Genetic diagnosis and clinical characteristics by etiological classification in early-onset epileptic encephalopathy with burst suppression pattern

• Published in: Epilepsy research 2020-07, Vol.163, p.106323-106323, Article 106323
• Main Authors: Lee, Sangbo, Kim, Se Hee, Kim, Borahm, Lee, Seung-Tae, Choi, Jong Rak, Kim, Heung Dong, Lee, Joon Soo, Kang, Hoon-Chul
• Format: Article
• Language: English
• Subjects: Early infantile epileptic encephalopathy; Early myoclonic encephalopathy; Early-onset epileptic encephalopathy with burst-suppression (EOEE-BS); Ohtahara syndrome
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2020.106323

•Precise etiological diagnosis of EOEE-BS may be helpful in identifying clinical features and prognosis.•Molecular etiology may comprise a significant proportion of EOEE-BS, irrespective of structural abnormalities.•Targeted gene sequencing is an effective tool for diagnosing the genetic background of patients with EOEE-BS.•Treatment options can differ depending on the etiological diagnosis, with surgical treatment being a consideration in patients diagnosed with cortical dysplasia regardless of genetic background. Early-onset epileptic encephalopathies with burst suppression (EOEE-BS) are a group of neonatal epileptic syndromes characterized by intractable epilepsy and severe psychomotor delay with structural and metabolic factors accounting for major etiologies. However, recent advances in gene sequencing have identified that genetic factors might also play a significant role in the development of EOEE-BS. Herein, we used various genetic tests to identify pathogenic genetic variants in EOEE-BS irrespective of structural malformations and analyzed the clinical features associated with each different etiology. A total of 48 patients with EOEE-BS were included. Except for patients with severe hypoxic damage, patients with structural malformations were included in our patient cohort. Clinical features of the patients were reviewed, and etiological diagnoses were made based on several genetic tests, metabolic studies, and radiological findings. A genetic diagnosis was made in 31 (64.6 %) patients, with the most commonly diagnosed gene being STXBP1 (n = 13, 27.1 %), followed by KCNQ2 (n = 5, 10.4 %), SCN2A (n = 5, 10.4 %), DEPDC5 (n = 3, 6.3 %), CASK (n = 1, 2.1 %), CDKL5 (n = 1, 2.1 %), GNAO1 (n = 1, 2.1 %), SLC6A8 (n = 1, 2.1 %), and LIS1 deletion (n = 1, 2.1 %). Other than the classification of epilepsy syndrome, no clinical features were associated with the genetically diagnosed group. Among eight patients with structural malformations, genetic diagnosis was achieved in five (62.5 %), and those patients had pathogenic mutations in DEPDC5 and CASK or LIS1 deletion, indicating the significance of gene sequencing irrespective of structural abnormalities. Treatment responses to a variety of medications and the ketogenic diet differed by etiology, and surgical resection proved to be effective in patients with cortical dysplasia. Genetic etiologies are an important factor in EOEE-BS irrespective of structural malformations and the treatment options may differ by