Autosomal dominant ataxias
What are features of autosomal dominant ataxias?
Also referred to as spinocerebellar ataxias (SCAs), these disorders have common core features of cerebellar and brainstem signs and symptoms and dysfunction of associated pathways and connections.
Over 30 types are identified and grouped by shared mechanisms: polyglutamine expansions, ion-channel dysfunction, mutations in signal transduction molecules, and disease associated with noncoding repeats.
Although family history with an autosomal dominant inheritance pattern should heighten suspicion for an SCA, individual SCAs are difficult to distinguish based on clinical grounds.
Phenotypes may include pure cerebellar ataxia or ataxia with various comorbidities.
Anticipation, where subsequent generations manifest symptoms at an earlier age, is seen in polyglutamine expansions.
SCA3 is the most common worldwide. SCAs 1, 2, 3, 6, and 7 account for 50% of all dominant ataxias.
With onset >50 years, SCA6 and fragile X tremor/ataxia syndrome (FXTAS) are most frequent.