FDA Clearance of DTC Genetic Test Gets Mixed Reviews

Ricki Lewis, PhD

February 20, 2015

On February 19, the US Food and Drug Administration (FDA) authorized 23andMe to market a direct-to-consumer (DTC) carrier test for Bloom syndrome. The agency's decision to classify such carrier screening tests as class II medical devices, and exempting them from premarket review, may pave the way for a return of DTC genetic testing. The decision and the open door, however, have garnered mixed reviews from genetic counsellors and clinicians.

"This is the first step in our commitment to returning health information to our customers. Because this process was successful, we may be able to submit some future submissions through the standard 510(k) pathway," a spokesperson for 23andMe, based in Mountain View, California, told Medscape Medical News

FDA had banned the company from DTC marketing of genetic tests with a warning letter sent November 22, 2013, claiming that their "Personal Genome Service," termed "information," violated the Federal Food, Drug and Cosmetic Act. The company was selling the service without submitting evidence of accuracy, reliability, and clinical meaning.

Pros and Cons of DTC Genetic Testing

Genetics professionals had mixed reactions to the news.

"The greater impact is not in returning carrier testing for Bloom syndrome specifically, but in laying the framework for reporting carrier status of all single gene recessive conditions," said Joshua Petrikin, MD, director of Neonatal Genomics at the Center for Pediatric Genomic Medicine at Children's Mercy Kansas City, Missouri. "This is a useful step in empowering consumers with knowledge of their genetic predispositions and beneficial as a starting place for patients' discussions with their physicians."

Joy Larsen Haidle, MS, president of the National Society of Genetic Counselors and genetic counselor at the Humphrey Cancer Center in Minneapolis, Minnesota, disagreed. "This new policy is a slippery slope and might unwittingly set a dangerous precedent. Why not just add a bunch of other genes? Genetic testing is not a one-size-fits-all option," she told Medscape Medical News.

Leading up to the February 19 announcement, FDA required 23andMe to conduct multiple tests of accuracy and for the ability of consumers to understand the instructions and collect saliva samples. If the product is offered over-the-counter, labels on test kits must explain what results mean and provide information for contacting a genetics professional.

Robert Marion, MD, pediatrician and chief of the Division of Genetics at The Children's Hospital at Montefiore and developmental pediatrician at the Albert Einstein College of Medicine, New York, New York, has concerns that packaging requirements are not enough. "There's a reason entire fields, like genetic counseling and clinical genetics, have grown up over the past 50 years: genetic testing is not a simply 'black-or-white' issue of yes, you are a carrier of this mutation or no, you are not a carrier."

For example, Dr Marion pointed to interpretation of results, informing relatives, and misunderstanding as areas of potential concern.

Even some physicians have little experience with genetic testing, he said, relating the case of a couple considering terminating a pregnancy because one of the partners was found to be a carrier for Tay-Sachs disease. "Neither the obstetrician who ordered the test nor the couple understood that in order to have a child with Tay-Sachs, both parents needed to be carriers. Testing without the involvement of a professional is going to cause problems."

Bloom Syndrome and Cancer Predisposition

Bloom syndrome is one of the "Jewish genetic diseases" offered in test panels. JScreen, for example, a not-for-profit organization that is part of Emory University in Atlanta, Georgia, offers a 19-disease screen. Patients collect their saliva and mail the sample to a CLIA-certified laboratory, which notifies genetic counselors at Emory. The counselors, in turn discuss the results with patients, either by phone or in person.

The disease came to the United States from families in southeastern Poland and southwestern Ukraine between the 1300s and 1600s. Today the carrier rate is 1 in 107 among Ashkenazi Jews in the United States, according to information from 23andMe, but 1 in 37 among those who are of Polish descent.

Bloom syndrome is caused by mutation of the BLM gene, which results in DNA helicase deficiency and chromosome breakage. The syndrome includes growth retardation, red skin lesions on the face in a butterfly pattern, impaired immunity, digit anomalies, and predisposition to cancer, particularly lung cancer and leukemia. The young are especially photosensitive, and upper respiratory tract infections may be life-threatening. Most people with Bloom syndrome die of cancer in their teens or twenties.

Carrier testing for Bloom syndrome has advantages: It provides information on reproductive options, such as prenatal diagnosis, and it is actionable if parents identified as carriers have a child who has the syndrome. They can avoid excessive exposure to sunlight, certain chemotherapies, and x-rays and have frequent cancer examinations and tests, which can minimize disease severity in the child.

Limitations and Uncertainties of Testing

Although Bloom syndrome is relatively well known among genetics professionals, the FDA announcement left some experts puzzled and wary. Some note, for example, that the FDA did 'not indicate whether the whole gene will be sequenced or only the common Ashkenazi mutation detected, nor why Bloom was selected to go first.

Moreover, customers might not know that Bloom syndrome is just one of several Jewish genetic diseases. "If a consumer doesn't know enough of the big picture and only tests for Bloom syndrome, they are missing valuable information that might have impacted their family planning decisions. I'm perplexed by selection of this one gene," said National Society of Genetic Counselors president Haidle. Yet consumers who know more might assume that the carrier state itself increases cancer risk, as it does for other inherited cancer syndromes, she added, such as ataxia-telangiectasia.

Another subtlety of carrier testing for Bloom syndrome is that disease prevalence is lower than what the high carrier rate suggests. This indicates that penetrance may be low: even though the risk to offspring of inheriting two mutations from carrier parents is 25%, the empiric risk of developing the syndrome is actually less.

Distinguishing Carrier Tests From Other Genetic Tests

Several people interviewed agreed that a type of genetic disease for which DTC testing would never be appropriate is a predictive test for a late-onset dominant condition without treatment or prevention options, such as Huntington disease (HD).

"I think it would be challenging to offer predictive genetic testing DTC because of the nuances involved in the interpretation of the test results and understanding of risk," said Beth Tarini, MD, MS, an assistant professor of pediatrics at the University of Michigan, Ann Arbor. Predictive testing for conditions that are less definitive than HD, or involve multiple genes, could be even more confusing to consumers without genetic counseling, she added.

Dr Petrikin thought the choice of Bloom syndrome makes sense because it is relatively benign and rare. "This is important because the DTC product is not diagnosing active disease, but reporting a possible predisposition for a rare condition in offspring of the consumer."

Carol J. Saunders, PhD, director of the Molecular Genetics Laboratory at Children's Mercy, agreed. "This seems like a good middle ground for 23andme and the FDA. They have focused on a relatively low-risk situation to see how things go. Such testing, no matter how simple, still requires careful genetic counseling."

The benefits may go beyond the single gene test, according to Dr Tarini. "If increased access to this testing helps to motivate individuals to learn about their reproductive risks, then I think it offers health care providers a chance to better educate the public about genetics and their health — which is always a good thing."

A spokesperson for 23andMe told Medscape Medical News that the FDA clearance for the Bloom syndrome test is just a first step. "We will not report Bloom syndrome test results to 23andMe customers until we complete the regulatory process on additional tests and can provide a more comprehensive health product offering to customers," the company spokesperson said.

The people interviewed have disclosed no relevant financial relationships.

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