Spinocerebellar ataxia type 3, also known as Machado-Joseph disease, is the most common form of hereditary spinocerebellar ataxia . Features include lack of coordination and balance, gait abnormalities, vision problems such as nystagmus and ophthalmoplegia, dysphagia, and dysarthria. Parkinsonism develops over time including spasticity, rigidity, dystonia, and tremor. Peripheral neuropathy, muscle weakness, and fasciculations may occur. Average age of onset ranges form the teens to the 40s, and lifespan is typically reduced.
SCA3 is inherited in an autosomal dominant pattern, and it is caused by a CAG trinucleotide repeat expansion in the ATXN3 gene. Repeat ranges are as follows: Normal (≤ 44), Intermediate (45-59), Pathogenic (≥ 60). Intermediate alleles may have incomplete penetrance, and the age of onset and rate of progression correlate with the size of the expansion.