Ethical Considerations in Neurogenetic Testing

Xiaowei W. Su, MD, PhD; Zachary Simmons, MD


Semin Neurol. 2018;38(5):505-514. 

In This Article

Abstract and Introduction


Recent advances in the genetics of neurologic diseases coupled with improvements in sensitivity and specificity are making genetic testing an increasingly important part of diagnosis and management for neurologists. However, the complex nature of genetic testing, the nuances of multiple result types, and the short- and long-term consequences of genetic diagnoses raise important ethical issues for the clinician. Neurologists must balance the ethical principles of beneficence and nonmaleficence, on the one hand, with patient autonomy on the other hand, when ordering such tests by facilitating shared decision making, carrying out their fiduciary responsibilities to patients, and ensuring that patients have adequate counseling to make informed decisions. This review summarizes ethical issues related to genetic testing for neurologic diseases, with a focus on clinical practice. Informed consent for genetic testing of patients and asymptomatic at-risk family members is discussed. The roles and responsibilities of physicians as genetic counselors are reviewed, including the framing of incidental findings and variants of unknown significance that impact individuals' decisions about whether to pursue genetic testing and what results they wish to know. Disclosure and its consequences for the patient are placed within an ethical framework to permit a better understanding of why genetic testing is different from most other diagnostic testing ordered by physicians. The review ends with clinical vignettes that attempt to place ethical principles into familiar clinical settings involving physicians, patients and their families.


Genetic testing is an increasingly important tool in the diagnosis and management of neurologic disorders. One of the first genetically characterized human diseases was Duchenne muscular dystrophy (DMD), a neuromuscular disorder linked to dystrophin gene mutations.[1] Since this milestone in the mid-1980s, next-generation techniques for clinical genome and exome sequencing (CGES) have become widely available, with costs that are decreasing exponentially. According to the latest National Human Genome Research Institute review performed in mid-2017, the current cost of one whole-exome sequencing (WES) analysis from sample collection to clinical interpretation is approximately $1,000.[2] In a recent analysis of the diagnostic yield of WES in 40 patients aged 3 to 70 years with suspected neurogenetic disorders, 16 patients (40%) achieved a full molecular diagnosis, including hemiplegic migraine, sporadic ataxia, congenital epilepsy syndromes, leukodystrophies, and mitochondrial disorders, among others. An average of 11.5 years elapsed between symptom onset and WES in this cohort, with an average per-patient cost of testing prior to WES of $1,650, which was 65% more than the $1,000 cost of WES.[3]

Though the speed, sensitivity, specificity, and clinical utility of genetic testing continue to improve, the risks and benefits must be evaluated carefully to best serve patients. Decision making to recommend genetic testing is complex and nuanced, and the results of such testing may have expected and unexpected short- and long-term consequences. This review addresses major ethical issues associated with genetic testing for neurologic disorders in symptomatic and asymptomatic at-risk (presymptomatic) individuals and their relatives. Topics are geared toward neurologists considering neurogenetic testing as part of diagnosis or management, so that clinicians may have informed discussions with patients and their families before testing and during follow-up. Illustrative, hypothetical case scenarios will be presented to address specific ethical issues that arise from genetic testing in selected diseases. Prenatal diagnosis and counseling is beyond the scope of this article and will not be addressed.