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Advances in hyperekplexia and other startle syndromes

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Abstract

Startle, a basic alerting reaction common to all mammals, is described as a sudden involuntary movement of the body evoked by all kinds of sudden and unexpected stimulus. Startle syndromes are heterogeneous groups of disorders with abnormal and exaggerated responses to startling events, including hyperekplexia, stimulus-induced disorders, and neuropsychiatric startle syndromes. Hyperekplexia can be attributed to a genetic, idiopathic, or symptomatic cause. Excluding secondary factors, hereditary hyperekplexia, a rare neurogenetic disorder with highly genetic heterogeneity, is characterized by neonatal hypertonia, exaggerated startle response provoked by the sudden external stimuli, and followed by a short period of general stiffness. It mainly arises from defects of inhibitory glycinergic neurotransmission. GLRA1 is the major pathogenic gene of hereditary hyperekplexia, along with many other genes involved in the function of glycinergic inhibitory synapses. While about 40% of patients remain negative genetic findings. Clonazepam, which can specifically upgrade the GABARA1 chloride channels, is the main and most effective administration for hereditary hyperekplexia patients. In this review, with the aim at enhancing the recognition and prompting potential treatment for hyperekplexia, we focused on discussing the advances in hereditary hyperekplexia genetics and the expound progress in pathogenic mechanisms of the glycinergic-synapse-related pathway and then followed by a brief overview of other common startle syndromes.

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Prof. Cao is in charge of National Natural Science Foundation of China (No.81870889 and 82071258).

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  1. Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yi Shan Road, Shanghai, 200233, China

    Fei-xia Zhan, Shi-Ge Wang & Li Cao

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Dr. Zhan and Dr. Wang contributed in manuscript preparation by performing the literature review and writing the first draft. Prof. Cao critically revised the work.

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Zhan, Fx., Wang, SG. & Cao, L. Advances in hyperekplexia and other startle syndromes. Neurol Sci 42, 4095–4107 (2021). https://doi.org/10.1007/s10072-021-05493-8

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  • DOI: https://doi.org/10.1007/s10072-021-05493-8

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