Early-Onset Dystonia, Exacerbation With Fever, and Striatal Signal Changes: Emerging Phenotype of DYT-PRKRA.

Abstract

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][1]). 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. [1]: http://links.lww.com/WNL/C111