SNP Shot: Genomic Insights

Spinocerebellar ataxia type 3 (SCA3) is a disease that causes increasing difficulty with movement. Individuals with SCA3 typically first notice issues with coordination and balance, a condition known as ataxia. Other initial indicators of SCA3 can include trouble speaking, involuntary muscle contractions (dystonia), muscle stiffness (spasticity), rigidity, tremors, protruding eyes, and double vision. Sleep disturbances, such as restless legs syndrome (RLS) or REM sleep behavior disorder (RBD), may also occur. RLS involves uncomfortable sensations in the legs and a strong urge to move them for relief. RBD involves physical activity during REM sleep, leading individuals to act out their dreams. Both RLS and RBD often result in daytime fatigue.

As SCA3 progresses, individuals might experience numbness and weakness in their arms and legs (peripheral neuropathy), muscle cramps, involuntary muscle twitching (fasciculations), and difficulty swallowing. Cognitive functions such as memory, planning, and problem-solving can also be affected.

The symptoms of SCA3 typically manifest during middle age, but can appear at any point between childhood and late adulthood. Eventually, those affected by SCA3 will need to use a wheelchair. Survival after the initial appearance of symptoms is usually between 10 and 20 years.

Inheritance:

SCA3 is inherited in an autosomal dominant manner. This means that only one copy of the mutated gene in each cell is necessary to cause the disorder. Generally, an affected person will have one parent who also has SCA3. The length of the CAG repeat sequence within the altered ATXN3 gene often increases as it is passed down through generations. A greater number of CAG repeats tends to correlate with an earlier onset and more rapid progression of symptoms. This phenomenon is known as anticipation. Anticipation may be more noticeable when the altered ATXN3 gene is inherited from the father (paternal inheritance) rather than the mother (maternal inheritance). Rarely, individuals may inherit expanded CAG repeats on both copies of the ATXN3 gene. These individuals tend to exhibit more severe symptoms, and the onset of the condition usually occurs in childhood.