Year: 2013
Type: article
Study design: Observational Study
Abstract: OBJECTIVES: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy. METHODS: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG. RESULTS: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. CONCLUSION: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible.
Source: Neurology
Authors: Sarah Weckhuysen, Vanja Ivanovic, Rik Hendrickx, Rudy Van Coster, Helle Hjalgrim, Rikke S. Møller, Sabine Grønborg, An-Sofie Schoonjans, Berten Ceulemans, Sinead B. Heavin, Christin Eltze, Rita Horvath, Gianluca Casara, Tiziana Pisano, Lucio Giordano, Kevin Rostasy, Edda Haberlandt, Beate Albrecht, Andrea Bevot, Ira Benkel, Steffan Syrbe, Beth Sheidley, Renzo Guerrini, Annapurna Poduri, Johannes R. Lemke, Simone Mandelstam, Ingrid Scheffer, Marco Angriman, Pasquale Striano, Carla Marini, Arvid Suls, Peter De Jonghe, On behalf of the KCNQ2 Study Group
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: GlaxoSmithKline, Wellcome Trust, European Science Foundation, University of Melbourne, Fonds Wetenschappelijk Onderzoek, Universiteit Antwerpen, Vlaamse regering, Epilepsy Society, Medical Research Council, National Health and Medical Research Council, Health Research Council of New Zealand, Cilag
OpenAlex ID: W2132352566