Knowing your exact genetic diagnosis does more than just satisfy your curiosity — it can impact family planning, disease management and participation in clinical trials
Respondents to MDA’s Transitions Survey — in other words, people with a neuromuscular disease who are in their teens through late 30s — made it clear they had questions about the genetics of their disease, as well as questions about family planning and the value of diagnostic testing.
MDA’s Genetic Counseling Webinar, which occurred Feb. 22, 2012, answers many of those questions.
The hourlong webinar provided an overview of the general principles of clinical genetics — the branch of genetics concerned with the diagnosis, prognosis, management and prevention of genetic diseases. Also discussed were the ways in which genetic testing plays an important role in the ongoing treatment and management of neuromuscular disease.
The two genetic counselors who led the webinar each have extensive experience counseling families affected by neuromuscular diseases.
Joline Dalton is executive director of the Paul and Sheila Wellstone Muscular Dystrophy Center at the University of Minnesota, and the primary genetic counselor for the MDA clinics in the Twin Cities. She serves on the MDA Clinical Advisory Committee and the American Board of Genetic Counseling Credential Exams Committee.
Lisa Dellefave-Castillo is a genetic counselor with the Department of Medicine Section of Cardiology at the University of Chicago, where she sees individuals with inherited cardiovascular diseases, and those with neuromuscular diseases with cardiac involvement.
Dellefave-Castillo began with a detailed explanation of cells, chromosomes, the function of genes and proteins, and what happens when something goes wrong at this level.
A genetic test looks for a change in a gene, chromosome or protein that will give information about the chance of having a genetic condition or having a child with a genetic condition, Dellefave-Castillo explained. Other less-accurate forms of testing include a physical exam, a measure of the level of enzyme creatine kinase, and/or a muscle biopsy.
Knowing your exact genetic diagnosis has advantages in terms of family planning and testing of other family members who may be presymptomatic, or may be carriers of the genetic mutation. An exact diagnosis also improves clinical management by alerting doctors to associated health problems, such as cardiac issues.
Sometimes, knowing your exact diagnosis is required for inclusion in clinical trials. Dellefave-Castillo illustrated this by pointing to Duchenne muscular dystrophy (DMD) research. The experimental therapy ataluren (formerly called PTC124) is in clinical trials for DMD caused by a stop codon mutation. Exon skipping, another promising DMD therapy currently in clinical trials, is targeted to very specific mutations in sections of the gene (exons).
Although these and therapies in other diseases are still in the future, "what can you do now?" Dellefave-Castillo asked rhetorically. "Get a genetic diagnosis to be ready for upcoming clinical trials."
Dellefave-Castillo and Dalton also delved into the complicated topic of inheritance, discussing X-linked, autosomal dominant and autosomal recessive inheritance patterns.
A number of diseases can be either autosomal dominant or autosomal recessive, depending on the mutuation. This includes (but isn’t limited to) limb-girdle muscular dystrophy (LGMD), Charcot-Marie-Tooth disease (CMT), congenital muscular dystrophy, some forms of congential and distal myopathy (see "other myopathies"), and some inherited forms of ALS.
For example, in the autosomal dominant and autosomal recessive forms of LGMD, it’s important to know your genetic diagnosis to know whether your heart can become involved and if so, to treat early with medications to slow progression and prevent sudden death, Dellefave-Castillo said.
What happens at a genetic counseling session?
A counselor will take family history, coordinate genetic testing, do risk assessment for family members, explain genetic testing results and explain inheritance patterns. Even though you’ve discussed your disease with your physician, genetic counselors can field additional questions, particularly those related to disease impact.
What are the limitations to genetic testing?
Currently there is no single test to identify all genetic causes of genetic disease. For now, clinicians must decide on testing options on a gene-by-gene and lab-by-lab basis, the presenters said. Additionally, not all results are easy to interpret.
In one example, a woman initially was told her genetic diagnosis was CMT, based on the presence of an unusual DNA sequence in one of the CMT-causing genes. However, the sequence turned out to be a normal variant, not a CMT-causing one. The bottom line: "You can't always rely on the initial test results," warned the webinar presenters.
What does it cost?
The cost of a genetic test ranges from $250 to more than $20,000. Will insurance cover it? It depends on the plan; private insurance often requires documentation of medical necessity. Medicare has an approved list of genetic tests. Very few institutions accept Medicaid to cover genetic testing.
When should unaffected family members be tested?
Testing can help with assessing risk for future offspring, and also warn of future medical risks. When no symptoms are evident, different institutions have different policies regarding the age-appropriateness of childhood testing.
"Back in the day, everyone had carrier testing once their brothers had been diagnosed," Dalton said, noting that now "it is really up to the parents to see if it is appropriate and when it is most helpful. The point where a son or daughter is asking questions might be a good time to discuss testing."
What is GINA?
The Genetic Information Nondiscrimination Act prevents discrimination in health insurance and employment for people with a diagnosis of a genetic disease. However, the Act does not cover life insurance. The participants advised that it's probably best to get your life and disability insurance first, before obtaining genetic testing.
How can I find a genetic counselor who is familiar with my disease?
Talk to your MDA health care services coordinator or clinic team for a recommendation.
The Genetic Counseling Webinar is one of several MDA-hosted webinars available for public viewing, covering research, health and daily-living independence.