Objective: To elucidate the cause of dystonia and deafness in a 37-year-old woman and to evaluate the response to deep brain stimulation (DBS).

Background: Dystonia-deafness syndrome (DDS) is a clinical term for a group of disorders with typically early childhood onset of deafness and later occurring dystonia. Mutations in several genes are known to lead to the typical clinical picture. One of these genes is ACTB that, despite an earlier description in 2006, has only recently been clearly linked to DDS in a small number of patients. The ACTB gene encodes ß-actin, an ubiquitously occurring cytoskeletal protein.

Method: n.a.

Results: Here we report on a 37-year-old woman presenting with deafness from early childhood on and severe dystonia as a young adult. At the age of 13 years, a cochlear implant on the left was implanted. She also had global development delay. Retrospectively, she showed writing difficulties in the sense of writer’s dystonia at the age of 18 years. At the age of 25 years, she developed severe generalized dystonia following a gastrointestinal infection requiring intensive medical care. Her dystonia was progressive and accompanied by severe dysarthria. Genetic testing revealed the pathogenic heterozygous variant c.547C>T (p.Arg183Trp) in the ACTB gene on chromosome 7.  As this variant is inherited autosomal dominantly and both parents are unaffected, it is likely that it represents a de novo mutation. At the age of 37 years, the patient underwent bilateral implantation of DBS electrodes in the posteroventrolateral globus pallidus internus resulting in improvement of dystonia, especially in a better understanding of her speech as well as a better ability to walk.

Conclusion: The ACTB p.Arg183Trp mutation should be considered in patients with a combination of deafness and dystonia and appears to represent the only known mutation in this gene to cause this more confined phenotype, whereas other mutations in this gene cause the more complex cerebro-fronto-facial syndrome. The mutation in our patient well explains her clinical presentation that is similar to that of eight previously published patients carrying the same mutation. Genetic testing of dystonia-deafness patients should, however, include the entire ACTB gene and other DDS-related genes due to broad phenotypic overlap. In keeping with previous reports, pallidal DBS appears to be a beneficial treatment option.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/de-novo-s-actin-mutation-as-a-cause-of-seemingly-sporadic-dystonia-deafness-syndrome-responsive-to-deep-brain-stimulation/