2015 Articles

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

Park, Jung E.; Vanegas-Arroyave, Nora; Hallett, Mark

A 27-year-old woman presented with generalized dystonia that began at age 15 years as dystonic posturing of the right hand when writing. She was diagnosed with cervical dystonia and botulinum toxin injections were tried, providing minimal pain relief and no improvement of the dystonia. The cervical dystonia was partially responsive to sensory tricks. She was most 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 and occasional spasms involving the lower face, mouth, and jaw, and mild 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) was performed, resulting in moderate improvement 1 month after the procedure, prior to initial programming (TWSTRS Part I = 18, Fahn-Marsden = 8.5). She experienced further benefit 2 months after initial programming (TWSTRS Part I = 13, Fahn-Marsden = 3). Whole-exome sequencing revealed a frameshift mutation, 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 of DYT6.