DYT
‐
PRKRA
Dystonia‐Parkinsonism with Pathological Startle: Expanding the Phenotype of
PRKRA
‐Related Disease
David Ledingham, Lou Wiblin, Naomi Warren, Rita Horvath, David J. Burn, Mark R. Baker Abstract
Background
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.
Cases
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.
Literature review
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.
Conclusions
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.