Hostname: page-component-76fb5796d-9pm4c Total loading time: 0 Render date: 2024-04-27T01:22:15.225Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access Rights & Permissions [Opens in a new window]

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 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andarmann, F., Keene, D. L., Andarmann, E., et al (1960) Startle disease or hyperekplexia. Further delineation of the syndrome. Brain, 103, 985–997.CrossRefGoogle Scholar
Bacloer, C. M., Hoch, W. & Betz, H. (1988) Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO Journal, 7, 3717–3726.Google Scholar
Buckwaltar, M. S., Cook, S. A., Devisson, M. T., et al (1994) A frameshift mutation in the mouse $1 glycine receptor gene (Gina I) results in progressive neurological symptoms and juvenile death. Human Molecular Genetics, 3, 2025–2030.Google Scholar
Cloni, G. Biagloni, E., Bottai, P., et al (1993) Hyperekplexia and stiff-baby syndrome: an identical neurological disorder Italian Journal of Neurological Sciences, 14, 145–152.Google Scholar
Dooley, J. M. & Andarmann, F. (1989) Startle disease or hyperekplexia: Adolescent onset and response to valproate. Paediatric Neurology, 5, 126–127.Google Scholar
Dubowitz, L. M. S., Bouza, H. Hird, M. F., et al (1992) Low cerebrospinal fluid concentration of free gamma-aminobutyric acid in startle disease. Lancet, 340, 80–81.CrossRefGoogle ScholarPubMed
George, A. L., Crackowar, M. A., Abdalla, J. A., et al (1993) Molecular basis of Thooisens disease (autosonrial dominant myotonia congenita). Nature Genetics, 3, 305–310.Google Scholar
Heine, R., George, A. L., Pika, U. et al (1994) Proof of a non functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion. Human Molecular Genetics, 3, 1123–1128.Google Scholar
Kingmore, S. F., Giros, B., Suh, D. et al (1994) Glycine receptor 3-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nature Genetics, 7, 136–142.CrossRefGoogle Scholar
Kerstein, L. & Silfverskiold, B. P. (1958) A family with emotionally precipitated ‘drop seizures’. Acta Psychiatrica Scandinavica, 33, 471–476.Google Scholar
Kok, O. & Bruyn, G. W. (1962) An unidentified hereditary disease (letter). Lancet, i, 1359.Google Scholar
Kurczyncki, T. W. (1983) Hyperekplexia. Archives of Neurology, 40, 246–248.Google Scholar
Langosch, D., Thomas, L. & Betz, H. (1988) Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer Proceedings of the Natonal Academy of Sciences of the USA, 85, 7394–7398.CrossRefGoogle ScholarPubMed
Langosch, D., Thomas, L., Betz, H., Becloer, C.-M. & Betz, K. (1990) The inhibitory glycine receptor: a ligand-gated chloride channel of the central nervous system. European Journal of Biochemistry, 194, 1–8.Google Scholar
Linganm, S., Wilson, J. & Hart, E. W. (1981) Hereditary stiff baby syndrome. American Journal of Diseases of Children, 135, 909–911.Google Scholar
Milani, N., Dalpra, L., Del Prete, A., et al (1996) A novel mutation (Gln266$ArHis) in the alpha I subunit of the inhibitory glycine-receptor gene (GLRA 1) in hereditary hyperekplexia (letter). American Journal of Human Genetics, 58, 420–422.Google Scholar
Moriey, D. J., Weavar, D. D., Garg, B. R. et al (1982) Hyperekplexia: an inherited disorder of the startle response. Clinical Genetics, 21, 388–396.Google Scholar
Nigro, M. A. & Lim, K. C. N. (1992) Hyperekplexia and sudden neonatal death. Paediatric Neurology, 8, 221–225.Google Scholar
Rajendra, S., Lynch, J. W., Pierce, K. D. et al (1994) Startle disease mutations reduce the agonist sensitivity of the human glycine receptor Journal of Biological Chemistry, 268, 18739–18742.Google Scholar
Rees, M. I., Andrew, M., Jawad, S., et al (1994) Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the $1 subunit of the inhibitory glycine receptor. Human Molecular Genetics, 3, 2175–2179.Google Scholar
Ryan, S. G., Bick, D. P., Macloay, R. N., et al (1989) Hereditary startle disease. Clinical features and response to clonazepam in a large pedigree amenable to linkage analysis (abstract). American Journal of Human Genetics, 45, A61.Google Scholar
Ryan, S. G., Bick, D. P., Macloay, R. N., Sherman, S. L., Terry, J. C., et al (1992) Startle disease, or hyperekplexia: response to clonazepam and assignment of the gene (STHE) to chromosome 5q by linkage analysis. Annals of Neurology, 31, 663–668.CrossRefGoogle ScholarPubMed
Ryan, S. G., Bick, D. P., Macloay, R. N., Sherman, S. L., Terry, J. C., Buchwalter, M. S., Lynch, J. W. et al (1994) A missense mutation in the gene encoding the $1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Nature Genetics, 7, 131–135.Google Scholar
Saanz-Lope, E., Herranz-Tanarro, R J., Masdue, J. C., et al (1984) Hyperekplexia: a syndrome of pathological startle responses. Annals of Neurology, 15, 36–41.Google Scholar
Schorderet, D. F., Pescia, G., Bernasconi, A., et al (1994) An additional family with startle disease on a G1192A mutation at the a, subunit of the inhibitory glycine receptor gene. Human Molecular Genetics, 3, 1201.Google Scholar
Shiang, R., Ryan, S. G., Zhu, Y.-Z. et al (1993) Mutations in the $1 subunit of the inhibitory gene receptor cause the dominant neurological disorder, hyperekplexia. Nature Genetics, 5, 351–357.Google Scholar
Shiang, R., Ryan, S. G., Zhu, Y.-Z., et al (1994) Mutational and haplotype analysis of the $1 subunit of the glycine receptor in hyperekplexia patients. American Journal of Human Genetics, suppl. 55, A242.Google Scholar
Steinmeyer, K., Lorenz, C., Pusch, M., et al (1994) Multimeric structure of CIC-I chloride channel revealed by mutations in dominant myotonia congenita. EMBO Journal, 13, 737–743.Google Scholar
Suhren, O., Bruyn, G. W. & Tuynman, J. A. (1966) Hyperekplexia. A hereditary startle syndrome. Journal of Neurological Science, 3, 577–605.Google Scholar
White, W. F. & Heller, A. K. (1982) Glycine receptor alteration in the mutant mouse spastic. Nature, 298, 655–657.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.