Family Medicine

The role of genetics—in researching, predicting, diagnosing, preventing, and treating rare and chronic illness—is dramatically expanding. Community asked leaders in genetic medicine what that means for you and your loved ones.

Since the 1990 initiation of the Human Genome Project to map the human genome, and its completion in 2003, the pace of genetic research has steadily accelerated. Most diseases have a genetic component, but, according to the CDC, “researchers have identified only a small fraction of the genetic component of most diseases.”

Perhaps nothing better illustrates the surge in public interest in genetics than the best-selling status of 2010’s “The Immortal Life of Henrietta Lacks,” in which author Rebecca Skloots compellingly chronicles the true story of Lacks, a young woman with cervical cancer, whose tumor cells were taken and cultured by a researcher, without her knowledge or permission.

Lacks died in 1951 at the age of 31, and in the six decades since, her tumor cells—which are “immortal,” and unusual in that, unlike most cells, they keep growing and multiplying in lab culture—have been used to establish the HeLa (for Henrietta Lacks) cell line. The HeLa cell line has helped researchers study and develop treatments for diseases including polio, cancer, hemophilia, AIDS, Parkinson’s disease, and leukemia, It’s estimated that more than 50 million metric tons of HeLa cells have been grown for use in invaluable lifesaving medical research worldwide since Lacks’ death.

Lacks’ family was unaware that the HeLa cells were being used for research until the 1970s. In August 2013, NIH and the Lacks family announced an agreement allowing biomedical researchers controlled access to the data gathered from study of the HeLa genome, and the Lacks family a role in the work being done. Researchers who use or generate data from HeLa cells will now be asked to include in their publications an acknowledgement and expression of gratitude to the Lacks family for their contributions.

Lacks’ story has generated so much interest that Oprah Winfrey plans to produce an HBO screenplay adaptation of the book. Beyond Hollywood, this prompts the question: How do genetics affect patients and families living with chronic and rare diseases?

Personal Power

Sharon Terry, President and CEO of the nonprofit health advocacy organization, Genetic Alliance, found herself drawn into genetic research advocacy when her own children were diagnosed with the rare genetic condition pseudoxanthoma elasticum (PXE) in 1994.

Their children’s diagnosis led Terry and her husband Patrick to found the research advocacy organization, PXE International, eventually resulting in the discovery of the gene associated with PXE. Terry recalled, “My husband and I felt that if we didn’t do something, nothing would be done.”

Terry believes that genetic research will have a profound impact on health care over the next decades. “We will have a much better understanding of disease,” she said. “We’re also going to be able to understand what role environment plays.”

“We all have some things in our genome that are not perfect. We believe that the individual needs to be empowered. We offer tools to help them deal with it,” Terry said, and tools to answer the question, “‘How do I get involved in research?’”

Genetic Alliance’s goal, Terry said, is “that we get better at finding ways of empowering people. We want treatments for all of these diseases. We want to accelerate people getting the services they need.”

Family History

When Venezuelan physician Americo Negrette arrived in San Luis, Venezuela in 1952 to begin his rural internship, he observed the uncontrolled movements and unsteady gait of many of the residents of several insolated, impoverished villages along the shores of Venezuela’s Lake Maracaibo. Negrette initially thought they were intoxicated. Locals called the condition “el mal de San Vito” (the sickness of St. Vitus).

Negrette was intrigued and began researching the illness among the local population. Through his studies, Negrette determined that “el mal” was in fact Huntington’s disease.

In 1968, psychoanalyst Milton Wexler founded the Hereditary Disease Foundation when his wife, Leonore, was diagnosed with Huntington’s disease. Four years later, Negrette’s colleague, Ramon Avila-Giron, presented a film about one of the Venezuelan HD villages to attendees of a Huntington’s disease symposium. The audience was astounded, having never before seen such a large concentration of Huntington’s patients. Leonore and Milton Wexler’s daughter, Nancy, was in the audience.

Leonore Wexler succumbed to Huntington’s disease in 1978. The next year, Nancy Wexler began a 20-year study of the families living around Lake Maracaibo. They would later become known as the world’s largest Huntington’s disease family.

Over the course of the next decades, Wexler and her team studied more than 18,000 residents of the area, mapping their vast family tree, and collecting more than 4,000 blood samples. They ultimately traced the gene’s origins in the region to one common ancestor, Maria Concepción Soto, who died from Huntington’s disease in 1880, and who might have inherited the HD gene from a European sailor who was her father.

In 1983, as a result of their research on the Venezuelan families, Wexler and her team discovered the location of the gene that causes Huntington’s disease, and in 1993 they isolated the Huntington’s gene.

The discovery of the HD gene led to the development of the HD test, which can determine whether pre-symptomatic individuals will develop the disease. The blood samples collected by Wexler have also helped map genes for diseases including familial Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and kidney cancer.

Today, modern genetic technology is helping treat communities whose ways of life are deeply rooted in tradition. Built and supported by Amish and Mennonite families, the Clinic for Special Children was founded in 1989 in Strasburg, Pennsylvania by D. Holmes Morton, M.D., and his wife, Caroline.

During Dr. Morton’s research fellowship at Children’s Hospital of Philadelphia, his diagnosis of an Amish boy’s illness led to the discovery of 16 other Amish children in the same community with the same rare disorder, known as “Amish cerebral palsy,” which was actually glutaric aciduria type 1 (GA1).

Learning that Amish and Menonnite children can be particularly vulnerable to certain genetic disorders, including alpha-1 antitrypsin deficiency and complex partial epilepsy, the Mortons decided to establish the Clinic for Special Children. The clinic is dedicated to researching and treating the rare diseases found in these communities, aiming to prevent disability and early death, and to do so locally and inexpensively, with state-of-the-art technology.

Community spoke with Kevin A. Strauss, M.D., Medical Director of the Clinic for Special Children about the clinic’s genesis and mission.

After the clinic set up local pediatric services, it very quickly became clear that a number of other diseases in this population would be amenable to this kind of approach. We deal with more than 140 rare genetic diseases, and we discover on average four genetic diseases every year.

We’re supported by, and here to serve, uninsured Amish and Mennonite patients. We’re trying to find the most robust, affordable and rapid technologies for our populations.

One of our guiding principles is that we’re continually trying to utilize biomedical diagnostics to deliver better services to patients. We have a Ph.D. molecular geneticist on staff and can do very affordable molecular testing.

For our alpha-1 patients, we do a 45-minute test for $50, using light scanner technology and thermocycling for high-res genotyping analysis. It’s a very simple DNA-based test, and it’s cheaper than doing serum enzyme testing. I don’t think a lot of people are using this technology.

Alpha-1 is more common in the Amish and Mennonite communities than what you would find in the general population. The Amish and Mennonites are what you call ‘founder populations.’ In the late 1600s, they began migrating from Switzerland to the U.S., but very few of them survived the voyage.

Approximately 100 couples are the sole genetic stock for the approximately 30,000 Amish in Lancaster County, Pennsylvania. They’re small gene pools for large populations. There is a higher incidence of some diseases within these populations, because carrier status gets carried on.

Complex partial epilepsy is not a single entity, but multiple different genes and it’s probably the fourth or fifth most common diagnosis in our patients.

There are different genetic risks based on ethnicity. There are also certain genetic diseases they don’t get. Cystic fibrosis, for example, is unheard of in Amish and Mennonite patients.

Although the Amish and Mennonite are averse to technologies that are divisive, like iPods, they are accepting of technologies that are life-affirming and beneficial to the children and the community. They are very willing to participate in clinical research. More than 70 published papers have come out of research that we have done here.

What I find most striking about the clinic is that it’s a model for traditional old-fashioned medicine, caring for the individual on a local, low-cost basis, during the most astonishing revolution in human biology. At no other time in modern medicine have we had this opportunity to determine a person’s health risk before they develop symptoms. All of that progress can be leveraged to benefit the patient. The communities we serve are providing us with lessons about how we can choose to use technology, and how our values guide our science.

The CDC reports that, “genetic tests have been developed for more than 2,200 diseases, of which 2,000 are currently available for use in clinical settings.” Community spoke with Rebecca J. Nagy, President of the National Society of Genetic Counselors about the importance of genetic counseling for those undergoing genetic testing.

What are the different types of genetic counseling?

Genetic counselors care for patients and families with a variety of conditions that cover the entire lifespan. Prenatal genetic counselors work with individuals who have concerns around a pregnancy that may be at increased risk based on family history, exposures or the mother’s age.

Pediatric genetic counselors work closely with physicians and see infants and children who may have a genetic condition. The physician works to obtain the correct diagnosis, and the genetic counselor is there to help the family understand what this diagnosis means for the child and the family, for future pregnancies and other family members.

Some genetic counselors work in the adult setting, seeing patients who have concerns about a family history of heart disease, cancer or other adult onset conditions. All of these clinical genetic counselors (prenatal, pediatric and adult) provide support and resources to the family while they are coping with and adjusting to their diagnosis.

Finally, there are many genetic counselors who work outside of the clinical setting. Some work in laboratories and serve as a conduit between the lab and physicians, helping them understand what specific test results might mean. Many genetic counselors are involved in research, public health or administration.

When should genetic testing for rare and chronic diseases be accompanied by genetic counseling, and why?

Learning that you or your child has a genetic condition can be difficult and emotional. It may also have implications for other family members.

By seeing a genetic counselor before testing, individuals and families can make an informed decision about whether testing is the right choice for them and can also be provided with information about the likelihood that their condition is hereditary and whether or not genetic testing would be helpful.

If genetic testing is ordered, genetic counselors can help the individual/family understand what the results mean for them and their family, and they can work together with the physician to make sure proper medical management recommendations and/or treatment plans are put in place.

Genetic counselors can also provide the family with support and resources to help them cope with the diagnosis, if necessary. For example, genetic counselors can help the family identify other families who have a child or family member with the same diagnosis and can identify advocacy and support groups that can provide ongoing information and support.

They can also coordinate referrals to other specialists and can be an ongoing resource if new developments are made in the field. Many of my patients will check back in with me each year to see if there is anything new that they should know about their diagnosis or the treatment for their condition.

What should patients, families, and caregivers look for when selecting a genetic counselor?

You can find a genetic counselor in your area by going to NSGC.org and clicking on the Find a Counselor tool. This provides a listing of board certified/board eligible genetic counselors.

Board eligible counselors have completed training at an accredited genetic counseling training program and are eligible to sit for their certification exam, which is offered twice a year. Board certified genetic counselors have also graduated from an accredited program and have passed this certification exam.

What tips can you provide for talking to family members about the need for genetic testing and counseling?

When approaching family members about the need for genetic counseling or testing, it is important to understand that not everyone in your family will want to undergo testing and counseling. And those that do undergo testing may not make the same decisions about what they wish to do with the information.

Sharing the information with family members and helping them find a genetic counselor is enough. Family members can then make their own choices about whether testing and counseling is right for them.

Many times, genetic counselors will provide patients with a family letter that explains what testing has been done, what it might mean for family members and how to find genetics professionals in their area. This is an easy way to communicate with family members and it takes the burden off of the patient to have to contact everyone by phone and have what may be a difficult or awkward conversation.

What role do you see genetic testing and counseling playing in medicine over the next 10 to 20 years?

The demand for genetic counseling and testing will continue to rise. Genetic testing is now a part of mainstream medicine and is already being used to help diagnose and treat diseases differently than we did even five to 10 years ago.

I see this trend continuing and expanding out into other areas. Given new testing technologies such as whole exome and whole genome sequencing, genetic tests are so much more complex, which makes the interpretation of test results more difficult. It will be critical for individuals and their families to have access to genetics professionals who can interpret this complex information for them.

Look for Part II of “Family Medicine” in the Spring 2014 issue of Community, featuring interviews with rare disease specialists, including Columbia University’s Wendy Chung, M.D., who discusses genetic research on pulmonary hypertension.

The Genetic and Rare Diseases Information Center (GARD)
Created by NIH in 2002 to help people find useful information about genetic and rare diseases, GARD provides immediate, virtually round-the-clock access to experienced information specialists who can furnish current and accurate information—in both English and Spanish.

GARD has information on:

• What is known about a genetic or rare disease
• What research studies are being conducted
• What genetic testing and genetic services are available
• Which advocacy groups to contact for a specific genetic or rare disease
• What has been written recently about a genetic or rare disease in medical journals

The Genetic and Rare Diseases Information Center (GARD)
P.O. Box 8126
Gaithersburg, MD 20898-8126
Toll-free: 1-888-205-3223
http://rarediseases.info.nih.gov/GARD
E-mail: [email protected]

Genetic Alliance
This nonprofit health advocacy organization is committed to transforming health through genetics and promoting an environment of openness. Genetic Alliance’s www.genesinlife.org website provides information about health and genetics. Genetic Alliance offers “Does It Run in the Family?” a free online booklet that families and communities can download at www.familyhealthhistory.org and customize to use in collecting family health history.

National Human Genome Research Institute
Communications and Public Liaison Branch
National Institutes of Health
Building 31, Room 4B09
31 Center Drive, MSC 2152
9000 Rockville Pike
Bethesda, MD 20892-2152
Tel. 301-402-0911
www.genome.gov/Patients

National Society of Genetic Counselors
330 N. Wabash Avenue, Suite 2000
Chicago, IL 60611
Tel. 312-321-6834
www.nsgc.org

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