title: Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2.
abstract: BACKGROUND
  Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development. Several genes have been associated with EOEE and a molecular diagnosis workup is challenging since similar phenotypes are associated with mutations in different genes and since mutations in one given gene can be associated with very different phenotypes. Recently, de novo mutations in KCNQ2, have been found in about 10% of EOEE patients. Our objective was to confirm that KCNQ2 was an important gene to include in the diagnosis workup of EOEEs and to fully describe the clinical and EEG features of mutated patients.
  
  
  METHODS
  We have screened KCNQ2 in a cohort of 71 patients with an EOEE, without any brain structural abnormality. To be included in the cohort, patient's epilepsy should begin before three months of age and be associated with abnormal interictal EEG and neurological impairment. Brain MRI should not show any structural abnormality that could account for the epilepsy.
  
  
  RESULTS
  Out of those 71 patients, 16 had a de novo mutation in KCNQ2 (23%). Interestingly, in the majority of the cases, the initial epileptic features of these patients were comparable to those previously described in the case of benign familial neonatal epilepsy (BFNE) also caused by KCNQ2 mutations. However, in contrast to BFNE, the interictal background EEG was altered and displayed multifocal spikes or a suppression-burst pattern. The ongoing epilepsy and development were highly variable but overall severe: 15/16 had obvious cognitive impairment, half of the patients became seizure-free, 5/16 could walk before the age of 3 and only 2/16 patient acquired the ability to speak.
  
  
  CONCLUSIONS
  This study confirms that KCNQ2 is frequently mutated de novo in neonatal onset epileptic encephalopathy. We show here that despite a relatively stereotyped beginning of the condition, the neurological and epileptic evolution is variable.
authors.affiliation: INSERM, UMR_S 910 Faculté de médecine, Marseille, France. mathieu.milh@ap-hm.fr
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
authors.forename: Nadia
authors.initials: N
authors.lastname: Boutry-Kryza
authors.forename: Julie
authors.initials: J
authors.lastname: Sutera-Sardo
authors.forename: Cyril
authors.initials: C
authors.lastname: Mignot
authors.forename: Stéphane
authors.initials: S
authors.lastname: Auvin
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacoste
authors.forename: Nathalie
authors.initials: N
authors.lastname: Villeneuve
authors.forename: Agathe
authors.initials: A
authors.lastname: Roubertie
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Heron
authors.forename: Maryline
authors.initials: M
authors.lastname: Carneiro
authors.forename: Anna
authors.initials: A
authors.lastname: Kaminska
authors.forename: Cécilia
authors.initials: C
authors.lastname: Altuzarra
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Blanchard
authors.forename: Dorothée
authors.initials: D
authors.lastname: Ville
authors.forename: Marie Anne
authors.initials: MA
authors.lastname: Barthez
authors.forename: Delphine
authors.initials: D
authors.lastname: Heron
authors.forename: Domitille
authors.initials: D
authors.lastname: Gras
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dorison
authors.forename: Dianne
authors.initials: D
authors.lastname: Doummar
authors.forename: Thierry
authors.initials: T
authors.lastname: Billette de Villemeur
authors.forename: Isabelle
authors.initials: I
authors.lastname: An
authors.forename: Aurélia
authors.initials: A
authors.lastname: Jacquette
authors.forename: Perrine
authors.initials: P
authors.lastname: Charles
authors.forename: Julie
authors.initials: J
authors.lastname: Perrier
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.forename: Laurent
authors.initials: L
authors.lastname: Vercueil
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
authors.forename: Gaétan
authors.initials: G
authors.lastname: Lesca
authors.forename: Laurent
authors.initials: L
authors.lastname: Villard
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010641:Phenotype; D011859:Radiography
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human