How to Keep Pace With Genetic Advances in Movement Disorders
Interpreting Ambiguous Results
Another practical concern for neurologists is the interpretation of variants of unknown significance (VOUS) in genetic test results. “It means that a change or variant in the normal gene was discovered by the laboratory, but the change has never been described in association with the disease that you are interested in,” Dr. Jinnah said. “As a result, the laboratory cannot tell you whether it is relevant or not.”
Neurologists might be inclined to tell a patient that they “found something weird in their DNA,” but this approach “consolidates the patient’s concern that they have some mysterious disorder that none of the doctors can figure out, even the experts,” he said. Nor should neurologists tell a patient that the VOUS is not significant, because that is not what VOUS means.
A VOUS is comparable to a radiology report that says, “Clinical correlation is advised.” That phrase leads neurologists to compare neuroimaging to the clinical phenotype and ask whether the imaging findings make sense. “A VOUS is no different from this,” he said. Neurologists cannot explain all genetic variants, just as neurologists cannot explain all of the spots on a brain scan. “We have to get comfortable with the fact that we do not have answers for everything and that there will be some ambiguities when we are done.”
Genetics is logical and straightforward, and educational sessions are available at conferences for neurologists who are interested in learning more about genetic testing, Dr. Jinnah said. Neurologists also can refer patients to experts. “This referral must be a collaboration,” he said. “People in human genetics are not trained in movement disorders, and many of them have no formal training in neurology. They need your careful phenotypic exam to point them in th
Genetic testing often is expensive, not readily available, and not covered by insurance, but this situation may change, Dr. Jinnah said. He likened the situation of genetic testing today to that of MRI in the 1980s. “Only a few centers in the world had [MRI]. It was extremely expensive. Now, MRI scanners are everywhere, and everybody uses it because it is so valuable in clinical medicine,” he said. “I suspect that in a few years, we will see the same with genetic tests.”
—Jake Remaly
Suggested Reading
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Gahl WA, Tifft CJ. The NIH Undiagnosed Diseases Program: lessons learned. JAMA. 2011;305(18):1904-1905.
Olgiati S, Quadri M, Bonifati V. Genetics of movement disorders in the next-generation sequencing era. Mov Disord. 2016;31(4):458-470.
Sawyer SL, Hartley T, Dyment DA, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016;89(3):275-284.
van Egmond ME, Lugtenberg CHA, Brouwer OF, et al. A post hoc study on gene panel analysis for the diagnosis of dystonia. Mov Disord. 2017;32(4):569-575.
