{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T01:25:18Z","timestamp":1786929918403,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      DYT\u2010PRKRA (formerly DYT16) is an autosomal recessive dystonia\u2010parkinsonism syndrome caused by biallelic pathogenic variants in\n                      <jats:italic>PRKRA<\/jats:italic>\n                      , a gene encoding the stress\u2010responsive protein PACT. While early\u2010onset generalized dystonia and speech disturbance are well\u2010recognized features, pathological startle has not previously been described.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Cases<\/jats:title>\n                    <jats:p>\n                      We report two siblings with genetically confirmed DYT\u2010PRKRA (homozygous pathogenic\n                      <jats:italic>PRKRA<\/jats:italic>\n                      variant p.Pro222Leu). Case 1, a 37\u2010year\u2010old male, presented with childhood\u2010onset dystonia and persistent pathological startle. Case 2, a 33\u2010year\u2010old female, showed milder dystonia but disabling startle episodes with psychosocial impact. Neurophysiology revealed non\u2010habituating pathological startle responses, with short\u2010latency EMG bursts across proximal and distal muscles consistent with brainstem hyperexcitability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Literature review<\/jats:title>\n                    <jats:p>\n                      Startle responses are classically associated with hyperekplexia but may occur in other movement disorders. Reflex hyperexcitability is seen in dystonia, yet overt startle is rarely reported. In DYT\u2010SGCE and idiopathic dystonias, brainstem hyperexcitability is recognized, but\n                      <jats:italic>PRKRA<\/jats:italic>\n                      directly modulates PKR within the integrated stress response, suggesting a unique vulnerability in stress\u2010sensitive reflex circuits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These cases expand the clinical phenotype of DYT\u2010PRKRA to include pathological startle, a feature not previously reported in\n                      <jats:italic>PRKRA<\/jats:italic>\n                      \u2010related disease and highlight the importance of neurophysiological evaluation in phenotyping genetically confirmed dystonias.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mdc3.70784","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T01:22:40Z","timestamp":1786929760000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>DYT<\/scp>\n                    \u2010\n                    <scp>PRKRA<\/scp>\n                    Dystonia\u2010Parkinsonism with Pathological Startle: Expanding the Phenotype of\n                    <scp>PRKRA<\/scp>\n                    \u2010Related Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-2666","authenticated-orcid":false,"given":"David","family":"Ledingham","sequence":"first","affiliation":[{"name":"Neurosciences Newcastle Upon Tyne NHS Foundation Trust  Newcastle upon Tyne UK"},{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"},{"name":"NIHR Newcastle Biomedical Research Centre (BRC)  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lou","family":"Wiblin","sequence":"additional","affiliation":[{"name":"Neurosciences Department South Tees Hospital NHS Foundation Trust  Middlesbrough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Warren","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-170X","authenticated-orcid":false,"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Burn","sequence":"additional","affiliation":[{"name":"President's Office, University of Galway  Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6916-1329","authenticated-orcid":false,"given":"Mark R.","family":"Baker","sequence":"additional","affiliation":[{"name":"Neurosciences Newcastle Upon Tyne NHS Foundation Trust  Newcastle upon Tyne UK"},{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"},{"name":"NIHR Newcastle Biomedical Research Centre (BRC)  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"issue":"2","key":"e_1_2_10_2_1","article-title":"Siblings with a PRKRA (DYT16) mutation and startle myoclonus","volume":"33","author":"Wiblin L","year":"2018","journal-title":"Mov Disord"},{"issue":"3","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1111\/j.1469-7793.1999.0931u.x","article-title":"Patterned ballistic 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