Objective: This is the phenotypic description of two families affected by hereditary dystonia associated to gene ANO3 mutation (DYT24), one with a heterozygous verisimilarly pathogenic variant (hVPV), and the other with a heterozygous variant of uncertain meaning (hVUM).

Background: ANO3 gene encodes for a Ca2þ-gated chloride channel. DYT24 has an adult onset and usually presents with cranio-cervical dystonia combined with tremor.

Method: Phenomenology description (with related videos), next generation sequencing of dystonia genetic panel, multichannel EMG were performed in both families.

Results: In one family, proband was the mother, who presented a severe axial dystonia associated with tremor at the head and upper limbs, whereas her son had a cranio-cervical dystonia and head jerky movements. Genetic analysis identified a hVPV in ANO3 gene. At NGS a PINK1 gene hVUM was found in the proband and the son displayed in addition of the ANO3 mutation a heterozygous mutation in PANK2 gene. Both patients are under deep brain stimulation of internal globus pallidus from 12 years with benefits that were more evident during the first five years after the operation. In the other family, proband is a 60 y.o. man who presented cranial dystonia (Meige-type) and upper limbs dystonic tremor, whereas his sister shows just dystonic features of Meige syndrome. The ANO3 mutation identified in the proband was a hVUM and, genetic analysis is still ongoing for the sister. Molecular confirm of the same mutation of ANO3 in the sister would suggest the identification of a new mutation. In both families the electrophysiological assessment was consistent with a jerky tremor of the head (family 1), and of the arm (family 2), recordings were not suggestive of myoclonus. All patients are under treatment with botulinum toxin with benefits. They all reported dystonia onset before the age of 20 year. Brain MRI scan showed normal findings in all of them.

Conclusion: DYT24 has heterogeneous clinical aspects, both families here reported have cranio-cervical and upper limb impairment but with different clinical presentation. Patients of the same family are similar but show significant differences with subjects of the other family.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotypic-description-of-two-unreported-families-with-ano3-dystonia/