Mutations in KCNQ2 gene, encoding for voltage-gated K+ channel subunit,may result in a wide spectrum of early-onset epileptic disorders. Thephenotype of the disease varies from “benign familial neonatal seizures”to “severe epileptic encephalopathies”. In this report, we present a novelmutation [namely: c.683A>G (p.His228Arg)], as a presumable cause of severeinfantile-onset neonatal seizures, in a 3-month old boy. The seizures havebeen poorly responsive to various pharmacological treatments, with phenytoinand carbamazepine presenting with the most favourable results so far. Thestudy of our patient could help to further clarify the clinical manifestationsof KCNQ2 mutations, revealing a previously unreported mutation.
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1. Miceli F, Vargas E, Bezanilla F, Taglialatela M. Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations in the voltage-sensing domain. Biophys J 2012; 102: 1372-1382.
2. Borgatti R, Zucca C, Cavallini A, et al. A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology 2004; 63: 57-65.
3. Wang HS, Pan Z, Shi W, et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 1998; 282: 1890-1893.
4. Miceli F, Soldovieri MV, Ambrosino P, et al. Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits. J Neurosci 2015; 35: 3782-3793.
5. Singh NA, Westenskow P, Charlier C, et al; BFNC Physician Consortium. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain 2003; 126(Pt 12): 2726-2737.
6. Miraglia del Giudice E, Coppola G, Scuccimarra G, Cirillo G, Bellini G, Pascotto A. Benign familial neonatal convulsions (BFNC) resulting from mutation of the K CNQ2 voltage sensor. Eur J Hum Genet 2000; 8: 994-997.
7. Numis AL, Angriman M, Sullivan JE, et al. KCNQ2 encephalopathy: delineation of the electroclinical phenotype and treatment response. Neurology 2014; 82: 368-370.
8. Milh M, Boutry-Kryza N, Sutera-Sardo J, et al. Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2. Orphanet J Rare Dis 2013, 8: 80.
9. Gürsoy S, Erçal D. Diagnostic approach to genetic causes of early-onset epileptic encephalopathy. J Child Neurol 2016; 31: 523-532.
10. Milh M, Cacciagli P, Ravix C, et al. Severe neonatal seizures: From molecular diagnosis to precision therapy? Rev Neurol (Paris) 2016; 172: 171-173.
11. Battefeld A, Tran BT, Gavrilis J, Cooper EC, Kole MH. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons. J Neurosci 2014; 34: 3719-3732.