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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