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. 2024 Mar;65(3):766-778.
doi: 10.1111/epi.17857. Epub 2023 Dec 22.

Common genes and recurrent causative variants in 957 Asian patients with pediatric epilepsy

Se Hee Kim  1   2 , Jieun Seo  3 , Soon Sung Kwon  3 , Lip-Yuen Teng  4 , DongJu Won  3 , Saeam Shin  3 , Joon Soo Lee  1   2 , Seung-Tae Lee  3 , Jong Rak Choi  3 , Hoon-Chul Kang  1   2
Affiliations

Common genes and recurrent causative variants in 957 Asian patients with pediatric epilepsy

Se Hee Kim et al. Epilepsia. 2024 Mar.

Abstract

Objective: We aimed to identify common genes and recurrent causative variants in a large group of Asian patients with different epilepsy syndromes and subgroups.

Methods: Patients with unexplained pediatric-onset epilepsy were identified from the in-house Severance Neurodevelopmental Disorders and Epilepsy Database. All patients underwent either exome sequencing or multigene panels from January 2017 to December 2019, at Severance Children's Hospital in Korea. Clinical data were extracted from the medical records.

Results: Of the 957 patients studied, 947 (99.0%) were Korean and 570 were male (59.6%). The median age at testing was 4.91 years (interquartile range, 1.53-9.39). The overall diagnostic yield was 32.4% (310/957). Clinical exome sequencing yielded a diagnostic rate of 36.9% (134/363), whereas the epilepsy panel yielded a diagnostic rate of 29.9% (170/569). Diagnostic yield differed across epilepsy syndromes. It was high in Dravet syndrome (87.2%, 41/47) and early infantile developmental epileptic encephalopathy (60.7%, 17/28), but low in West syndrome (21.8%, 34/156) and myoclonic-atonic epilepsy (4.8%, 1/21). The most frequently implicated genes were SCN1A (n = 49), STXBP1 (n = 15), SCN2A (n = 14), KCNQ2 (n = 13), CDKL5 (n = 11), CHD2 (n = 9), SLC2A1 (n = 9), PCDH19 (n = 8), MECP2 (n = 6), SCN8A (n = 6), and PRRT2 (n = 5). The recurrent genetic abnormalities included 15q11.2 deletion/duplication (n = 9), Xq28 duplication (n = 5), PRRT2 deletion (n = 4), MECP2 duplication (n = 3), SCN1A, c.2556+3A>T (n = 3), and 2q24.3 deletion (n = 3).

Significance: Here we present the results of a large-scale study conducted in East Asia, where we identified several common genes and recurrent variants that varied depending on specific epilepsy syndromes. The overall genetic landscape of the Asian population aligns with findings from other populations of varying ethnicities.

Keywords: Lennox-Gastaut syndrome; NGS; developmental epileptic encephalopathy; infantile spasms; neurodevelopmental disorder.

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References

REFERENCES

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Supplementary concepts