A Woman With a Novel Mutation of THAP1 With a Prominent Response to Deep Brain Stimulation of the Globus Pallidus Internus.

A27-year-oldwomanpresentedwithgeneralizeddystonia thatbeganatage 15yearsasdystonicposturingof the righthandwhenwriting. Shewas diagnosedwith cervical dystonia and botulinum toxin injections were tried, providing minimal pain relief and no improvement of thedystonia. The cervical dystonia was partially responsive to sensory tricks (Video, A). Shewasmost bothered by her cervical dystonia, and disability was 6 on Part II of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). On examination, she had increased rate of eye blinking andoccasional spasms involving the lower face,mouth, and jaw, andmild dysarthria. Severe right torticollis and an intermittent head tremor were present. Dystonic posturing of the right upper extremity and increased handgrip were observed while writing. Mild left foot inversion was present while walking. The Fahn-Marsden Scale score was 16, and TWSTRS Part I score was 20. A trial of carbidopa/ levodopa did not provide benefit. Deep brain stimulation (DBS) surgery targeting the globus pallidus internus(GPi)wasperformed,resultinginmoderate improvement 1monthaftertheprocedure,priortoinitialprogramming(TWSTRSPart I = 18,Fahn-Marsden = 8.5) (Video,B).Sheexperiencedfurtherbenefit2monthsafter initialprogramming(TWSTRSPartI = 13,Fahn-Marsden = 3).Whole-exome sequencing revealed a frameshiftmutation, confirmed as a novel 2–base pair deletion mutation in exon 3 of the THAP1 gene (heterozygous exon 3 c.377_378delCT, p.Pro126Args*2) via full sequencing analysis ofDYT6.