Genetics and Health - Genetic Testing In Children And Adults
disease screening risk treatment
Genetic testing also can be performed postnatally (after birth) to determine which children and adults are at increased risk of developing specific diseases. Scientists can perform predictive genetic testing to identify which individuals are at risk for cystic fibrosis, Tay-Sachs disease, Huntington's disease, amyotrophic lateral sclerosis (ALS; a degenerative neurologic condition commonly known as Lou Gehrig's disease), and several types of cancers (including some cases of breast, colon, and ovarian cancer).
A positive test result (the presence of a defective or altered gene) from predictive genetic testing does not guarantee that the individual will develop the disease; it simply identifies the individual as genetically susceptible and at increased risk for developing the disease. For example, a woman who tests positive for the BRCA1 gene has about an 80% chance of developing breast cancer before age sixty-five. It is also important to note that like other types of diagnostic medical testing, genetic tests are not 100% predictive—the results rely on the quality of laboratory procedures and accuracy of interpretations. Further, because tests vary in their sensitivity and specificity, there is always the possibility of false-positive and false-negative test results.
Researchers hope that positive test results will encourage people at higher-than-average risk of developing a disease to be especially vigilant about disease prevention and screening to detect the disease early, when it is most successfully treated. There is an expectation that genetic information will increasingly be used in routine population screening to determine individual susceptibility to common disorders such as heart disease, diabetes, and cancer. Such screening will identify groups at risk so that primary prevention efforts such as diet and exercise or secondary prevention efforts such as early detection can be initiated.
Symptomatic Genetic Testing
Most genetic testing is performed on persons who are asymptomatic to determine if they are carriers or to identify susceptibility or risk of developing a specific disease or disorder. There is, however, some testing performed on persons with symptoms of a disease in order to clarify or establish the diagnosis and calculate the risk of developing the disease for other family members. This type of testing is known as diagnostic genetic testing, predictive genetic testing, or symptomatic genetic testing. It determines the likelihood that a healthy person with a family history of a disorder will develop the disease. Testing positive for a specific genetic mutation indicates an increased susceptibility to the disorder but does not establish the diagnosis. For example, a woman may choose to undergo testing to find out whether she has genetic mutations that would indicate the likelihood of developing hereditary cancer of the breast or ovary (BRCA1 and BRCA2, respectively). If she tests positive for the genetic mutation, she may then decide to undergo some form of preventive treatment. Preventive measures may include increased surveillance such as more frequent mammography, chemoprevention—prescription drug therapy intended to reduce risk—or surgical prophylaxis, such as mastectomy (surgical removal of one or both breasts) and/or oophorectomy (surgical removal of one or both ovaries).
This type of testing also may assist in directing treatment for symptomatic patients in whom a mutation in a single gene (or in a gene pair) accounts for a disorder. Cystic fibrosis and myotonic dystrophy (the most common adult form of muscular dystrophy) are examples of disorders that may be confirmed or ruled out by diagnostic genetic testing and other methods (the sweat test for cystic fibrosis, see below, or a neurologic evaluation for myotonic dystrophy).
One issue involved in symptomatic genetic testing is the appropriate frequency of testing in view of rapidly expanding genetic knowledge and identification of genes linked to disease. Physicians frequently see symptomatic patients for whom there is neither a definitive diagnosis nor a genetic test. The as yet unanswered question is: should such persons be recalled for genetic testing each time a new test becomes available? Although clinics that perform genetic testing counsel patients to maintain regular contact so they may learn about the availability of new tests, there is no uniform guideline or recommendation about the frequency of testing.
Testing Children for Adult-Onset Disorders
In 2000 the American Academy of Pediatrics Committee on Genetics recommended genetic testing for persons under age eighteen only when testing offers immediate medical benefits or when there is a benefit to another family member and there is no anticipated harm to the person being tested. The committee considered genetic counseling before and after testing as essential components of the process (Muin J. Khoury et al, "Population Screening in the Age of Genomic Medicine," 2003, http://www.cdc.gov/genomics/population/publications/population.htm).
The American Academy of Pediatrics Committee on Bioethics and Newborn Screening Task Force recommended that genetic tests included in the newborn-screening battery should be based on scientific evidence. The academy also advocated informed consent for newborn screening. (To date, the majority of states do not require informed consent.) The Committee on Bioethics did not endorse carrier screening in persons less than eighteen years of age, except in the case of a pregnant teenager. It also recommended against predictive testing for adult-onset disorders in persons under eighteen years.
The American College of Medical Genetics, the American Society of Human Genetics, and the World Health Organization have also weighed in about genetic testing of asymptomatic children, asserting that decision making should emphasize the child's well-being. One issue involves the value of testing of asymptomatic children for genetic mutations associated with adult-onset conditions such as Huntington's disease. Because no treatment can be begun until the onset of the disease, and presently there is no treatment to alter the course of the disease, it may be ill advised to test for it. Another concern is testing for carrier status of autosomal-recessive or X-linked conditions such as cystic fibrosis or Duchenne muscular dystrophy. Experts caution that children might confuse carrier-status with actually having the condition, which in turn might provoke needless anxiety.
There are, however, circumstances in which genetic testing of children may be appropriate and useful. Examples are children with symptoms of suspected hereditary disorders or those at risk for cancers in which inheritance plays a primary role. In "Genetic Testing and Screening" (American Journal of Nursing, vol. 102, no. 7, July 2002), Dale Halsey Lea and Janet Williams cite children with a family history of familial adenomatous polyposis (FAP) and those diagnosed with certain childhood cancers, such as multiple endocrine neoplasia, as appropriate candidates for genetic testing. They observe that testing can assist to determine planning, surveillance, and treatment for those who are found to have the FAP genetic mutation. Genetic testing for certain childhood cancers may serve to predict risk and improve detection of subsequent malignancies. Lea and Williams concur that the child must agree to and understand the function of genetic testing, and they reiterate that to administer genetic testing to a child not only requires parental consent but also the child's consent.
New Testing Guidelines for Infants Sparks Debate
In the article "Panel to Advise Testing Babies for 29 Diseases" in the February 21, 2005, issue of The New York Times (http://www.nytimes.com/2005/02/21/health/21baby.html?pagewanted=1&ei=5090&en=5ea4e9b22ce822c8&ex=1266728400&partner=rssuserland), Gina Kolata reports that a federal advisory group recommendation advocating screening infants for twenty-nine rare medical conditions has generated debate among health care professionals and the general population. The advisory group not only seeks to expand newborn screening but also to standardize it from state to state. In 2005 some states screened for just four conditions while others test newborns for as many as thirty-five diseases.
Advocates of expanded newborn screening assert that while the twenty-nine conditions occur infrequently, there are effective, potentially lifesaving medical treatments for each condition. Opponents claim that the efficacy of treatment has not been adequately evaluated or substantiated. They further caution that screening detects even those infants with the mildest forms of the disorders and essentially forces parents and health care professionals to consider treatment that may be more harmful than the mild disorder. They also wonder about the advisability of labeling infants with diagnoses of diseases from which they may never suffer.