ANO3-related tremulous dystonia: case report

A 21-year-old woman presented with a severe tremor and involuntary spasms in her hands. Her tremor started at the age of seven, and while it was initially mild and only in bilateral upper extremities, its severity increased over time. There is no consanguinity between her parents, and her early developmental milestones are consistent with her age. Her father had involuntary movements with similar semiology. The neurological examination revealed a mild intellectual disability, head titubation, postural and action tremors, and dystonia affecting the bilateral distal upper extremities. Brain magnetic resonance imaging and investigations for neurometabolic diseases were normal. Exome sequencing analysis revealed a heterozygous likely pathogenic variant of ANO3 gene ([NM_031418.4]:c.1943A>G p.[Asn648Ser]), and she was diagnosed with ANO3-related dystonia (DYT-ANO3). She was started on trihexyphenidyl, and at the follow-up, partial improvement in her involuntary movements was observed.DYT-ANO3 caused by pathogenic variants of ANO3 gene were first described in families affected by adult-onset tremulous craniocervical dystonia, and since then, the phenotypic spectrum has expanded significantly. The onset of clinical features may vary from the first months of life to adulthood, and cases may present with a wide range of clinical spectrum, from focal/segmental to generalized dystonia, and from isolated to tremulous or jerky dystonia. Cases with the same genotype may present with movement disorders of different characteristics, suggesting that there is no definitive genotype-phenotype correlation in DYT-ANO3 cases. Additionally, cases with nondystonic features, such as nondystonic tremor, myoclonus and/or neurodevelopmental delay have also been reported.