UNASSIGNED: Early onset @entity302 (EOEEs) represent a significant diagnostic challenge. Newer genomic approaches have begun to elucidate an increasing number of responsible single genes as well as emerging diagnostic strategies. In this single-center study, we aimed to investigate a cohort of @entity1 with unexplained EOEE. We performed whole-exome sequencing (WES), targeting a list of 137 @entity302 -associated genes on 50 @entity1 with unexplained EOEE. We characterized all phenotypes in detail and classified @entity1 according to known electroclinical syndromes where possible. @entity1 with previous genetic diagnoses, causative @entity75 , or @entity2246 were excluded. We identified disease-causing variants in 11 @entity1 (22%) in the following genes: @entity13263 (n = 3), @entity9402 (n = 2), @entity69076 , @entity8031 , @entity8027 , @entity11588 , @entity47588 , and @entity9401 . We also identified two further variants (in @entity2374 and @entity8045 ) in two @entity1 requiring further investigation. Eleven variants were de novo, and in one paternal testing was not possible. Phenotypes were broadened for some variants identified. This study demonstrates that WES is a clinically useful screening tool for previously investigated unexplained EOEE and allows for reanalysis of data as new genes are being discovered. Detailed phenotyping allows for expansion of specific @entity2526 leading to @entity302 and emerging sub-phenotypes.

Unexplained early onset XXXX : Exome screening and phenotype expansion.

@entity1 :: ('9606', 'Species') :: ['children', 'Infants'] @entity11588 :: ('2903', 'Gene') :: ['GRIN2A'] @entity2374 :: ('2892', 'Gene') :: ['GRIA3'] @entity75 :: ('MESH:D001927', 'Disease') :: ['brain malformations'] @entity9402 :: ('3745', 'Gene') :: ['KCNB1'] @entity8031 :: ('6323', 'Gene') :: ['SCN1A'] @entity8027 :: ('6326', 'Gene') :: ['SCN2A'] @entity8045 :: ('57094', 'Gene') :: ['CPA6'] @entity47588 :: ('1759', 'Gene') :: ['DNM1'] @entity2526 :: ('MESH:D025063', 'Disease') :: ['gene disorders'] @entity13263 :: ('6812', 'Gene') :: ['STXBP1'] @entity302 :: ('MESH:D004827', 'Disease') :: ['epilepsy', 'epileptic encephalopathy', 'epileptic encephalopathies'] @entity69076 :: ('57582', 'Gene') :: ['KCNT1'] @entity9401 :: ('3737', 'Gene') :: ['KCNA2'] @entity2246 :: ('MESH:D008661', 'Disease') :: ['inborn errors of metabolism']
@entity302 :: (MESH:D004827,Disease) :: ['epileptic encephalopathy']
