Sangbo Lee, Se Hee Kim, Heung Dong Kim, Joon Soo Lee, Ara Ko, Hoon-Chul Kang
{"title":"Genetic Diagnosis in Neonatal Encephalopathy With Hypoxic Brain Damage Using Targeted Gene Panel Sequencing.","authors":"Sangbo Lee, Se Hee Kim, Heung Dong Kim, Joon Soo Lee, Ara Ko, Hoon-Chul Kang","doi":"10.3988/jcn.2023.0500","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and purpose: </strong>Neonatal encephalopathy (NE) is a neurological syndrome that presents with severe neurological impairments and complications. Hypoxic-ischemic encephalopathy is a major contributor to poor outcomes, being responsible for 50%-80% of admissions to neonatal intensive care units. However, some cases of NE accompanied by hypoxic brain damage cannot be solely attributed to hypoxia-ischemia. We aimed to identify diverse pathogenic genetic variations that may be associated with cases of NE accompanied by hypoxic brain damage rather than hypoxia-ischemia.</p><p><strong>Methods: </strong>We collected data from 34 patients diagnosed with NE accompanied by hypoxic brain damage over a 10-year period. Patients with the following specific conditions were excluded: 1) premature birth (<32 weeks), 2) no history of hypoxic events, 3) related anomalies, 4) neonatal infections, 5) antenatal or perinatal obstetrical complications, 6) severe hypoxia due to other medical conditions, and 7) early death (within 1 week). A comprehensive review of clinical and radiological features was conducted.</p><p><strong>Results: </strong>A genetic diagnosis was made in 11 (32.4%) patients, with pathogenic variants being identified in the following 9 genes: <i>CACNA1A</i> (<i>n</i>=2), <i>KCNQ2</i> (<i>n</i>=2), <i>SCN2A</i> (<i>n</i>=1), <i>SCN8A</i> (<i>n</i>=1), <i>STXBP1</i> (<i>n</i>=1), <i>NSD1</i> (<i>n</i>=1), <i>PURA</i> (<i>n</i>=1), <i>ZBTB20</i> (<i>n</i>=1), and <i>ENG</i> (<i>n</i>=1). No specific treatment outcomes or clinical features other than preterm birth were associated with the results of the genetic analyses. Personalized treatments based on the results of genetic tests were attempted, such as the administration of sodium-channel blockers in patients with <i>KCNQ2</i> or <i>SCN8A</i> variants and the implementation of a ketogenic diet in patients with <i>STXBP1</i> or <i>SCN2A</i> mutations, which demonstrated some degree of effectiveness in these patients.</p><p><strong>Conclusions: </strong>Genetic analyses may help in diagnosing the underlying etiology of NE and concurrent hypoxic brain damage, irrespective of the initial clinical features.</p>","PeriodicalId":15432,"journal":{"name":"Journal of Clinical Neurology","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372210/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3988/jcn.2023.0500","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background and purpose: Neonatal encephalopathy (NE) is a neurological syndrome that presents with severe neurological impairments and complications. Hypoxic-ischemic encephalopathy is a major contributor to poor outcomes, being responsible for 50%-80% of admissions to neonatal intensive care units. However, some cases of NE accompanied by hypoxic brain damage cannot be solely attributed to hypoxia-ischemia. We aimed to identify diverse pathogenic genetic variations that may be associated with cases of NE accompanied by hypoxic brain damage rather than hypoxia-ischemia.
Methods: We collected data from 34 patients diagnosed with NE accompanied by hypoxic brain damage over a 10-year period. Patients with the following specific conditions were excluded: 1) premature birth (<32 weeks), 2) no history of hypoxic events, 3) related anomalies, 4) neonatal infections, 5) antenatal or perinatal obstetrical complications, 6) severe hypoxia due to other medical conditions, and 7) early death (within 1 week). A comprehensive review of clinical and radiological features was conducted.
Results: A genetic diagnosis was made in 11 (32.4%) patients, with pathogenic variants being identified in the following 9 genes: CACNA1A (n=2), KCNQ2 (n=2), SCN2A (n=1), SCN8A (n=1), STXBP1 (n=1), NSD1 (n=1), PURA (n=1), ZBTB20 (n=1), and ENG (n=1). No specific treatment outcomes or clinical features other than preterm birth were associated with the results of the genetic analyses. Personalized treatments based on the results of genetic tests were attempted, such as the administration of sodium-channel blockers in patients with KCNQ2 or SCN8A variants and the implementation of a ketogenic diet in patients with STXBP1 or SCN2A mutations, which demonstrated some degree of effectiveness in these patients.
Conclusions: Genetic analyses may help in diagnosing the underlying etiology of NE and concurrent hypoxic brain damage, irrespective of the initial clinical features.
背景和目的：新生儿脑病（NE）是一种神经系统综合征，表现为严重的神经系统损伤和并发症。缺氧缺血性脑病是导致不良预后的主要因素，占新生儿重症监护病房收治病例的 50%-80%。然而，一些伴有缺氧性脑损伤的 NE 病例不能完全归咎于缺氧缺血。我们旨在找出可能与伴有缺氧性脑损伤而非缺氧缺血的 NE 病例相关的各种致病基因变异：我们收集了 34 名被诊断为伴有缺氧性脑损伤的 NE 患者 10 年间的数据。排除了以下特殊情况的患者：1）早产儿（结果：11 例早产儿被确诊为遗传性 NE：11名患者（32.4%）被确诊为遗传病，并在以下9个基因中发现了致病变体：CACNA1A（n=2）、KCNQ2（n=2）、SCN2A（n=1）、SCN8A（n=1）、STXBP1（n=1）、NSD1（n=1）、PURA（n=1）、ZBTB20（n=1）和 ENG（n=1）。除早产外，其他特定治疗结果或临床特征均与基因分析结果无关。根据基因检测结果尝试了个性化治疗，如对KCNQ2或SCN8A变异的患者使用钠通道阻滞剂，对STXBP1或SCN2A变异的患者实施生酮饮食，这在一定程度上对这些患者有效：无论最初的临床特征如何，基因分析都有助于诊断 NE 和并发缺氧性脑损伤的潜在病因。
期刊介绍：
The JCN aims to publish the cutting-edge research from around the world. The JCN covers clinical and translational research for physicians and researchers in the field of neurology. Encompassing the entire neurological diseases, our main focus is on the common disorders including stroke, epilepsy, Parkinson''s disease, dementia, multiple sclerosis, headache, and peripheral neuropathy. Any authors affiliated with an accredited biomedical institution may submit manuscripts of original articles, review articles, and letters to the editor. The JCN will allow clinical neurologists to enrich their knowledge of patient management, education, and clinical or experimental research, and hence their professionalism.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
