Abstract
INTRODUCTION: 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*). CASES DESCRIPTION: 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. DISCUSSION: 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. CONCLUSION: This article reports a novel GLRB mutation in two neonates with autosomal recessive HKPX2, presenting with divergent EEG findings.