Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2. - Archive ouverte HAL Access content directly
Journal Articles Orphanet Journal of Rare Diseases Year : 2013

Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2.

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Nadia Boutry-Kryza
  • Function : Author
  • PersonId : 942109
Stéphane Auvin
  • Function : Author
  • PersonId : 938114
Anna Kaminska
  • Function : Author
  • PersonId : 942116
Cécilia Altuzarra
  • Function : Author
  • PersonId : 942117
Gaëlle Blanchard
  • Function : Author
  • PersonId : 942118
Marie Anne Barthez
  • Function : Author
  • PersonId : 942120
Domitille Gras
  • Function : Author
  • PersonId : 942121
Isabelle An
  • Function : Author
  • PersonId : 942123
Julie Perrier
  • Function : Author
  • PersonId : 942126
Bertrand Isidor
  • Function : Author
  • PersonId : 886372
Laurent Vercueil
  • Function : Author
  • PersonId : 942127

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 mutated 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. CONCLUSION: This study confirms that KCNQ2 is frequently mutated in neonatal onset epileptic encephalopathy. We show here that despite a relatively stereotyped beginning of the condition, the evolution is highly variable in terms of epilepsy and of cognitive evolution.
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Dates and versions

inserm-00829466 , version 1 (03-06-2013)

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Cite

Mathieu Milh, Nadia Boutry-Kryza, Julie Sutera-Sardo, Cyril Mignot, Stéphane Auvin, et al.. Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2.. Orphanet Journal of Rare Diseases, 2013, 8 (1), pp.80. ⟨10.1186/1750-1172-8-80⟩. ⟨inserm-00829466⟩
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