DYT-PRKRA Dystonia-Parkinsonism with Pathological Startle: Expanding the Phenotype of PRKRA-Related Disease.

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.