Tamimi Motaz, Oweidat Majd, Atawneh Hamza, Alra'e Mohammed, Amr Bahaa, Gharaibiah Mohammad, Aldwaik Mohammed, Alqam Mariam
College of Medicine, Hebron University, Hebron, West Bank, Palestine.
Division of Child Neurology, Department of Pediatrics, Al-Ahli Hospital, Hebron, West Bank, Palestine.
Ann Med Surg (Lond). 2025 Apr 4;87(5):2562-2567. doi: 10.1097/MS9.0000000000003258. eCollection 2025 May.
Hereditary hyperekplexia (HKPX) is a rare neurogenetic disorder caused by mutations in glycine signaling genes, such as GLRB. We report two neonates with autosomal recessive HKPX2 due to a novel GLRB mutation (c.1414C>T, p.Arg472*).
Case 1, a 1-month-old female, presented with severe startle responses and tonic episodes, normal EEG, and no developmental delays. Case 2, a 2-week-old male, showed similar symptoms but with generalized rhythmic ictal fast activity on EEG. Both had consanguineous parents and unremarkable brain MRIs. Whole exome sequencing identified the same homozygous GLRB mutation in both cases. Treatment with Clonazepam and Levetiracetam significantly improved symptoms.
This is the first report of the c.1414C>T (p.Arg472*) mutation in GLRB, expanding the genetic spectrum of HKPX2. The differing EEG findings highlight the disorder's phenotypic variability. Early diagnosis and treatment are crucial to prevent complications like hypoxia and SIDS.
This article reports a novel GLRB mutation in two neonates with autosomal recessive HKPX2, presenting with divergent EEG findings.
遗传性易惊症（HKPX）是一种由甘氨酸信号基因（如GLRB）突变引起的罕见神经遗传疾病。我们报告了两名因新型GLRB突变（c.1414C>T，p.Arg472*）导致常染色体隐性HKPX2的新生儿。
病例1是一名1个月大的女性，表现出严重的惊吓反应和强直性发作，脑电图正常，且无发育迟缓。病例2是一名2周大的男性，表现出类似症状，但脑电图显示有全身性节律性发作期快速活动。两人的父母均为近亲结婚，脑部MRI检查无异常。全外显子组测序在两个病例中均鉴定出相同的纯合GLRB突变。使用氯硝西泮和左乙拉西坦治疗后症状明显改善。
这是首次报道GLRB基因中的c.1414C>T（p.Arg472*）突变，扩展了HKPX2的遗传谱。脑电图结果的差异突出了该疾病的表型变异性。早期诊断和治疗对于预防缺氧和婴儿猝死综合征等并发症至关重要。
本文报告了两名患有常染色体隐性HKPX2的新生儿中存在新型GLRB突变，并伴有不同的脑电图结果。
