A 6-year-old boy from Maharashtra, India, presented with subacute-onset generalized dystonia after a febrile illness; his sister manifested insidious-onset multifocal dystonia (Video 1). T2-weighted MRI showed striatal hyperintensities (Figure 1). Clinical exome sequencing detected a novel homozygous variant (c.127 G > T; G43C) in the PRKRA gene which encodes PACT, a stress-response protein. The variant was confirmed by Sanger sequencing (eFigure 1, links.lww.com/WNL/C111). DYT-PRKRA is a childhood-onset progressive dystonia.1 Some patients have exacerbation with fever and evidence of striatal degeneration in neuroimaging.2 PACT-dependent activation of protein kinase R (PKR) leads to apoptosis.2 Perhaps, the G43C PACT triggered abnormal activation of PKR and intensified neuronal apoptosis during febrile illness.
Video 1
First segment shows the 6-year-old boy with generalized dystonia and prominent bulbar involvement (jaw-opening dystonia, anarthria); second segment shows his 4-year-old sister with extensor posturing of arms and flexion of hands (especially right) and intermittent right plantar flexion while running.Download Supplementary Video 1 via http://dx.doi.org/10.1212/200858_Video_1
Timeline showing clinical features of the boy (A) and his sister (C); MRI of the boy (B) and his sister (D) showing striatal T2W and FLAIR hyperintensities (arrows) and mild cerebral atrophy (B).
Study Funding
No targeted funding reported.
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Appendix Authors
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was José Merino, MD, MPhil, FAAN.
- Received January 17, 2022.
- Accepted in final form May 2, 2022.
- © 2022 American Academy of Neurology
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