What is spinocerebellar ataxia?

Risk Factors

The only risk factors are a known gene mutation or a family history of SCA. The SCAs can occur in all ethnicities, although some occur at a higher frequency among certain ethnic backgrounds, possibly due to a founder effect. Some SCAs are incredibly rare and have been identified only in a single family of one particular ethnic background. Men and women are equally likely to be affected. There is an average age of onset for each type of SCA, with onset in childhood or young adulthood, while others may not occur until late in life.

Etiology and Genetics

Each of the numerous SCAs is inherited in an autosomal dominant manner and has a distinct genetic cause, although the exact gene has not been identified for all. First-degree relatives of an affected individual are at a 50 percent risk to develop the same type of SCA. Some SCAs result from single point mutations, but many are trinucleotide repeat expansion disorders causing variation in age of onset, severity, and disease course exhibited among family members with the same disorder. Certain genes have a set number of repeating trinucleotides, but in some SCAs, the number of these repeated trinucleotides has expanded, causing an unstable gene. For those individuals who have a number of trinucleotide repeats within the reduced penetrance range, it is not possible to predict whether or not SCA will develop. Anticipation is common with some of the SCAs, meaning the number of trinucleotide repeats in an already unstable gene will continue to expand in future generations into the full mutation range. The condition will likely develop if the individual with a full mutation lives long enough. Signs and symptoms may occur at earlier ages of onset and with greater severity in succeeding generations due to anticipation. Family history may appear negative because of reduced penetrance, late onset, or early death of relatives. New gene mutations that are not inherited are also possible but rare.

Machado-Joseph disease (SCA3) is the most common SCA, and combined with SCA1, 2, and 6 is responsible for at least 50 percent of all autosomal dominant ataxias. It is estimated that 1 to 5 in 100,000 individuals are affected with an SCA.

While the exact function of each gene and its associated protein is unknown, it appears that the abnormal protein causes nerve cell damage in the brain and spinal cord. Current research focuses on understanding the effect of these gene mutations on the brain and further characterization of each SCA.

Symptoms

All types of SCAs include ataxia. Loss of coordination leads to difficulty with balance and walking, and to clumsiness of the hands. Speech may become slurred, and swallowing may become increasingly difficult. Visual disturbances and eye movement abnormalities are possible. Some SCAs have characteristic features that may aid in diagnosis, such as cognitive impairment, neuropathy, hearing loss, seizures, parkinsonism, other abnormal movements, or specific neurological signs detected on exam. It is essential to see a physician when symptoms interfere with daily activities, injury occurs after a fall, or swallowing becomes difficult.

Screening and Diagnosis

Family history, neurological exam, brain MRI, and genetic testing are all useful in diagnosis. The MRI may reveal cerebellar atrophy, or loss of tissue, common to all SCAs, in addition to spinal cord or brain stem atrophy. Only genetic testing can establish a diagnosis of a specific SCA, although testing is not available for every known type. Other clinical studies may be necessary to detect neurological findings characteristic of some SCAs.

Treatment and Therapy

There are no cures or specific treatments, although assistive devices and therapy may be beneficial. Medications may help alleviate some features, but individual response varies.

Prevention and Outcomes

Diagnostic genetic testing can help to provide an accurate diagnosis in affected individuals. With a known familial mutation, predictive genetic testing is available to determine whether an unaffected individual has inherited the gene mutation and will develop SCA.

There is no known prevention. Prenatal diagnosis and preimplantation genetic diagnosis may be possible with known familial mutations.

Some SCAs have a slowly progressive course and normal life span, but many progress more rapidly, with ten to twenty years passing from onset until extensive assistance with activities of daily living is required.

Bibliography

Ashizawa, Tetsuo, et al. "Clinical Characteristics of Patients with Spinocerebellar Ataxias 1, 2, 3, and 6 in the US; A Prospective Observational Study." Orphanet Journ. of Rare Diseases 8.1 (2013): 1–22. Print.

Di Gregorio, Eleonora, et al. "ELOVL5 Mutations Cause Spinocerebellar Ataxia 38." American Journ. of Human Genetics 95.2 (2014): 209–17. Print.

Manto, Mario, et al. Handbook of the Cerebellum and Cerebellar Disorders. New York: Springer, 2013. Print.

Nussbaum, Robert L., Roderick R. McInnes, and Huntington F. Willard. Thompson and Thompson Genetics in Medicine. 7th ed. New York: Saunders, 2007. Print.

Pulst, Stefan. Genetics of Movement Disorders. San Diego: Elsevier Science, 2003. Print.

Watts, Ray, and William C. Koller. Movement Disorders: Neurologic Principles and Practices. 2d ed. New York: McGraw, 2004. Print.