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Neurogenetics
Original research
Adult phenotype of KCNQ2 encephalopathy
  1. Stephanie Boets1,
  2. Katrine M Johannesen2,3,
  3. Anne Destree4,
  4. Filippo Manti5,
  5. Georgia Ramantani6,
  6. Gaetan Lesca7,8,
  7. Laurent Vercueil9,
  8. Mary Kay Koenig10,
  9. Pasquale Striano11,12,
  10. Rikke Steensbjerre Møller2,3,
  11. Edward Cooper13,
  12. Sarah Weckhuysen1,14,15
  1. 1 Neurology Department, University Hospital Antwerp, Antwerp, Belgium
  2. 2 Department of Epilepsy Genetics and Personalized Treatment, The Danish Epilepsy Centre Filadelfia, Dianalund, Denmark
  3. 3 Institute for Regional Health Research, University of Southern Denmark, Odense, Denmark
  4. 4 Department of Human Genetics, Institute of Pathology and Genetics, Gosselies, Belgium
  5. 5 Department of Human Neuroscience, University of Rome La Sapienza, Roma, Lazio, Italy
  6. 6 Department of Neuropediatrics, University Children's Hospital, Zurich, Switzerland
  7. 7 Department of Genetics, University Hospitals of Lyon, Lyon, France
  8. 8 Neuroscience Research Center, Claude Bernard Lyon I University, Lyon, France
  9. 9 Grenoble Institute of Neurosciences (GIN), University Grenoble Alpes, La Tronche, France
  10. 10 Department of Pediatrics, University of Texas McGovern Medical School, Houston, Texas, USA
  11. 11 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G Gaslini" Institute, Genova, Italy
  12. 12 Pediatric Neurology and Muscular Diseases Unit, IRCCS’ G Gaslini" Institute, Genova, Italy
  13. 13 Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
  14. 14 Applied & Translational Neurogenomics Group, VIB-Center for Molecular Neurology, VIB, Antwerp, Belgium
  15. 15 Translational Neuroscience Group, University of Antwerp, Antwerp, Belgium
  1. Correspondence to Prof. Dr. Sarah Weckhuysen; sarah.weckhuysen{at}uantwerpen.vib.be

Abstract

Background Pathogenic KCNQ2 variants are a frequent cause of developmental and epileptic encephalopathy.

Methods We recruited 13 adults (between 18 years and 45 years of age) with KCNQ2 encephalopathy and reviewed their clinical, EEG, neuroimaging and treatment history.

Results While most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood. The most common seizure type was tonic seizures (early) infancy, and tonic-clonic and focal impaired awareness seizures later in life. Ten individuals (77%) were seizure-free at last follow-up. In 38% of the individuals, earlier periods of seizure freedom lasting a minimum of 2 years followed by seizure recurrence had occurred. Of the 10 seizure-free patients, 4 were receiving a single antiseizure medication (ASM, carbamazepine, lamotrigine or levetiracetam), and 2 had stopped taking ASM. Intellectual disability (ID) ranged from mild to profound, with the majority (54%) of individuals in the severe category. At last contact, six individuals (46%) remained unable to walk independently, six (46%) had limb spasticity and four (31%) tetraparesis/tetraplegia. Six (46%) remained non-verbal, 10 (77%) had autistic features/autism, 4 (31%) exhibited aggressive behaviour and 4 (31%) destructive behaviour with self-injury. Four patients had visual problems, thought to be related to prematurity in one. Sleep problems were seen in six (46%) individuals.

Conclusion Seizure frequency declines over the years and most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are common during childhood and adolescence. Most adult patients have severe ID. Motor, language and behavioural problems are an issue of continuous concern.

  • epilepsy
  • prognosis
  • genetics
  • medical
  • phenotype
  • congenital
  • hereditary
  • and neonatal diseases and abnormalities

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/jmedgenet-2020-107449

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Contributors SW, SB: design of the study, acquisition and interpretation of data, drafting of the manuscript, revision of the manuscript for intellectual content. EC: acquisition and interpretation of data, drafting of the manuscript, revision of the manuscript for intellectual content. KMJ, AD, FM, GR, GL, LV, MKK, PS, RSM: acquisition of data, revision of the manuscript for intellectual content.

    • Funding EC received support for this work from the Jack Pribaz Foundation and the Miles Family fund. PS developed this work within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (Law 232 of 2016). SW received support from FWO-FKM (1861419N), Jack Pribaz Foundation, KCNQ2 Cure and KCNQ2 e.v. The funders supported the (co)authors for their time dedicated to this study, but were not involved in study design, collection, analysis and interpretation of data, writing of the manuscript, or the decision to submit the manuscript for publication.

    • Competing interests EC is a consultant to Xenon Pharmaceuticals and Knopp Biosciences; his participation in this work has been reviewed and approved by Baylor College of Medicine in accordance with institutional conflict of interest policies. MKK serves on speakers bureaus for Greenwich, Novartis and Lundbeck, and on an advisory board for Stealth Biotherapeutics. PS received fees from Ultragenyx, Zogenyx, Biomarin, PTC pharmaceuticals, GW pharma, Neuraxpharma and research grants from GW pharma, PTC Pharmaceuticals, ENECTA SV, Kolfarma, and has been investigator for clinical trials for Ultragenyx and Zogenix. SW received speaker and consultancy fees from UCB, Xenon, Zogenix, Lundbeck and Biocodex.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.