Authors
David Ledingham, Lou Wiblin, Naomi Warren, Rita Horvath, David J Burn, Mark R Baker
Published in
Movement disorders clinical practice. Aug 16, 2026. Epub Aug 16, 2026.
Abstract
DYT-PRKRA (formerly DYT16) is an autosomal recessive dystonia-parkinsonism syndrome caused by biallelic pathogenic variants in PRKRA, a gene encoding the stress-responsive protein PACT. While early-onset generalized dystonia and speech disturbance are well-recognized features, pathological startle has not previously been described.
We report two siblings with genetically confirmed DYT-PRKRA (homozygous pathogenic PRKRA variant p.Pro222Leu). Case 1, a 37-year-old male, presented with childhood-onset dystonia and persistent pathological startle. Case 2, a 33-year-old female, showed milder dystonia but disabling startle episodes with psychosocial impact. Neurophysiology revealed non-habituating pathological startle responses, with short-latency EMG bursts across proximal and distal muscles consistent with brainstem hyperexcitability.
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-SGCE and idiopathic dystonias, brainstem hyperexcitability is recognized, but PRKRA directly modulates PKR within the integrated stress response, suggesting a unique vulnerability in stress-sensitive reflex circuits.
These cases expand the clinical phenotype of DYT-PRKRA to include pathological startle, a feature not previously reported in PRKRA-related disease and highlight the importance of neurophysiological evaluation in phenotyping genetically confirmed dystonias.
PMID:
42604811
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.
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