Objective: To describe the clinical presentation of a case of TUBB4A dystonia with a novel genetic variant

Background: A missense variant at Arg2Gly in the tubulin beta 4-A (TUBB4A) gene is most commonly implicated in whispering dystonia, DYT4. We present a patient with generalized dystonia, including spasmodic dysphonia, found to have a novel TUBB4A variant in Arg121Trp.

Method: The patient is a 64 year old right-handed woman with generalized dystonia. She is of Scandinavian and Czechoslovakian descent. She has four brothers, one of whom has cervical dystonia status post rhizotomy and has arm tremor beginning at age 22 years old. No other family members are symptomatic. She noted speech difficulties around age 2 then developed trouble lifting her legs and walking at age 9. Described as “never athletic,” she remained ambulatory until menopause when gait progressively worsened. She began using a voice amplifier at age 52 years old. Mobility is achieved through crawling.

Neurologic examination revealed a woman with severe scoliosis. Speech with marked spasmodic dysphonia required a voice amplifier. She had blepharospasm and contractions of the platysma. There was right shoulder elevation with left head shift and ten degree right laterocollis. With touching her chin, she was able to achieve a more neutral head position. She had near constant writhing movements of the neck, arms, and extremities consistent with a mobile dystonia. To write, she positioned herself with one knee flexed on a chair and the other leg placed on the ground; she gripped the pen tightly in her left hand and used the right hand to brace herself. She mobilized independently by crawling with her right leg flexed into her chest and the left leg flexed with the knee on the ground. With use of a walker, she leaned on the walker and stepped forward with her left leg then moved her right leg towards her left in a hopping motion, consistent with a hobbyhorse gait.

Results: Genetic testing revealed a variant at codon 121 of the TUBB4A protein in exon 4, replacing arginine with tryptophan (Arg121Trp). MRI Brain was ordered and is pending, as patient requires sedation. Discussion regarding DBS and genetics of family members is ongoing.

Conclusion: We describe a case of TUBB4A dystonia with a novel variant presenting with a mobile generalized dystonia and spasmodic dysphonia with childhood onset. To date no patients with TUBB4A have had DBS, for which she is undergoing evaluation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-variant-of-tubb4a-dystonia-dyt4-a-case-report/