Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. Early in the disease, affected individuals may have gait disturbance, slurred speech, difficulty with balance, brisk deep tendon reflexes, hypermetric saccades, nystagmus, and mild dysphagia. Later signs include slowing of saccadic velocity, development of up-gaze palsy, dysmetria, dysdiadochokinesia, and hypotonia. In advanced stages, muscle atrophy, decreased deep tendon reflexes, loss of proprioception, cognitive impairment (e.g., frontal executive dysfunction, impaired verbal memory), chorea, dystonia, and bulbar dysfunction are seen. Onset is typically in the third or fourth decade, although childhood onset and late adult onset have been reported. Those with onset over age 60 years may manifest a pure cerebellar phenotype. Interval from onset to death varies from ten to 30 years; individuals with juvenile onset show more rapid progression and more severe disease. Anticipation is observed. An axonal sensory neuropathy detected by electrophysiologic testing is common; brain imaging typically shows cerebellar and brain stem atrophy.
The diagnosis of SCA1 rests on the result of molecular genetic testing to detect an abnormal CAG trinucleotide repeat expansion in ATXN1. Affected individuals have alleles with 39 or more CAG trinucleotide repeats. Such testing detects 100% of cases.
SCA1 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the expanded allele. Prenatal diagnosis for at-risk pregnancies is possible if the diagnosis has been confirmed by molecular genetic testing in an affected relative; however, requests for prenatal testing of typically adult-onset diseases are not common.