KCNT1-related epilepsy: An international multicenter cohort of 27 pediatric cases.

Autor: Borlot F; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada., Abushama A; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada., Morrison-Levy N; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.; Children's Hospital of Eastern Ottawa, Ottawa, Ontario, Canada., Jain P; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.; Division of Pediatric Neurology, Department of Pediatrics, Danat Al Emarat Hospital for Women and Children, Abu Dhabi, United Arab Emirates., Puthenveettil Vinayan K; Department of Pediatric Neurology, Amrita Institute of Medical Sciences, Cochin, India., Abukhalid M; Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Aldhalaan HM; Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Almuzaini HS; Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Gulati S; Child Neurology Division, Department of Pediatrics, Center of Excellence & Advanced Research on Childhood Neurodevelopmental Disorders, All India Institute of Medical Sciences, New Delhi, India., Hershkovitz T; Genetic Institute, Rambam Medical Center, Haifa, Israel., Konanki R; Department of Neurology, Rainbow Children's Hospital, Hyderabad, India., Lingappa L; Department of Neurology, Rainbow Children's Hospital, Hyderabad, India., Luat AF; Detroit Medical Center, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan., Shafi S; Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia., Tabarki B; Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia., Thomas M; Pediatric Neurology, Department of Neurological Sciences, Christian Medical College, Vellore, India., Yoganathan S; Pediatric Neurology, Department of Neurological Sciences, Christian Medical College, Vellore, India., Alfadhel M; King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.; Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia., Arya R; Division of Neurology, Comprehensive Epilepsy Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio., Donner EJ; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada., Ehaideb SN; King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia., Gowda VK; Indira Gandhi Institute of Child Health, Bangalore, India., Jain V; Santokba Durlabhji Hospital, Jaipur, India., Madaan P; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Myers KA; Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.; Department of Neurology & Neurosurgery, McGill University Health Centre, Montreal, Quebec, Canada.; Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada., Otsubo H; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada., Panda P; Child Neurology Division, Department of Pediatrics, Center of Excellence & Advanced Research on Childhood Neurodevelopmental Disorders, All India Institute of Medical Sciences, New Delhi, India., Sahu JK; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Sampaio LPB; Department of Neurology, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil., Sharma S; Neurology Division, Department of Pediatrics, Lady Harding Medical College and Kalawati Saran Children's Hospital, New Delhi, India., Simard-Tremblay E; Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.; Department of Neurology & Neurosurgery, McGill University Health Centre, Montreal, Quebec, Canada., Zak M; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada., Whitney R; Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2020 Apr; Vol. 61 (4), pp. 679-692. Date of Electronic Publication: 2020 Mar 13.
DOI: 10.1111/epi.16480
Abstrakt: Objective: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants.
Methods: A cross-sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.
Results: Twenty-seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two-thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray-white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%-50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.
Significance: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence-based practice is still unavailable.
(Wiley Periodicals, Inc. © 2020 International League Against Epilepsy.)
Databáze: MEDLINE
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