{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:12:33Z","timestamp":1762917153306},"reference-count":30,"publisher":"Royal College of Psychiatrists","issue":"2","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"unspecified","delay-in-days":7641,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[1997,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hyperekplexia is a rare but well-delineated clinical syndrome of pathological startle response and neonatal hypertonia. Many cases result from mutations in the \u03b1<jats:sub>1<\/jats:sub>subunit of the glycine receptor (GLRA 1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The clinical features, management and recent genetic studies of hyperekplexia are reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 \u03b2 subunit of the glycine receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.170.2.106","type":"journal-article","created":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T05:36:56Z","timestamp":1224049016000},"page":"106-108","source":"Crossref","is-referenced-by-count":30,"title":["Hyperekplexia: abnormal startle response due to glycine receptor mutations"],"prefix":"10.1192","volume":"170","author":[{"given":"Martin","family":"Andrew","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"170","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"S000712500014615X_ref8","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.7.1123"},{"key":"S000712500014615X_ref24","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410150107"},{"key":"S000712500014615X_ref12","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1983.04050040076015"},{"key":"S000712500014615X_ref19","doi-asserted-by":"crossref","first-page":"18739","DOI":"10.1016\/S0021-9258(17)32229-9","article-title":"Startle disease mutations reduce the agonist sensitivity of the human glycine receptor","volume":"268","author":"Rajendra","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"S000712500014615X_ref16","first-page":"420","article-title":"A novel mutation (Gln266$ArHis) in the alpha I subunit of the inhibitory glycine-receptor gene (GLRA 1) in hereditary hyperekplexia (letter)","volume":"58","author":"Milani","year":"1996","journal-title":"American Journal of Human Genetics"},{"key":"S000712500014615X_ref30","doi-asserted-by":"publisher","DOI":"10.1038\/298655a0"},{"key":"S000712500014615X_ref20","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.12.2175"},{"key":"S000712500014615X_ref7","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-305"},{"key":"S000712500014615X_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(89)90041-6"},{"key":"S000712500014615X_ref15","first-page":"909","article-title":"Hereditary stiff baby syndrome","volume":"135","author":"Linganm","year":"1981","journal-title":"American Journal of Diseases of Children"},{"key":"S000712500014615X_ref17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1982.tb01393.x"},{"key":"S000712500014615X_ref27","first-page":"A242","article-title":"Mutational and haplotype analysis of the $1 subunit of the glycine receptor in hyperekplexia patients","volume":"55","author":"Shiang","year":"1994","journal-title":"American Journal of Human Genetics"},{"key":"S000712500014615X_ref23","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-131"},{"key":"S000712500014615X_ref13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.19.7394"},{"key":"S000712500014615X_ref4","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/BF02335749","article-title":"Hyperekplexia and stiff-baby syndrome: an identical neurological disorder","volume":"14","author":"Cloni","year":"1993","journal-title":"Italian Journal of Neurological Sciences"},{"key":"S000712500014615X_ref10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.1958.tb03533.x"},{"key":"S000712500014615X_ref11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(62)92475-3"},{"key":"S000712500014615X_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)90398-M"},{"key":"S000712500014615X_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(92)90073-8"},{"key":"S000712500014615X_ref21","first-page":"A61","article-title":"Hereditary startle disease. 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