SCA1

SCA1, or spinocerebellar ataxia type 1, is a dominantly inherited neurodegenerative disorder within the spinocerebellar ataxias caused by a CAG trinucleotide repeat expansion in the ATXN1 gene. It is part of the polyglutamine disease group and is characterized by progressive cerebellar dysfunction leading to gait and limb ataxia, dysarthria, and related symptoms.

Clinical features typically begin in adulthood, often in the 30s to 50s. Early signs include gait instability, limb incoordination, dysarthria, intention tremor, and nystagmus. As the condition advances, balance problems, worsening ataxia, and additional oculomotor abnormalities may appear; pyramidal signs can emerge later in the disease. Cognitive impairment is uncommon in many cases but may occur in later stages.

Genetically, SCA1 is caused by an autosomal dominant expansion of CAG repeats in ATXN1, resulting in a polyglutamine-expanded ataxin-1 protein. The repeat length correlates with age at onset and disease severity. Normal alleles typically range up to the mid-30s repeats, while pathogenic alleles are usually above 39 repeats. Anticipation can occur as repeats expand in successive generations.

Diagnosis is established by genetic testing for ATXN1 CAG repeat length. Neuroimaging, particularly MRI, often shows cerebellar and brainstem atrophy that may progress over time.

Management is supportive and multidisciplinary, focusing on mobility, speech, and daily functioning. Physical therapy, occupational therapy, and speech therapy are commonly used, with symptomatic treatment for spasticity or neuropathic symptoms as needed. There is no proven disease-modifying therapy; prognosis varies with repeat length and overall health, but the disease generally follows a slowly progressive course over years to decades.