Thursday, January 21, 2016

Genetic testing for SCA (Spinocerebellar Ataxias)


Genetic testing for SCA has exploded in the past decade (2) (6) (4). More than a dozen SCA genes can now be tested through commercial labs, and the number seems to grow every year.

There are five distinct scenarios in which gene testing can be used by clinicians: diagnostic testing, predictive testing, prenatal testing, carrier testing, and risk factor assessment. In reality, however, only diagnostic and predictive testing concern the practicing neuro-ophthalmologist or neurologist. Gene tests are a powerful new addition to our diagnostic arsenal; we use them primarily to achieve an accurate diagnosis in a patient with specific neurologic symptoms.

A gene test does not differ much from testing blood chemistry profiles to establish a medical diagnosis. A positive test result, however, carries profound implications for patients and their families. Thus, genetic testing should be performed only after the patient has been counseled on the potential consequences of the results, both positive and negative. Once a genetic diagnosis is made in a symptomatic patient, we may be asked to assist other family members in obtaining predictive testing (screening for a mutation in someone who is at risk for a familial disease). Handling such queries from patients and their families is an unavoidable part of modern medicine. Web sites that provide useful updated information on genetic diseases, genetic tests, genetic counseling and the human genome include
Www.genetestsorg , the most useful site, contains frequently updated reviews of neurogenetic disorders and searchable lists of testing labs with contact information.
The primary benefit of diagnostic genetic testing is that it may provide a specific and accurate diagnosis. For example, an SCA gene test in a patient whose symptoms are consistent with a genetic form of ataxia, but whose family history is uncertain or absent, can confirm the clinical diagnosis with efficiency, economy, and certainty. In an ataxic patient, gene tests are sensitive and specific, whereas brain MRI is not. In SCAs, gene testing can specify a diagnosis from among a group of clinically similar genetic conditions. Even when a condition is currently incurable, as with the SCAs, establishing a specific diagnosis can put an end to the quest for an accurate diagnosis, permit an informed discussion of the prognosis and available treatments, and facilitate discussions of genetic risk to other family members. The psychological lift of simply putting a name to a previously mysterious disease, even if there is no cure, should not be underestimated for some patients.


Current commercially available genetic test “panels” include only the most common (SCA1, 2, 3, 6, and 7) and some less common (SCA 5, 8, 11, 10, 12, 13, 14 and 17), comprising 75% of the known SCA genes. Whereas a positive gene test for a specific SCA establishes the diagnosis, an entirely “negative” SCA gene test panel does not exclude a hereditary ataxia. Accordingly, physicians must take great care in conveying the significance of negative gene test results to their patients. When a person’s ataxia has slowly progressed over 10 years and is symmetrical in its clinical and radiographic features, the disease very likely has a genetic basis whether or not the genetic panel detects it. In the absence of a family history of ataxia, an autosomal recessive cause is probably more likely than an autosomal dominant cause. The most common recessive ataxia is Friedreich ataxia, for which genetic testing is highly sensitive and specific (7).

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