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KCNT1‐related epilepsy: An international multicenter cohort of 27 pediatric cases
Author(s) -
Borlot Felippe,
Abushama Ahmed,
MorrisonLevy Nadine,
Jain Puneet,
Puthenveettil Vinayan Kollencheri,
Abukhalid Musaad,
Aldhalaan Hesham M.,
Almuzaini Hanin S.,
Gulati Sheffali,
Hershkovitz Tova,
Konanki Ramesh,
Lingappa Lokesh,
Luat Aimee F.,
Shafi Shatha,
Tabarki Brahim,
Thomas Maya,
Yoganathan Sangeetha,
Alfadhel Majid,
Arya Ravindra,
Donner Elizabeth J.,
Ehaideb Salleh N.,
Gowda Vykuntaraju K.,
Jain Vivek,
Madaan Priyanka,
Myers Kenneth A.,
Otsubo Hiroshi,
Panda Prateek,
Sahu Jitendra K.,
Sampaio Letícia P. B.,
Sharma Suvasini,
SimardTremblay Elisabeth,
Zak Maria,
Whitney Robyn
Publication year - 2020
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16480
Subject(s) - cohort , epilepsy , medicine , pediatrics , white matter , corpus callosum , magnetic resonance imaging , pathology , psychiatry , radiology
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.