Objective: To report on two patients with dystonia-deafness syndrome associated with a mutation in the beta actin gene and a positive effect of pallidal deep brain stimulation.

Background: Dystonia in combination with sensory-neural deafness, also referred to as dystonia deafness syndrome (DDS), can be due to various genetic and acquired causes. ACTB gene mutations are generally associated with the Baraitser-Winter syndrome type 1, characterized by developmental malformations as hypertelorism, cleft palat and high arched eyebrows. DDS in addition to these malformations has only been reported once in two identical twin brothers, with the same mutation as in our patients.

Methods: Report of two patients.

Results: Patient 1, a 22 year-old woman, presented with congenital sensory-neural deafness and generalized dystonia. In addition, she had high arched eyebrows. She suffered from writer’s cramp from the age of 19. After two years, dystonia rapidly progressed to arms, legs, neck, trunk and legs within nine months (BFMDRS 102). Symptoms deteriorated despite L-dopa and trihexiphenidyl medication and botulinum toxin injections. We performed bilateral internal global pallidal deep brain stimulation (GPi-DBS). Combined with botulinum toxin injections in the neck she regained total independence (BFMDRS 48). Patient 2, the index patients mother, was a 49 year-old with sensory-neural hearing loss leading to deafness. At age 16, a slowly progressive dystonia started with a dystonic hand tremor and progression over years to her arms, trunk, neck and legs led to wheelchair dependency at the age of 42 (BFMDRS 78). She is currently awaiting DBS surgery. The positive family history was suggestive of a genetic cause. Mutations in the DYT1 gene, DFN1 gene (Mohr-Tranebjaerg syndrome) and mitochrondrial DNA were excluded. Whole exome sequencing (WES) revealed an ACTB gene mutation (p.Arg183Trp) in mother and daughter.

Conclusions: The p.Arg183Trp mutation in the ACTB gene appears to be associated with the clinical presentation of DDS, also without developmental abnormalities of the Baraitser-Winter syndrome. GPi-DBS in our patient ameliorated her invalidating dystonia and significantly increased her quality of life.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dystonia-deafness-syndrome-caused-by-beta-actin-gene-mutation-and-the-effect-of-pallidal-deep-brain-stimulation/