Another Twist in the Tale: Intrafamilial Phenotypic Heterogeneity in ANO3-Related Dystonia

Mutations in the anoctamin 3 (ANO3) gene cause autosomal dominant craniocervical dystonia (DYT24), presenting from childhood to mid-life. However, in the past years, the clinical spectrum of this disorder has widened. We present a family with heterogeneous presentation, exemplifying phenotypic diversity in DYT24.

The index case presented with myoclonic dystonia at age 10. His family history was remarkable for cervical dystonia with myoclonus in his grandfather, cervical and upper limb dystonia along with dopa-responsive parkinsonism in his father and lower-limb dystonia in his teenage sister. Magnetic resonance imaging and blood work-ups of all the affected family members were normal. The genetic panel for inherited forms of dystonia disclosed a point mutation c.1787C > A (p.Ser596Tyr) segregated in all affected family members.

ANO3 mutations usually present with craniocervical dystonia and rarely generalized or leg dystonia. This family exemplifies the heterogeneous presentation of this disorder as well as a wide phenotypic variability within the same family.