of KCNA2 mutation related epileptic encephalopathies.
Background: The KCNA2 gene codes for the Kv1.2 potassium channel, and mutations in this gene have been implicated in the development of epileptic encephalopathies. To our knowledge, there are only ten cases of KCNA2 related epileptic encephalopathies. The spectrum of presentation of these encephalopathies has not been fully defined. Here we report novel clinical characteristics in three previously unreported cases that expand the phenotype.
Design/Methods: Blood samples were sent for whole exome sequencing by GeneDx. Seizure types were characterized by clinical exam, history taking and EEG recording.
Results: Through whole exome sequencing we identified 3 patients with KCNA2 mutations. Patient 1 is a 5-year-old male with a c.1214 C>T (p.P405L) mutation, previously reported as a disease-associated mutation. In addition to experiencing several seizure types and multifocal areas of epileptogenic activity on EEG, Patient 1 was noted to have electrical status epilepticus of sleep, which has never been reported in patients with KCNA2 mutations. Patient 2 is a 7-year-old female with a novel c.1195 G>A (p.V399M) mutation not previously documented in the literature, however is predicted to be disease causing based on in silico analysis. Patient 2 presented with continuous polymyoclonus and limb myoclonus, another new phenotype in patients with KCNA2 mutations. Patient 3 is a 23-year-old male who has a c.899C>T (p.A297T) mutation, which is a location previously reported however a novel amino acid substitution. Patient 3 presented with superrefractory status epilepticus, yet another novel seizure type for patients with KCNA2 mutations.
Conclusions: We have identified 3 new patients with KCNA2 mutations with novel characteristics as compared to previously reported cases, including electrical status epilepticus of sleep, continuous myoclonus and status epilepticus. These results expand the spectrum of epileptic manifestations of KCNA2 mutations.
Disclosure: Dr. Sachdev has nothing to disclose. Dr. Gaínza-Lein has nothing to disclose. Dr. Tchapyjnikov has nothing to disclose. Dr. Loddenkemper has received personal compensation in an editorial capacity for Seizure, Epilepsy Currents, and Wyllie’s Treatment of Epilepsy 6th edition. Dr. Mikati has nothing to disclose.
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