SCAs

SCAs, short for spinocerebellar ataxias, are a group of inherited neurodegenerative disorders characterized by progressive cerebellar ataxia, frequently accompanied by additional neurological signs. Most SCAs are autosomal dominant, and the condition comprises more than 40 distinct genetic subtypes described to date.

Genetically, SCAs arise from a variety of mutations. Many subtypes are caused by CAG trinucleotide repeat expansions that produce proteins with long polyglutamine tracts (polyQ), leading to neuronal dysfunction. However, not all SCAs are polyQ disorders; some result from other mutation types.

Clinical features include insidious onset of gait instability and limb incoordination, with dysarthria, oculomotor abnormalities such as nystagmus, and tremor. Pyramidal signs and extrapyramidal features may accompany the ataxia in some subtypes. Onset can range from adolescence to late adulthood, and progression is variable.

Diagnosis relies on clinical assessment and family history. Genetic testing using panels or targeted testing identifies the specific SCA subtype. Neuroimaging, typically MRI, often shows cerebellar atrophy and brainstem involvement, helping to exclude mimicking conditions.

Management is supportive and multidisciplinary, as there is no cure to date. Rehabilitation therapies—physical, occupational, and speech therapy—aim to maintain function and communication. Symptom-directed treatments address spasticity, tremor, and other manifestations. Genetic counseling is advised due to dominant inheritance.

Epidemiology varies by population, with certain subtypes more prevalent in specific regions; for example, SCA3 (Machado-Joseph disease) is common in some populations. Ongoing research seeks disease-modifying therapies and a clearer understanding of genotype–phenotype relationships.