Genetic Testing to Transform Care

Improved diagnoses and guided treatment choices for neurological disorders

Fifteen years after the human genome was decoded, genetic testing is becoming more widely available and is taking its appropriate place in mainstream medicine. The genetic information that cost Steve Jobs more than $100,000 when he was fighting cancer five years ago1 is available today for less than $1,000. Yet, as with any technological advance, successfully realizing the promise of genomic medicine will require innovative approaches and a willingness to rapidly adapt to changes to ensure that clinically useful services are accessible to and implemented for the right individuals.

Clinicians and patients face a dizzying array of options when it comes to genetic testing, ranging from “recreational” genetic tests that provide insight into ancestry to simple screening panels for healthy individuals to highly advanced diagnostic tests used to guide personalized medicine. Costs are coming down; the number of genes with clear medical significance is going up; and education is needed across the board.

Cancer is among the first of many diseases that spring to mind when considering genetic testing. Genetic information helps diagnose cancer, understand tumor profiles and even predict potential at-risk patients. Alongside cancer, genetic testing has also made a significant impact in cardiology, rare diseases and neurology to name just a few. In fact, although eclipsed by cancer in terms of public awareness, the usefulness of genetic testing in diagnosing and treating neurological disorders promises to reshape how genetic testing informs healthcare in the next decade and beyond.

Disrupting the Diagnostic Odyssey

Neurological disorders with a genetic basis affect millions of people, and symptoms can present as early as at birth—or even prenatally. Because of the devastating outcomes of these disorders, it is important to get to an accurate diagnosis as early as possible, particularly for those suffering from rare, treatable forms. Some may result from metabolic defects while others from disrupted function of genes critical for early development and normal functioning of the nervous system. Neurological symptoms can be notoriously difficult to understand, and accurate diagnoses can be frustratingly elusive. Too often, young patients, their parents and their physicians find themselves on a diagnostic odyssey that lasts years and costs dearly in time, money, emotional toll and lost therapeutic opportunities.

A recent survey2 of 101 clinicians and 150 patients and caregivers in the rare disease community highlighted this challenge. Patients reported receiving an average of three preliminary diagnoses and seven diagnostic tests and/or procedures over an average of 3.9 years. During this time, 39% of patients felt they had paid for ineffective treatments or interventions that were based in part on an incorrect diagnosis.

Furthermore, clinicians’ responses suggested patients are actually underestimating the challenges to diagnosis. Clinicians reported that rare disease patients receive on average 4-5 diagnoses and 14 diagnostic tests and/or procedures during their diagnostic journey. Clinicians reported lack of information about genetic testing (54%) as an obstacle, agreeing that genetic testing is useful (83%) and shortens the time to diagnosis (69%).

Genetic testing can ameliorate this frustrating process through carefully curated gene panels constructed with the most up-to-date understanding of genetic variants and hereditary disease. Given the clinical overlap among many neurological disorders, comprehensive panel testing with excellent technical sensitivity allows for a more efficient evaluation of multiple conditions based on a single indication for testing.

Whole exome sequencing and chromosomal microarrays also have high diagnostic yield and, therefore, are essential tools for diagnosing rare pediatric developmental disorders. Identification of the molecular basis of disease in an affected individual can confirm diagnosis, predict prognosis and, in some cases, indicate possible therapeutic approaches. Once a diagnosis is made, sharing genetic information and testing of appropriate additional family members can potentially help improve outcomes for others as well.

The importance of genetic testing is not limited to rare neurodevelopmental disorders, however. Epilepsy is among the most common neurological disorders, affecting roughly 65 million people worldwide.3 Childhood-onset epilepsy tends to have a genetic etiology more often than adult-onset disease.4 A well-designed epilepsy panel analyzes all the major known genes  to provide a robust and cost-effective analysis of the most common genetic etiologies. This serves as a first test before moving onto more expensive and exploratory exome sequencing. In conjunction with a thorough clinical and family history, genetic testing can help move from an ambiguous epilepsy diagnosis to a precise one that can be carefully correlated and, thus, provide improved and appropriately tailored care for the patient—in some cases including more effective drug treatments.

Genetic information is most often used to find or firmly establish a clinical diagnosis, but using it to guide treatment is becoming increasingly common. Some examples of medical management guided by genetic diagnosis in neurological disorders include diet modification in certain forms of epilepsy and avoiding neurotoxic taxane or vincristine therapy in hereditary peripheral neuropathy. In fact, there are a significant number of treatments in late stage clinical trials that will expand the actionable utility of genetic testing. Such experimental therapies include exon skipping therapy for Duchenne Muscular Dystrophy and enzyme replacement therapy for CLN2-related Batten disease.

Accessing the Power of Genetic Testing

While there is ample reason to celebrate how far we’ve come in our understanding of genetic disease, personalized medicine is still very much at the starting line, and there are a number of hurdles to clear in order to fully realize the power of genetic medicine. The first challenge is to promote data sharing among clinicians and laboratories to improve our ability to interpret rare genetic variants, which are frequently encountered in genetic testing and have little-or-no available evidence to support or refute their connection to disease.

Medically responsible genetic testing should include sharing de-identified data to improve overall genomic healthcare for everyone. By sharing genetic information with public databases, such as ClinVar, laboratories have a mechanism for peer-review of their variant interpretations and can establish an appropriate gold standard for the highest quality genetic testing.

Even within those disorders in which heritability is well-understood, expert guidance is often needed because the results and implications that arise from genetic testing can be very complex. Therefore, a second challenge is to uniformly provide effective and accessible genetic counseling to help patients and their clinicians before, during and after testing. From logging a patient’s family history to interpreting results that can be complicated or confusing, genetic counselors serve as advocates and ambassadors of genetic medicine.

Finally, of course, there is the challenge of cost. Healthcare companies must remain committed to driving down the cost of testing while providing the highest quality testing first and foremost. Additionally, Insurers’ understanding of the role that genetic testing can have in reducing overall costs and burden of disease is equally essential to increasing the accessibility of genetics to everyone. A transparent approach to pricing represents an important model for 21st century healthcare overall and is essential in the genetics market.

Improved healthcare for millions is possible if we as a healthcare community continue to adapt, innovate and appropriately integrate genetics into personalized medicine.


  1. Regalado, A, “Steve Jobs Left a Legacy on Personalized Medicine.” MIT Technology Review.
  2. Gandomi S, Hooker G, Sweeney B, Stueland K, Aradhya S, Esplin E. “Rare disease diagnosis obstacles: patient perspectives and physician findings.” Poster presented at: American College of Medical Genetics Annual Clinical Genetics Meeting. March 8-12, 2016, Tampa, FL. Abstract 443.
  3. Epilepsy Foundation, Epilepsy Statistics.
  4. Pal DK, Pong AW, Chung WK. “Genetic evaluation and counseling for epilepsy.” Nat Rev Neurol. 2010 Aug, 6 (8):445-53.

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