Clinical and genetic analysis of neonatal hyperekplexia caused by GLRB mutations and its literature review

Abstract:

Objective：To report the clinical and genetic features of a newborn with hyperekplexia，to review the related literature and to investigate the early diagnosis and treatment of neonatal hyperekplexia. Methods：The clinical and genetic data of a newborn diag－nosed with hyperekplexia，who was admitted to our NICU in September，2019，was analyzed. In addition，key words including “Neonatal hyperekplexia”，“newborn” and “startle disease” were searched in Wan Fang and PubMed database（from establishment to September，2019），and cases with early diagnosis at home and abroad（within 2 months）were summarized and analyzed by positive gene test. Results：A total of 19 cases（one case in our hospital and 18 cases from reports） were analyzed. Onset of all patients was in the neonatal period，and patients had excessive startle response to unpredictable stimulation，among which 57.8% patients（including one patient in our hospital） had tonic-apneic spells requiring resuscitation. All cases were positive in nose-tapping test，and there was no specific abnormality in EEG and cephalography. Clonazepam has a good effect on this disease. Vigerano manoenvre was able to alle－viate the acute attack. In our report，gene variation detected by all exon gene sequencing was consistent with clinical condition. The gene mutation GLRB c.844_846delGTT p.（Val282del） originated from father and GLRB c.527G>A p.（Argl76Lys） from mother. A total of 73.6% included patients were GLRA1 mutations，15.8% SLC6A5 mutations and 10.5% GLRB mutations. Conclusion：Patient in this study has the typical clinical manifestation of hyperek－plexia and gene mutation analysis demonstrates that it is corre－lated with GLRB mutation. The disease can be treated but usu－ally be misdiagnosed，often occurs life-threatening systemic stiffness and apnoea attack in the neonatal period，suggesting the importance of early diagnosis. The positive result of nose-tapping test can be used as the characteristic clue of diagnosis. Because multiple genes are involved，the whole exon second generation gene can be sequenced. Clonazepam has a good effect on this disease，but the accurate dosage and time need further clinical study.