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Hyperekplexia: abnormal startle response due to glycine receptor mutations

Published online by Cambridge University Press:  03 January 2018

Martin Andrew  and
Michael J. Owen
Martin Andrew*
Affiliation:
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff
Michael J. Owen
Affiliation:
Departments of Psychological Medicine and Medical Genetics, University of Wales College of Medicine, Cardiff
*
Michael J. Owen, Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN
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Abstract

Background

Hyperekplexia is a rare but well-delineated clinical syndrome of pathological startle response and neonatal hypertonia. Many cases result from mutations in the α1 subunit of the glycine receptor (GLRA 1).

Method

The clinical features, management and recent genetic studies of hyperekplexia are reviewed.

Results

Diagnosis of the disorder should not be difficult, if one is aware of the syndrome. The treatment of first choice is with the benzodiazepine drug clonazepam, which often causes a dramatic although incomplete diminution of startle. Both recessive and dominant mutations in GLRA 1 have been found in affected individuals. The study of mouse mutants with startle phenotypes suggests that the remainder of cases may well be due to mutations in the β subunit of the glycine receptor.

Conclusions

Hyperekplexia is the first human disease shown to result from mutations within a neurotransmitter gene. The demonstration of both dominant and recessive inheritance resulting from different mutations in the same gene is of considerable interest, as other neuropsychiatric disorders may result from mutations in ligand-gated ion channels. Mutation analysis of GLRA 1 is also likely to be useful as an aid to genetic counselling and in diagnostic evaluation of neonatal hypertonia.

Type
Review Article
Information
The British Journal of Psychiatry , Volume 170 , Issue 2 , February 1997 , pp. 106 - 108
Copyright
Copyright © 1997 The Royal College of Psychiatrists 

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