SNP Shot: Genomic Insights

Spinocerebellar ataxia type 2 (SCA2) is a progressive disorder affecting movement. Initially, individuals with SCA2 experience difficulties with coordination and balance, known as ataxia. Other early symptoms include various movement problems, trouble speaking and swallowing, and weakness in the eye muscles (ophthalmoplegia). This eye muscle weakness results in involuntary eye movements, including back-and-forth movements (nystagmus) and slowed rapid eye movements (saccadic slowing).

As SCA2 progresses, individuals may develop peripheral neuropathy, characterized by loss of sensation and weakness in the limbs. They may also experience muscle atrophy, involuntary muscle contractions (dystonia), and uncontrolled jerking movements (chorea). Some individuals develop parkinsonism, a group of movement problems including slow movement (bradykinesia), tremors, and muscle rigidity. Cognitive difficulties, such as short-term memory problems, impaired planning and problem-solving abilities, or overall cognitive decline (dementia), can also occur in individuals with SCA2.

The onset of SCA2 symptoms typically occurs in middle age, but can range from childhood to late adulthood. The average survival time for individuals with SCA2 is 10 to 20 years after the first symptoms appear.

Inheritance:

SCA2 is inherited in an autosomal dominant manner. This means that having only one copy of the mutated gene in each cell is enough to cause the condition. Most individuals with SCA2 inherit the mutated gene from an affected parent. However, some individuals may develop SCA2 even if neither parent has the condition. Individuals carrying an increased number of CAG repeats in the ATXN2 gene without showing SCA2 symptoms themselves are still at risk of passing the disorder to their children. The length of the CAG repeat sequence in the ATXN2 gene tends to increase with each successive generation. Longer repeats are usually associated with earlier symptom onset. This phenomenon, known as anticipation, is more frequently observed when the ATXN2 gene is inherited from the father (paternal inheritance) compared to inheritance from the mother (maternal inheritance).