Objective: To describe the phenotypic and genotypic presentation of a kindred with a novel ANO3 mutation.

Background: Mutations in ANO3 gene cause an autosomal dominant craniocervical dystonia (DYT24), presenting from childhood to middle life. However, in the past few years, the clinical spectrum of this disorder has widened. We present a family with heterogeneous presentation, exemplifying the several phenotypes of DYT24.

Method: Case series.

Results: A healthy 20-year-old female presented to the outpatient clinic due to gait impairment for 5 years. At the age of 15 she fell and twisted her ankle. A few months later she noticed her foot was deviated inwards when she walked. She denied any tremor, pain, weakness or spams. She was already on levodopa 150 mg daily, without improvement. On examination she had a dystonic posturing with inversion of her left foot when walking, with normal posture when at rest or walking backwards; her neurological examination was otherwise unremarkable. Her family history was striking for a father with cervical dystonia and parkinsonism, a grandfather with rapidly progressive cervical dystonia and myoclonus, and a younger brother with childhood myoclonic dystonia. A genetic panel of inherited forms of dystonia found the point mutation c.1787C>A (p.Ser596Tyr) in all afflicted patients.

Conclusion: Previously reported ANO3 mutations usually present with craniocervical dystonia, and rarely generalized or leg dystonia. Our kindred exemplify the heterogeneous presentation of this disorder, as well as a wide phenotypic variability within the same family.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotypic-segregation-in-kindred-with-a-novel-ano3-variant/