SCIENCE AND PROFESSION

Genetic counseling is a process of communicating to a couple the medical problems associated with the occurrence of an inherited disorder or birth defect in a family. Included in this process is a discussion of the prognosis and treatment of the problem. Specific reproductive options include abortion of an ongoing pregnancy, birth control or sterilization to prevent additional pregnancies, artificial insemination, the use of surrogate mothers, embryo transplantation, and adoption.

In all cases, the role of the counselor is to provide unbiased information and options to the couple seeking advice. The counselor must not only discuss the medical implications of a condition but also help to alleviate the emotional impact of positive diagnoses and, in particular, to assuage the guilt or denial that a diagnosis may elicit in parents.

The two major categories of medical problems covered by counselors are birth defects and genetic diseases. The first group includes Down syndrome and spina bifida, while the latter includes hemophilia, sickle cell disease, and Tay-Sachs disease. Although the distinction between these two categories can sometimes blur, the key difference involves the clear pattern of inheritance shown by the genetic diseases.

Humans have between thirty thousand and thirty-five thousand genes. Genes are segments of deoxyribonucleic acid (DNA) that are arranged in linear fashion along the forty-six chromosomes. Most genes contain the information necessary for the cells to produce a specific protein, which often is involved in controlling some critical physiological function. For example, the beta globin gene produces a protein called beta globin that makes up half of the hemoglobin that carries oxygen in the red blood cells.

A genetic disease can occur when the DNA changes in structure. Such a change is also known as a mutation. A mutation can lead to the production of a defective protein that cannot carry out its normal function, thus causing a physiological defect. In the case of beta globin, changing only one of the 106 molecules that make up this protein leads to a form of hemoglobin that can produce nonfunctional protein aggregates in red blood cells. These aggregates can cause the red blood cells to collapse and take on a sickle shape. Such cells lose their function, and the tissues are starved for oxygen-a condition known as anemia. This defect, which is called sickle cell disease, is a fatal, heritable disease. As with all genetic disease, such mutations are relatively rare. Certain diseases may, however, be more prevalent within certain ethnic groups; for example, African Americans have a high incidence of sickle cell disease, and Ashkenazic Jews have a high incidence of Tay-Sachs disease.

Humans have two of each kind of chromosome; one set of twenty-three is inherited from the mother, and the other set of twenty-three is inherited from the father. Thus, each person has two copies of each gene, one located on a maternal chromosome, the other on a paternal one. Many types of defects, such as sickle cell disease, require that both genes have mutations in order for the disease to have an effect. Individuals who have one normal gene and one with a mutation are normal but carry the disease; they can pass the mutation on to the next generation in their eggs and sperm. This type of disease is called a recessive genetic disease. The only way a child can have sickle cell disease is if both parents are carriers, since it is unlikely that a person affected by the disease will live long enough to have children.

Since it is equally likely for each parent to pass on the normal gene in eggs or sperm as to pass on the mutation, the laws of probability predict that, on the average, one-fourth of such a couple’s offspring should have the disease. One of the major tasks of a genetic counselor is to advise couples of these probabilities if the diagnoses and family histories suggest that they are carriers. Since the laws of genetics involve random occurrences, however, it is possible that in a family with three or four children, all the children will be normal, or that in another family, all the children will have the disease. This degree of uncertainty produces stress and anxiety in couples who seek counseling only to hear that they indeed are at risk. Discussing concepts that involve sophisticated genetic or biochemical themes or issues of probable risk with couples untrained in scientific thinking is difficult, especially considering the highly emotional atmosphere of such discussions.

Other diseases, such as Huntington’s chorea, also known as Woody Guthrie’s disease for the folksinger who was afflicted by it, are caused by a dominant mutation. A mutation is dominant when an individual needs to inherit only one copy of the mutation in order to have the disease. Unlike recessive diseases that can disappear from a family for generations, a dominant mutation can be inherited only from a person who has the disease. In most cases, such a person has one normal gene and one with the mutation, which means that there is a 50 percent chance that the gene will be passed on. Huntington’s chorea is a particularly insidious genetic disease, because the symptoms usually begin to show only in middle age, often after childbearing decisions have been made. Thus, the children of an afflicted parent may have had children before knowing whether they have inherited the mutation from their parents.

There are no cures for the permanent physiological defects that result from genetic disease. In some cases, the disease symptoms can be controlled by supplementing the protein that is lacking. Some forms of insulin-dependent diabetes and most cases of hemophilia can be treated in this way. In other cases, as with the disease phenylketonuria (PKU), special diets can prevent the severe neurological problems that inevitably lead to childhood death if the disease is left untreated.

DNA technology and genetic engineering offer potential cures for some diseases in which the primary defect caused by the mutation is well understood. Gene therapy is a process by which an additional copy of a normal gene is inserted into the cells of an affected individual or the defective gene is replaced by a normal one. Successful experiments with animals have given scientists confidence that these techniques will provide cures for many genetic diseases. These same DNA technologies are making better diagnoses possible and, as in the case of cystic fibrosis, are helping to extend the lives and enhance the quality of life of individuals afflicted with incurable diseases.

One of the more controversial aspects of genetic counseling is the procedure of screening. In this procedure, individuals suspected to be at risk are tested for the presence of a mutation. Screening can let people know whether they have a disease as well as whether they are carriers of the disease and therefore can pass the disease on to their children. Screening can be extended to all individuals, regardless of family or ethnic history. For example, in the United States, most states require that all newborn infants undergo a PKU test. This simple test involves taking a small sample of blood by pricking the heel of the baby. Although the costs of this screening are not insignificant, the benefit is that those infants found to have the disease can be treated immediately by being placed on a special diet so as to avoid the debilitating effects of the disease.

Other screening procedures are targeted at specific groups. The screening program for Tay-Sachs disease focuses on ethnic Jewish populations. This successful, voluntary program has reduced the incidence of Tay-Sachs disease significantly in the United States. The key to the success of the program was the money spent to educate the targeted group. In addition, key members of the population played a leading role in designing the overall program. Because of the much larger size of the potential group at risk, similar efforts to screen African American populations for sickle cell disease have been much less successful. Ethical concerns about the motivations behind government-sponsored or government-encouraged screening of minority populations make these programs difficult to implement. In addition, in mandatory programs, concerns about confidentiality and information release become major obstacles.

DIAGNOSTIC AND TREATMENT TECHNIQUES

Genetic counseling usually begins when a couple or an individual seeks the advice of a family physician or obstetrician regarding the medical risks associated with having a child. Motivating this request may be a previous birth of a child with a defect, a general uneasiness on the part of a couple worried about environmental exposure to potentially harmful agents, a family history of genetic disease, or advanced maternal age (which can be a factor in certain chromosomal abnormalities). Often, the family is referred to a genetic counseling clinic where most of the actual diagnosis and counseling will occur.

Arriving at a proper diagnosis for any obvious condition, as well as giving advice about potential risks, involves obtaining as much family history as possible with respect to the trait, as well as diagnostic information from the couple. If pregnant already, the woman may undergo a prenatal diagnostic procedure that could include ultrasound, blood tests, amniocentesis, and chorionic villus sampling.

Ultrasound is a technique that uses sound waves to visualize the exterior of the developing fetus. This widely used procedure is almost routine in many large urban hospitals. Ultrasound can be used to detect the presence of twins as well as of some profound birth defects such as hydrocephalus (water on the brain) or spina bifida. The latter defect, which involves the failure of the neural tube to close properly during development, leads to weakness, paralysis, and lack of function in lower body areas. The severity of the defect is hard to predict, and, unlike genetic disease, the incidence of recurrence is no higher than normal for subsequent children.

Supplementing ultrasound in the detection of spina bifida is a simple blood test that looks for a protein that the fetus spills into the amniotic fluid in higher quantities if the neural tube fails to close properly. The protein, which is called alpha-fetoprotein, crosses the placenta to circulate in the mother’s blood. The amount of this normal protein in the mother’s blood correlates with the developmental age of the fetus; therefore, an abnormal level might indicate a problem. Older-than-calculated fetuses and twins can both cause increased levels of alpha-fetoprotein, so care must be taken in this diagnosis. If abnormally high levels of the protein are found, amniocentesis would then be used to measure the protein level in the amniotic fluid, thus increasing the reliability of the diagnosis. In amniocentesis, a few teaspoonfuls of amniotic fluid are removed from the sac that surrounds and protects the developing fetus. Ultrasound is used to visualize the exterior of the fetus to allow the safe removal of this fluid, which contains some fetal cells. Biochemical tests can be performed directly on the fluid and results obtained quickly. Tay-Sachs disease is an example of a genetic disease that can be detected in this fashion, since fetuses with the disease fail to make an enzyme that their normal counterparts do make.

Many techniques, however, require obtaining large numbers of fetal cells and/or DNA. In these cases, the cells must be cultured for one to two weeks in a laboratory in order to get enough material to test. The delay between taking the sample and discussing the results with the clients is a source of stress and anxiety for parents undergoing counseling.

Preparing a karyotype, a photograph showing the numbers and sizes of the chromosomes of the fetus, is a commonly performed procedure following amniocentesis. Normal fetuses contain forty-six chromosomes, and any change in chromosome number, shape, or size can be detected by a skilled clinician. A large percentage of miscarriages involve fetuses with chromosomal abnormalities, so this diagnosis can be critical. A relatively common type of birth defect that can be diagnosed with a karyotype is Down syndrome. Most children born with Down syndrome have forty-seven chromosomes instead of forty-six; thus, this diagnosis is very accurate. In addition, the sex of the fetus can be determined from a karyotype, since male fetuses have an X and a Y chromosome while females have two X chromosomes. This information can be valuable to couples who are at risk for carrying a sex-linked genetic disease such as hemophilia, which could not affect any female offspring. Such information could potentially be used inappropriately for sexual selection of offspring, however, and the counselor must provide this information cautiously.

Amniocentesis is usually performed in the sixteenth week of pregnancy to allow the fetus to grow to a size at which the removal of a small amount of amniotic fluid would not be harmful. Although there is little risk to mother or fetus in this procedure, the delay associated with laboratory culturing means that results are often known in the eighteenth week of pregnancy or even later. At this stage, abortion becomes a more traumatic medical procedure. Chorionic villus sampling, on the other hand, can actually sample small amounts of fetal tissue directly. Since the procedure can safely obtain enough tissue to diagnose most problems and can be performed as early as the ninth or tenth week of pregnancy, abortion becomes a medically less traumatic option.

DNA technology provides the counselor with a battery of new diagnostic procedures that can look directly for the presence of a mutation in the DNA of the fetus. These tests can be performed on parents who are worried about being carriers for a particular disease or can be used on DNA obtained from fetal cells grown in a laboratory. Such tests have very high reliability and can give information about diseases such as sickle cell disease, Huntington’s chorea, muscular dystrophy, and cystic fibrosis.

The counselor’s task is to take the diagnostic results and interpret them in the context of the medical history and particular family situation. The counselor must point out the options available, both for further diagnosis to confirm or rebut less sensitive preliminary tests and to discuss potential medical interventions such as the special diets available for children born with PKU. In cases in which no medical intervention is possible, the severity of the problem should be discussed honestly so that the parents can choose either to continue or to abort the pregnancy. Other options, including adoption, artificial insemination, and embryo transplants, can also be evaluated. Finally, the risk of recurrence of the problem in future pregnancies should be discussed.

Counselors need to realize that their clients are often in emotionally fragile states. They must guard against using bias or interjecting their own personal beliefs or values when counseling their clients. Full disclosure of information, both verbally and in a carefully written report, is usually provided.

Compounding the tasks of the counselor is the fact that, in many cases, exact diagnoses are not yet possible. Sometimes, only the relative risks associated with another pregnancy can be determined. Different couples will perceive risks very differently depending on their own religious and moral backgrounds, as well as on the expected severity of the defect. In the case of a genetic disease such as Tay-Sachs, which is 100 percent fatal and requires extensive hospitalization of the child, a modest risk may be considered unacceptable, while in the case of a birth defect such as Down syndrome, whose severity cannot be predicted, and in which case the child may lead a long and rich life, a modest risk may be considered quite differently.

PERSPECTIVE AND PROSPECTS

The need for centers specializing in genetic counseling arose when it became clear that certain diseases and birth defects had a hereditary component. Many families request the services of counselors from these centers, and the centers are also involved in both voluntary and mandatory screening programs.

Physicians have always served as counselors to families, but the rapid advances made in genetics and molecular science during the second half of the twentieth century have clearly surpassed the abilities of most physicians to keep current with treatments and diagnoses. The first formal clinic for genetic counseling was established at the University of Michigan in the 1940s. Most clinics specializing in this field were based at large medical centers; first in major metropolitan areas, and later in smaller population centers.

Genetic counseling clinics usually employ a range of specialists, including clinicians, geneticists, laboratory personnel for performing diagnostic testing, and public health and social workers. In 1969, Sarah Lawrence College instituted a master’s-level program in genetic counseling to train candidates formally in the scientific, medical, and counseling skills required for this profession. Since that time, many other programs have been established in the United States. Most large counseling programs at medical centers use these specially trained personnel. In rural areas, however, family physicians are still a primary source of counseling; thus, genetic training is an important component of basic medical education.

The sophisticated medical diagnostic tools described above allow a counselor to provide abundant information to couples requesting counseling, but the power of DNA technology has expanded and will continue to expand the scope of current practice. Soon, counselors will not have to give advice in terms of probabilities and likelihoods of risk; molecular detection techniques will make possible the absolute identification of not only individuals with a disease but also related carriers.

As these DNA tools become more widely available, counseling will become a more integral part of preventive medicine. A DNA diagnostic procedure for a heritable form of breast cancer is available that allows women who have the mutation to monitor their health closely in order to receive prompt, lifesaving medical intervention. An important ethical issue here is that some women who have been diagnosed as having the mutation are undergoing preventive mastectomies without having developed any growths in order to ensure that they will not develop cancer. This radical therapy carries with it considerable emotional stress and should be undertaken only after consultation with a physician. As DNA-based diagnostic procedures, perhaps coupled with mandatory screening, become more commonplace, concerns about the release of this information to potential employers or health insurers will become more critical.

See also Abortion; Amniocentesis; Birth defects; Blood testing; Chorionic villus sampling; Diagnosis; DNA and RNA; Down syndrome; Ethics; Gene therapy; Genetic diseases; Genetic engineering; Genetics and inheritance; Hemophilia; Laboratory tests; Mutation; Niemann-Pick disease; Phenylketonuria (PKU); Screening; Sickle cell disease; Spina bifida; Tay-Sachs disease; Ultrasonography.