Genetic Counseling

No field of medical knowledge is exploding more rapidly and with more potential impact upon women -- and the reproductive choices they make -- than the field of genetics. Once almost an afterthought in the training of physicians, genetics and its relationship to human health and disease now makes front-page news with regularity. The news is both exhilarating and daunting.

Scientists are rapidly learning which of the estimated 100,000 genes located on chromosomes in each of our body's cells could be the cause of any of nearly 5,000 inherited disorders. With this new knowledge, genetic tests are being developed to look for specific disease genes, a step that could ultimately lead to better treatments and eventual cure of the conditions altogether. Moreover, prenatal tests of fetal health before birth can now predict earlier and with even greater accuracy whether there is a likelihood of an inherited disorder or birth defect.

Nevertheless, it is not always easy to decide when to use this technology, how to interpret the results, and what course of action to take. Families dealing with the possibility of an inherited disorder or birth defect in an unborn baby, or confronting the reality of a child or adult who is already affected, need the help of trained individuals -- medical geneticists and genetic counselors -- to establish a diagnosis and to guide them through the process of understanding the facts about the disorder, appreciating the potential risks to other family members, choosing a course of action, and coming to terms with their decision. This process is called genetic counseling. Although this chapter is presented as a guide for those contemplating using genetic services, it is far from encyclopedic; the field of genetics is moving too rapidly for that. Those seeking more detailed information about genetic testing should make contact with a medical geneticist or hospital genetics unit, or contact one of the agencies listed at the end of this chapter.

The Genetic Consultation

Testing and counseling go hand in hand in a genetic consultation. Counseling is needed to help the geneticist and the client decide mutually whether testing is appropriate and which tests may be needed; information from test results, including a possible diagnosis, is essential for counseling to be effective. From the start, the emphasis in genetic counseling is on educating you and the members of your family about the actual or suspected condition that has prompted the consultation so that you may become experts. If you or a member of your family is referred for a genetic consultation because of the existence or perception of some increased risk, a member of the genetic counseling team will discuss the reason for the referral with you and ask you some basic questions, including your date of birth, length of gestation if you are pregnant, information about any prenatal exposures (such as medications, smoking, alcohol or drug use, or chemicals at work), ethnicity, and details about your and your family's medical history. One result of this consultation is a diagram called a pedigree.

Sometimes, as part of this initial visit, you or your family member may be offered a physical examination by a medical geneticist, a physician trained in the specialty of genetics. During the examination, the medical geneticist can often observe certain physical characteristics that may speed the process of making the diagnosis or lead to the recommendation of appropriate tests. The benefits and risks as well as the limitations of each test will be explained so that you can arrive at a decision about whether or not to undergo the test. The counselor may give you brochures or offer to show you a videotape explaining the procedure. If you decide in favor of the test, you will be asked to sign an informed consent form, depending on the nature of the test. (Later in this chapter, we describe some tests that may be recommended.)

The results of the various tests will require study and interpretation. The next phase of the genetic counseling process is to put this information into perspective as a prelude to independent decision-making on your part. A member of the genetics team will discuss the cause of the condition, its variability, any available treatments, the likelihood that it may affect other family members, and its potential impact on family planning. The concept of risk is usually presented in terms of numerical probability (fractions or percentages), with the understanding that what seems a high risk to one person may not seem so to another.

Finally, the counselor will present the options, reproductive and otherwise, open to you and your family in a manner that does not favor one option over another. This non-directive approach respects the fact that decisions involving genetics are often difficult to make, take time, and must be made independently by the family in the context of their moral and cultural values, religious principles, reproductive goals, and perceptions of risk. Often, the social concerns of parents -- the cost of caring for a child with a birth defect or genetic condition, the presence or absence of family support, the availability of appropriate schooling, and access to support groups to alleviate stress -- weigh heavily in the decision-making process. The most productive genetic counseling sessions allow enough time for these concerns to be addressed.

When Genetic Counseling Helps

Genetic counseling can be helpful to any woman, either before or during pregnancy, who is concerned about the risk to her unborn baby posed by a number of situations. These may include:

  • a family history of genetic disease or birth defects,
  • a chromosome problem associated with advanced maternal age such as Down syndrome,
  • exposures to potentially harmful substances,
  • two or more unexplained miscarriages or a previous baby with a birth defect,

Likewise, families searching for explanations of the appearance of a genetic condition or birth defect in a family member can seek genetic counseling and testing to predict the likelihood that other family members will be affected. Far more than just testing, the genetic counseling process offers education about human inheritance and knowledge about specific disorders of concern to a family.


The Importance of Family History

Knowing the details of your family's medical history is an important component of the genetic counseling process.

Traditionally, women in the family are often the keepers of this information. The records and documents they accumulate may provide the first clues that an inherited condition in one or more family members could affect a prospective pregnancy, an unborn baby, or a living relative. Not all inherited disorders can be detected by testing, but many can. The test results can provide the basis for decisions about whether to continue a pregnancy, how to prepare for the birth of an infant with special needs, or how to anticipate or ameliorate an adult-onset genetic disease. Even if a family member is adopted, it may be possible to find out medical information about the birth family, depending on state laws governing the release of such information.

Constructing a diagram of your family's health history, called a pedigree or family tree, is not difficult, but you must follow certain basic rules:

  • Begin the pedigree with yourself and work backwards to include at least three generations if possible.
  • Squares represent males and circles represent females.
  • Parents are connected to each other with horizontal lines and to their children, left to right in birth order, with vertical lines.
  • Smaller symbols indicate stillbirths and miscarriages.
  • Generations are numbered using Roman numerals.

The diagram below shows a pedigree of a family with several members who have Huntington's disease. (See Fig. 14.1). (Although it is generally the task of the genetics professional to prepare a formal pedigree such as this one, it is useful to put together a rough diagram yourself containing the important facts before speaking with a geneticist or genetic counselor.) A pedigree takes into account not only any genetic or familial disorders that run in the family, but also the ethnic and geographic origins of family members. This information is important, as we shall see later, in the inheritance of such conditions as sickle cell disease (mostly in African-Americans, Caribbeans, and Latinos), Tay- Sachs disease (mostly in Jews of Eastern European ancestry), and thalassemia (mostly in those from Mediterranean countries and much of Asia). It is also important to know about any consanguineous marriages (marriages between relatives) and about any spontaneous abortions, stillbirths, neonatal deaths, chromosome abnormalities such as Down syndrome, birth defects such as cleft palate and congenital heart defects, or mental retardation. In the case of birth defects or mental retardation, it is helpful to have photographs of the affected family member(s) as well as any available medical records. When possible, a physical examination of the relative is very important. Any of this information may supply the clues needed to learn about an actual or potential inherited disorder or birth defect.

While a family history of an inherited disorder or birth defect is certainly not the only reason for seeking genetic counseling, the pedigree often forms the foundation upon which the counseling process can build.


Genetic Counseling and Pregnancy

Most women seek or are referred for genetic counseling because they are pregnant or intend to become pregnant and have some questions or concerns about the health of their unborn baby. These concerns can be broken down further into two categories: family history indicators (such as ethnic predispositions to inherited disorders, or a history of known genetic disorders, birth defects, or chromosomal abnormalities) and other indicators (such as advanced maternal age, abnormal test results in pregnancy, or exposure to potentially harmful substances during pregnancy).

Family History Indicators

Ethnic Predisposition

Ethnic predisposition to a particular genetic disorder is an important reason for obtaining genetic testing and counseling during pregnancy, if not before. The following conditions are all autosomal recessive, which means they require two genes -- one from each healthy parent -- for the condition to occur in a child.

  • Sickle Cell Disease. In sickle cell disease, the normally flexible and round red blood cells become rigid and crescent-shaped. The disease causes anemia, bouts of pain caused by blocked blood vessels, and increased susceptibility to serious infections such as pneumonia. About 1 in 10 African-Americans carries one recessive gene for sickle cell disease; this is called sickle cell trait. More than 50,000 Americans have two copies of the gene and have sickle cell disease. People of Caribbean origin and many Latinos also have sickle cell trait, as do smaller numbers of Greeks, Italians, Asian Indians, and Saudi Arabians. When both partners have sickle cell trait, they have a one in four chance with each pregnancy of having a child with the disease. This can be determined during pregnancy by prenatal diagnosis or at birth by newborn screening.
     
  • Thalassemia. Individuals of Asian and Mediterranean origin (including Greeks and Italians) are at risk of inheriting thalassemia when both parents carry a single recessive gene (called thalassemia trait). Some forms of thalassemia are very serious and may result in stillbirth or cause severe anemia, requiring a continuous program of blood transfusions for the child or even bone marrow transplantation. Prenatal diagnosis is also available for thalassemia.
     
  • Tay-Sachs and Gaucher Disease. Couples of Eastern European (Ashkenazi) Jewish descent need to be aware that they might be carriers of the recessive genes for a number of disorders, of which Tay-Sachs disease is the best known. Babies with Tay-Sachs disease are born deficient in an enzyme, hexosaminidase A, that is essential for proper nerve cell functioning. These children gradually lose mental and physical functioning and gradually die before the age of five. Approximately 1 in 25 -30 Ashkenazi Jews is a Tay-Sachs carrier; the rate for Sephardic Jews (those originally from Spain, Portugal, and North Africa) is about 1 in 100. Screening with a simple blood test before or during pregnancy is a routine practice, and prenatal testing is also available.

    Another recessive genetic disease caused by an enzyme deficiency, Gaucher disease, is even more common than Tay-Sachs disease, with a gene carrier rate of approximately
    1 in 12 Ashkenazi Jews. Gaucher disease causes the build-up of fatty deposits in the liver and spleen, resulting in the enlargement of these organs. It can vary from mild to severe. Carrier testing and prenatal diagnosis are available to those with a family history of the disease. Routine testing is not currently offered.
     
  • Cystic fibrosis. Caucasians are at increased risk for cystic fibrosis (CF), a generally severe disease characterized by thick mucus secretions in the lungs and other parts of the body. There are approximately 30,000 Americans with CF and as many as 1 Caucasian American in 20 may carry one of the many forms of the gene for CF. CF is less frequent in Latinos, infrequent in African-Americans, and very rare among Asians. When both members of a couple carry such a gene, they have a one-in-four chance with each pregnancy of having a child with CF. At present, a DNA-based test for the cystic fibrosis gene is available especially to people with a family history of the disease (see below), but the test is not yet able to identify all carriers in all ethnic groups. In most cases, a fetus at risk for CF because of family history can be identified through prenatal diagnosis. In the future, testing for the CF gene may be available for population screening.

The diseases mentioned above are only a few of the numerous genetic conditions for which specific ethnic groups are at special risk. Less often, these conditions may also affect members of other ethnic or racial groups. However, the frequency of the gene in the particular group combined with the severity of the disease may suggest the need for targeted screening to identify asymptomatic carriers of the specific gene, a process called genetic screening. In any case, it is prudent to remind the obstetrician and the genetic counselor of your and your partner's ethnic background so that you can be offered the appropriate testing.

Known Inherited Disorders

Many people are aware that one or more members of their family has a condition that seems to be inherited. Naturally, they may be concerned that a future child of theirs will develop the same condition. Some examples of these inherited diseases are cystic fibrosis; neurofibromatosis, a condition causing a wide range of symptoms including darkened patches of skin ("cafe au lait" spots) and multiple benign tumors of nerve and fibrous tissue; hemophilia, a disorder of the clotting mechanism in the blood; the fragile-X syndrome, the most common inherited form of mental retardation in males; and muscular dystrophy, a group of muscle-wasting diseases. Each of these diseases is inherited in a different pattern, and each has different recurrence risks: cystic fibrosis is an autosomal recessive disorder, neurofibromatosis is an autosomal dominant disorder, hemophilia is X-linked recessive (transmitted on the X chromosome), and the fragile-X syndrome is inherited in a manner that does not fit neatly into any of these categories. There are many varieties of muscular dystrophy, each inherited in a specific pattern (see Chapter 13).

What many of these and other inherited disorders have in common, however, is the increasing availability of tests predicting whether an individual or a fetus carries the gene for the condition. Couples aware of a family history of these or other inherited diseases can now seek genetic counseling, either to test for the presence of the altered gene or genetic marker in their blood or to undergo prenatal testing for the disorder. The information they obtain through testing and counseling helps the couple decide about the pregnancy and about care of the infant after birth. For example, in the case of cystic fibrosis (CF), the gene causing the disease has been traced to the long arm of chromosome 7, and specific carrier tests using DNA analysis can now identify the majority of mutations of this gene. In fact, about 90 percent of Caucasian-American CF carriers can now be identified by DNA testing for 32 mutations, a process called mutation analysis or direct gene detection. (Carrier identification is more direct if the particular mutations in the family member with CF are identified. Unfortunately, failure to detect a mutation does not ensure that a person is not a carrier, since approximately 10 percent of Caucasian-American carriers will not be detected by current methods. The percentage varies depending on the ethnic group.)

Since those affected by CF can now live well into their twenties and even longer, a woman with CF may seek genetic counseling to ascertain the risk that a child of hers will have the disease. If testing of her partner by mutation analysis is negative, the chance for CF in a child of theirs is much reduced but not eliminated. If her partner does have a CF mutation, prenatal diagnosis can determine whether the baby will be affected.

Birth Defects

There are many types of birth defects, all with their own causes. A family history of problems such as neural tube defect, congenital hip dislocation, cleft lip, and cleft palate is a good reason to seek out the help of a geneticist when you are pregnant or planning a pregnancy. Let's choose one of the more common birth defects, congenital heart defects (CHD), to illustrate.

There are numerous types of CHD that affect the various structures of the heart with varying degrees of severity. The prevalence of these defects in liveborn infants is about 4 -8 for every 1,000 births. Sometimes congenital heart defects are associated with particular physical features, called extracardiac malformations, that make specific inherited disorders or chromosomal problems easy to identify. Many of these defects once caused death in infancy. Today, because of medical and surgical intervention, increasing numbers of individuals with CHD are surviving to adulthood, thus increasing the need for genetic counseling of the families of affected individuals.

Most congenital heart defects are probably the result of combined genetic and environmental factors (multifactorial inheritance). Virtually all forms of CHD show some familial pattern of occurrence: Recent studies have demonstrated rates of familial occurrence for obstructive defects involving the left side of the heart that are four to six times higher than for other types of defects. For example, in siblings there is about a 14 percent rate for hypoplastic left heart syndrome, an 11 percent rate for bicuspid aortic valve, and an 8 percent rate for coarctation of the aorta. The risk to children when one parent has CHD is generally between 2 and 4 percent. Higher rates have been reported in some forms of CHD if the parent with CHD is the mother.

Genetic counseling can be of enormous help to the family concerned about the recurrence of a congenital heart defect. The interpretation of recurrence risks varies depending on the specific anatomic defect or genetic syndrome and the presence of other affected relatives. A complete family history taken during genetic counseling can also reveal any exposures to harmful substances that may have contributed to the defect in question. Prenatal diagnosis, specifically fetal echocardiography (sonography of the fetal heart), is available at many centers beginning at about the twentieth week of pregnancy, sometimes in conjunction with amniocentesis and chromosome analysis. If tests reveal the presence of a congenital heart defect, the genetics professional and a pediatric cardiologist can prepare the parents for the extent of the disability so that they may make a decision about the pregnancy and/or prepare in advance for the delivery and early nursery care.

Mental Retardation

Mental retardation in a family is another important reason for seeking genetic counseling. The condition has many genetic as well as nongenetic causes. Using one example, fragile-X syndrome is the most common inherited form of mental retardation in males. Only recently described, fragile-X syndrome is caused by an abnormally expanded gene associated with a so-called fragile site on the X chromosome transmitted by one of the parents. The presence of fragile-X syndrome in a family is often suspected when there are one or more retarded members, usually boys, who may have elongated faces, prominent ears, and unusually large testes after puberty. Girls with fragile-X are affected less often but may have learning disabilities or mild mental retardation. In affected boys, the expression of fragile-X syndrome is variable and mental retardation may be mild or severe. Because fragile-X carriers, both male and female, may not show any symptoms of mental retardation at all, carrier testing is recommended to help the family determine the risk to prospective children. In addition to chromosome analysis, direct DNA testing for the fragile-X gene is now available. Prenatal diagnosis can even predict to some extent the severity of the mental retardation.

Stillbirths, Unexplained Miscarriages, or Infants with Multiple Congenital Malformations

A personal or family history of stillbirths, multiple unexplained miscarriages, or chromosomal problems such as Down syndrome is another reason for pursuing genetic testing and counseling. Miscarriages, also called spontaneous abortions, are quite common and occur in about 15 percent of pregnancies. Chromosomal abnormalities in the fetus, usually extra or missing chromosomes, account for approximately half of all first-trimester miscarriages. (About 7 percent of stillbirths have a chromosome abnormality, and one of every 200 liveborn infants has a chromosome abnormality such as Down syndrome.) In searching for the cause of a miscarriage or stillbirth, the physician can order a chromosome analysis of the fetal cells; if the results are abnormal, this will provide an explanation for the loss of the pregnancy. In most cases of missing or extra chromosomes, no chromosome problem is found in the parents. However, when there is a liveborn infant with Down syndrome, there may be an increased risk for recurrence in future pregnancies.

Two or more miscarriages, an unexplained stillborn, or a liveborn with physical abnormalities may also be the result of a different kind of chromosome imbalance. One of the parents, for example, may have a chromosome "rearrangement." An example of such a rearrangement is a so-called balanced translocation, in which material normally found on one chromosome has been exchanged with material from another. This transfer causes no health problems for the parent who carries the rearrangement but may result in chromosomally abnormal egg or sperm cells (germ cells) that lead to a chromosomal imbalance in the fetus. A miscarriage, a stillbirth, or a liveborn with multiple congenital malformations may be the result.

In another type of rearrangement, a part of one chromosome can break and rejoin to itself in an inverted position, reversing the gene order on that chromosome. While not all inversions lead to problems, sometimes an inversion in the chromosomes of a parent can cause the formation of abnormal germ cells. Approximately 1 in 20 couples with multiple miscarriages has some kind of chromosome rearrangement in one parent. Knowing about such chromosome rearrangements can help to explain the loss of repeated pregnancies and assist the couple in doing some advance planning for the next pregnancy.

Other Indicators for Genetic Counseling in Pregnancy

Maternal Age

The most common reason today that women seek genetic testing and counseling during pregnancy is advanced maternal age. Most doctors currently consider advanced maternal age as 35 years or older at delivery because the chance that a baby will be born with Down syndrome rises markedly with increasing age (see Figure 2). Down syndrome, also called trisomy 21, is the most common chromosomal abnormality among liveborn infants and is due to an extra chromosome number 21 (trisomy 21), resulting in a total of 47 chromosomes instead of the usual 46. The reason for this is usually the failure of separation of the two paired chromosomes during germ cell formation, resulting in a sperm or more often egg cell with 24 instead of the usual 23 chromosomes. Children with Down syndrome have characteristic facial features, including skin folds at the inner eyelids and upslanting eyes. They have some degree of mental retardation and may have congenital heart defects. While these children can learn to read and write and participate in family life, adults with Down syndrome continue to need supportive services.

Other much rarer chromosomal abnormalities also become more prevalent as maternal age increases. These include trisomy 18 and trisomy 13, both of which result in severe physical and mental defects. Infants born with either of these syndromes rarely survive more than a few months.

Because the risk for these and certain other chromosomal abnormalities increases with maternal age, it is customary for physicians to offer prenatal testing for their pregnant patients who will be 35 or older at the time of delivery, regardless of the number of prior pregnancies they may have had. Prenatal diagnosis of Down syndrome and other chromosome problems is made using the techniques of amniocentesis, chorionic villus sampling (CVS), and chromosome analysis, all of which are covered later in this chapter.

Alpha-fetoprotein and Other Screening Tests

Alpha-fetoprotein (AFP) is a protein produced by the developing fetus that is excreted into the amniotic fluid in small amounts. Normal levels of amniotic fluid AFP vary with gestational age. Minute quantities also find their way into the maternal bloodstream. Excessive amounts, however, suggest the possibility of a neural tube defect, a structural problem in the formation of the brain and spinal cord. Neural tube defects can range from a failure of brain development (anencephaly) to a structural defect in the spinal cord and the bone, muscle, and skin that normally cover it (spina bifida or meningomyelocele). Because a fetus with an open spine defect will leak additional amounts of AFP into the amniotic fluid, AFP levels in the mother's bloodstream, called maternal serum AFP (MSAFP), will also be higher, suggesting that her fetus may have a neural tube defect. However, MSAFP may also be elevated for other reasons, such as the fetus having kidney disease, a defect of the abdominal wall (omphalocele or gastrochisis), the existence of a twin pregnancy, or incorrect gestational dating. Low levels of MSAFP have been associated with an increased risk of Down syndrome, making the test a useful screen for Down syndrome pregnancies in women under age 35. Other serum markers in maternal blood -- human chorionic gonadotropin (HCG) and perhaps estriol -- are also useful screening tools in combination with MSAFP for Down syndrome and most likely trisomy 18. Maternal serum screening using a combination of two or three serum markers is abnormal in most pregnancies with Down Syndrome.

Since virtually all obstetricians are now offering their pregnant patients maternal serum screening at about 16 weeks gestation, it is important to understand the test for what it is -- a screening test. Such a test may suggest an increased risk but does not prove conclusively the existence of some condition in the fetus. Many factors may influence levels of MSAFP, among them the age of the fetus, a twin pregnancy, race, the weight of the mother, and maternal insulin-dependent diabetes. If, after considering these factors, MSAFP levels are still abnormal, further testing by ultrasound and amniocentesis is recommended. Even then, results are usually normal, with a normal outcome of the pregnancy. Maternal serum screening tests for use in the first trimester are being developed.

Exposures during Pregnancy

Many pregnant women seek genetic counseling because they have been exposed -- or fear they may have been exposed -- to substances or situations that are potentially harmful to the fetus. Environmental agents that can cause birth defects in the fetus are called teratogens, and they include certain medications, maternal diseases, infections, X-ray exposures, alcohol, and drugs. Exposure to chemicals and other agents in the workplace is another potential cause of birth defects (see Chapter 6). As might be expected, there is a often a dose-response relationship between the degree and timing of exposure to a teratogen and the potential for birth defects, although for most teratogens the level of safe exposure is not known.

Most teratogens cause damage during the first trimester of pregnancy when the embryo is undergoing rapid development and cellular differentiation. However, even within the first trimester there is an especially critical window of opportunity -- usually between the eighteenth and the fortieth day after conception when most organ systems are developing -- where the potential for harm is greatest. However, organ systems such as the nervous system continue to develop throughout pregnancy and remain vulnerable to birth defects caused by teratogens. To complicate matters, maternal and fetal genetic differences make some fetuses more susceptible than others to teratogenic exposures during pregnancy. For some exposures, however, there are methods to estimate the level of risk to which the fetus has been exposed and to evaluate fetal health. The following exposures are a partial listing of those with the potential to cause harm during pregnancy.

Rubella: When maternal rubella (German measles) occurs during the first eight weeks of pregnancy, the chance for birth defects in the newborn is about 85 percent. However, the potential for harm still exists into the second trimester. The infection in the mother may be mild or even go unnoticed, but the effects on the fetus can be numerous and may include growth deficiency, hearing loss, eye problems such as cataracts or glaucoma, heart defects, and mental retardation. Fortunately, there is an effective vaccine against rubella infection routinely given to all children in the United States. For women who have not been vaccinated in childhood, there is a simple blood test available to determine their immunity to rubella. When rubella immunization is done before planning a pregnancy, the vaccine poses no danger to the fetus. Even if inadvertently given during pregnancy, it appears to pose minimal, if any, risk.

Cytomegalovirus: One in every 100 infants born in the United States has cytomegalovirus (CMV), a virus that causes a mild, flu-like illness in the mother or no symptoms at all. Severe problems to the fetus can result when the mother has the virus for the first time during her pregnancy (primary infection). Although the majority of these babies are asymptomatic at birth, the 10 percent of babies who do develop early symptoms have small heads (microcephaly), mental impairment, problems with the retina of the eye, hearing loss, jaundice, and enlargement of the liver and spleen. Mortality is relatively high among this group of infants, about 20 to 30 percent. However, even babies who are asymptomatic at birth may go on to develop problems such as microcephaly or a progressive hearing loss. In addition, there is evidence that women who have had CMV in the past (recurrent maternal infection) may also have babies at some risk for hearing impairment. Again, a simple blood test can tell you about your immunity to CMV.

Toxoplasmosis: Toxoplasmosis is caused by an intracellular parasite sometimes present in uncooked or poorly cooked meat and in cat feces. It can result in a mild, flu-like illness that causes swollen glands and fatigue or has no symptoms at all. If the infection occurs in the woman during pregnancy, transmission to the fetus is quite possible, potentially causing a wide range of problems, regardless of when the mother was infected during pregnancy. These problems include mental retardation, convulsions, inflammation of the choroid and retina of the eye, hydrocephaly or microcephaly, and hearing loss. Other problems in these infants are anemia and jaundice. While many babies with toxoplasmosis are asymptomatic at birth, they may go on to develop problems in infancy and childhood, such as deafness, impaired vision, and mental retardation. However, once a woman has developed immunity to toxoplasmosis, the chance for problems in future babies is very low. Blood tests to determine immunity to toxoplasmosis are available.

Chicken Pox: Varicella infection (chickenpox) in the mother causes few problems with fetal development in most instances. When it does cause problems (in less than 5 percent of cases and mainly during the first trimester of pregnancy), it can result in prematurity and growth deficiency, as well as a characteristic scarring of the skin overlying the affected sensory nerves. Mental retardation, seizures, malformation of the limbs, and eye problems may also occur. Again, the risk in the first trimester is greater than in the second trimester. A test for immunity to varicella infection is available and a new vaccine is currently under consideration for general use.

There are other important infections in the mother, such as herpes, hepatitis, HIV infection, and so on, that can be transmitted to the fetus during pregnancy.

Maternal Diabetes: Poorly controlled diabetes in the mother can result in a wide range of infant birth defects, including central nervous system defects, neural tube defects (anencephaly and meningomyelocele), congenital heart defects, vertebral malformations, and malformations of the skeletal, genitourinary, and gastrointestinal systems. The period of greatest risk to the fetus is the first eight weeks of pregnancy. Most of the defects appear to be related to elevated blood sugar in the mother, so optimal control of sugar metabolism in the mother, both before conception and throughout pregnancy, can reduce the likelihood of birth defects. Good control of sugar can also decrease the chance that a baby will be larger than normal at birth (macrosomia) or will develop low blood sugar or low calcium levels soon after birth. Prenatal monitoring and delivery of the baby in a well-equipped facility can minimize complications. (See Chapter 29 for more information on diabetes.)

Alcohol: The effects of alcohol on the fetus, called fetal alcohol syndrome (FAS), include a spectrum of problems, such as growth deficiency and developmental delay, characteristic facial features, and congenital heart defects. The most serious effects involve the nervous system and can result in mental retardation, poor motor development, and hyperactivity. In fact, FAS is now the leading cause of mental retardation in the United States. Because some effects on the fetus can occur in women consuming even moderate amounts of alcohol (at any time in pregnancy but especially during the first trimester), the best advice to pregnant women is to avoid alcohol altogether.

Cocaine: Cocaine is currently used by more women of childbearing age than any other drug. Its effects on the fetus can be wide-ranging and severe: spontaneous abortion and stillbirth, placental abruption (separation), prematurity, low birth weight, brain hemorrhage, neurological and behavioral abnormalities, and possibly gastrointestinal and genitourinary malformations. Cocaine causes constriction of blood vessels, and this suggests that disruption of optimal blood supply to the fetus may lead to many of the problems associated with its use. Because cocaine in all its forms can harm the fetus at any point during the pregnancy, its use should be strictly avoided.

Medications: About 5 to 10 percent of pregnant women taking Dilantin (phenytoin), one of the most commonly prescribed drugs to control epileptic seizures, give birth to an infant with a recognizable pattern of facial features, underdeveloped nails, congenital heart defects, and occasionally learning difficulties. Other babies exposed to Dilantin may show only very mild effects. Most show no effects at all. Tegretol (carbamazepine) and Depakene (valproic acid) are sometimes associated with malformations in the fetus, especially neural tube defects such as meningomyelocele (about 1 in 100). Women with seizures who are considering a pregnancy will benefit from consultation with their treating physician or a medical geneticist to consider both the type of medication and the dose for optimal control of seizures during pregnancy.

Accutane, an anti-acne medication, may cause numerous severe fetal problems, including neurological, heart, and facial defects. Lithium, prescribed for bipolar disorder (formerly called manic-depressive illness), can cause a specific type of congenital heart disease in infants exposed to it during the first trimester of pregnancy. Examples of other medications known to cause birth defects when taken during pregnancy include diethylstilbestrol or DES (structural changes in the cervix and vagina and, rarely, adenocarcinoma of the vagina), tetracycline taken in the second and third trimester (staining of the teeth), and Coumadin, an anticoagulant (multiple neurological and skeletal anomalies). If you are planning a pregnancy, be sure to ask your physician to check on any risks associated with both your old and newer medications.

Exposures of the Father

There is some preliminary evidence that exposure of the father to certain environmental agents may also cause damage to the sperm and possibly to the developing fetus. A recent study of cocaine-using fathers found evidence that the drug can bind to sperm and, if present at conception, may cause damage to the embryo. In addition, a father's social drinking may have an indirect effect on fetal health: it may make it more difficult for his partner to avoid drinking alcohol altogether during her pregnancy. In the future, there is likely to be a great deal more research in this important area.

Exposure to X-Rays and Other Imaging Techniques: Although very large doses of radiation have been associated with fetal loss and microcephaly, the lower doses of radiation delivered during diagnostic X-ray examination are believed to pose little danger to the fetus. Nevertheless, as a general rule, X-ray examinations should be performed before a pregnancy or delayed until after delivery, unless medically necessary. If you need to have X-rays performed on another part of your body during pregnancy, be sure to ask the radiologist to shield your pelvis and abdomen. You should also ask about the safety to the fetus of the radio- opaque dyes sometimes used during X-rays.

Nuclear scans use radioactive substances in small amounts to diagnose certain medical conditions. Some of these substances have the potential to cause harm to the fetus. If you are pregnant or planning to become pregnant, alert your physician.

Magnetic resonance imaging (MRI) does not use ionizing radiation to visualize structures in the body. While the safety of MRI in early pregnancy is still under investigation, it is wise to consult your doctor about the latest research developments.

Sonography is a commonly used imaging technique, employing sound waves, that is safe for the fetus. Investigation into the risk of maternal-fetal exposure to potential teratogens continues. For example, chronic use of megadoses of vitamin A, not generally thought of as harmful in the past, are now considered a potential cause of malformations in the fetus. Consultation with your doctor before pregnancy will help you to avoid potentially harmful exposures.

Genetic Deafness

More than half of all childhood deafness can be traced to genetic causes. Close to 200 types of genetic deafness exist, about a third of which occur with other physical symptoms, such as changes in the eyes, the ear shape, the heart, bones, kidneys, or other parts of the body. These combinations of symptoms are called genetic deafness syndromes. Not all types of genetic deafness are present from birth; it is possible for a child to be born hearing and for genetic deafness to manifest itself later in childhood or even in adulthood.

Genetic deafness must be differentiated from environmental deafness resulting from maternal infections such as rubella or cytomegalovirus (CMV), from certain diseases such as meningitis, or loud noises later in life. Environmental deafness has no effect on the genes of the person who is deaf, and such a person is likely to have children with normal hearing.

Genetic deafness can be inherited in a variety of ways. The most common mode of inheritance, accounting for 80 to 85 percent of all genetic deafness, is autosomal recessive, in which two genes are needed -- one from each hearing parent -- for deafness to occur. About 15 to 20 percent of genetic deafness is autosomal dominant, or caused by a single dominant gene. In this form, there is a 50 percent chance with each pregnancy that a child will inherit the gene for deafness from the deaf parent. X-linked deafness, in which the gene for deafness is carried on the X chromosome, is very rare, causing only about 1 to 2 percent of genetic deafness.

Genetic counseling can be very beneficial, both for hearing adults who have a deaf child or another family member who is deaf and for deaf adults themselves. In the case of hearing parents, the geneticist or genetic counselor may be able to identify the type of deafness in the family member, help the family to anticipate the likelihood that future children will be deaf or hearing, and recommend hearing tests soon after birth. Genetic counseling also may provide the first opportunity for a deaf individual to understand the cause of his or her deafness, and may answer questions about childbearing. When deafness is part of a syndrome including other physical problems, genetic services can offer help in coordinating access to other medical specialists. In recent years, the genetics community has become increasingly sensitive to the unique cultural, linguistic, and communication issues that are shared by deaf people.

Other Reasons for Genetic Counseling and Testing

Once again, family history is a major motivating factor for consultation with genetics professionals, even when a specific pregnancy is not the immediate concern. For example, a family might want to ascertain the risk, based on family history, that one or more of them might develop a genetic disease of adult onset, such as adult polycystic kidney disease, Huntington's disease, or a hereditary form of cancer. Another family may simply wish to gain an understanding of the origin of a condition, such as genetic deafness, that appears in some family members.

As with genetic counseling during pregnancy, the importance of gathering your family's health history cannot be overemphasized. The conditions discussed below represent only a few of those that may be of concern to families and individuals.

Some Adult-Onset Genetic Diseases: Adult Polycystic Kidney Disease, Familial Hypercholesterolemia, and Hereditary Cancers

The dilemma facing all those at risk for adult-onset genetic diseases is that symptoms may not appear until well into middle age or later, long after families have been completed and disease-causing genes passed on to children.

  • The prototype for this kind of condition is adult polycystic kidney disease (APKD), easily the most common genetic disease with approximately 500,000 Americans of all races and both sexes affected. Most often caused by an altered gene on chromosome 16, dominantly inherited APKD leads to the development of hundreds, perhaps thousands, of renal cysts that disrupt kidney function and may lead ultimately to renal failure and the need for a kidney transplant. The liver, spleen, and pancreas also may develop cysts, and in some families there may be an increased risk of cerebral aneurysm. Screening with sonography can reveal cysts in the kidney before symptoms appear. A DNA test is available to tell whether an individual has a high probability of carrying the gene and may develop the disease later in life. However, this test is only useful in families in which there are known cases of APKD and DNA of these individuals can also be studied. Not surprisingly, this kind of predictive testing imposes a burden of information on individuals that may cause considerable emotional discomfort. Recently the gene on chromosome 16 causing APKD was identified. This may soon allow for direct testing for the gene without the need to study family members.
     
  • Familial hypercholesterolemia (FH) is another common inherited adult-onset disease, causing high blood cholesterol levels and precipitating a heart attack as early as age 35. There are several types of FH, the most common of which is caused by a single dominant gene found in approximately 1 of every 500 Americans. FH effectively blocks the entry of cholesterol into the body's cells, trapping it in the bloodstream, where it accumulates and causes atherosclerotic plaques. A family history of early heart attacks certainly suggests the need for cholesterol screening. Although the first heart attack may not occur until the fourth decade or later, high blood cholesterol levels can be detected in childhood, alerting primary care physicians and geneticists to the possible presence of FH in the family. There are specific genetic tests that can confirm that diagnosis. Control of cholesterol levels can then be achieved, in most cases with a combination of dietary and lifestyle changes and medications.
     
  • Five to ten percent of all cancers are dominantly inherited, among them hereditary breast and ovarian cancers, familial adenomatous polyposis (a form of hereditary colon cancer), and hereditary nonpolyposis colon cancer. In each of these cancers, an accurate family history alone may be sufficient to identify individuals who are at risk for the disease and should be offered surveillance and/or genetic testing. In some cases, DNA testing can even identify gene carriers for specific cancers. At this early stage, some form of intervention can often reduce the risk or minimize disability.
     
  • A gene for hereditary breast cancer, transmitted in an autosomal dominant fashion, has just been identified on the long arm of chromosome 17. This will soon allow for direct testing of women at risk for alterations in the gene. Even now, DNA testing is useful in selected families. A second gene for hereditary breast cancer has been located on the long arm of chromosome 13. Early onset of breast cancer (in the thirties or even younger), the increased risk to the other breast, and the occurrence of early breast cancer in relatives help to differentiate hereditary breast cancer from nonhereditary forms. Women at risk for hereditary breast cancer -- constituting 5 to 9 percent of all breast cancers -- are currently offered earlier mammograms, more frequent breast examinations, and in selected cases preventive mastectomy.

    Similarly, family members at high risk for hereditary ovarian cancer can be identified by their position in the pedigree. In both these cancers, close female relatives, usually daughters, sisters, and mothers of the affected person, face a nearly
    50 percent risk over time of developing the cancer. In some families, predisposition to both ovarian and breast cancer appears to be governed by a single gene, found on the long arm of chromosome 17.
     
  • Familial adenomatous polyposis (FAP) is an autosomal dominant condition, traced to a gene on chromosome 5, in which dense carpets of precancerous polyps blanket the colon. In FAP, physicians can detect asymptomatic gene carriers by early adulthood by examining the retina of the eye for certain nonpathologic changes and the colon for polyps. Since colon cancer usually develops in these individuals in early to middle adulthood, screening with colonoscopy and surgical intervention are also offered early. Preventive proctocolectomy (removal of the colon and rectum) eliminates the risk to the individual who carries the gene for this trait. (A DNA test to identify gene carriers has recently been developed.)
     
  • Another autosomal dominant condition, hereditary nonpolyposis colon cancer, accounts for as much as 13 percent of all colon cancers. Gene carriers of this disorder are at increased risk for cancers of other parts of the body as well. Recent identification of several genes responsible should soon allow recognition of presymptomatic family members.

In the examples above, genetic testing and counseling, while often generating anxiety, can also provide relief from uncertainty and the hope for prevention or amelioration through new surveillance techniques and improved medical and surgical treatments. Unfortunately, there are other adult-onset diseases for which advances in knowledge on the contribution of hereditary factors have not yet resulted in specific genetic tests. Just a few examples of these are lupus, rheumatoid arthritis, alcoholism, schizophrenia, and most forms of diabetes and Alzheimer's disease.

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Genetic Tests and What They Indicate

Ultrasound Examination (Sonography)

A routine part of prenatal care for many women, sonography or ultrasound examination is a valuable tool for the estimation of gestational age, placental and fetal position, and twin pregnancies (level I or obstetric sonography). Sometimes other problems are discovered during a routine examination; because it shows some of the physical features of the fetus on a screen, ultrasound can detect certain structural birth defects. Fetal or level II sonography is performed if there is a suspicion that a structural birth defect may be present. For example, some neural tube defects such as anencephaly or meningomyelocele congenital heart and kidney malformations, and skeletal defects can be confirmed with this test.

An abdominal sonogram for fetal anatomy is performed in a doctor's office or outpatient facility as early as 15 weeks, when certain fetal structures are relatively easy to visualize. The test can be performed earlier or later, depending on the anomaly that is suspected; a vaginal version of ultrasound can also be performed even earlier in pregnancy. Sonography is considered safe and causes no discomfort for mother or fetus. A technician glides an instrument repeatedly over the mother's abdomen, generating a sound wave picture of the shape of the fetus and its internal structures, the placenta, and the umbilical cord. Although a sonogram is useful in diagnosing a wide range of fetal malformations, it cannot detect all such defects prenatally.

Amniocentesis

One of the most commonly performed prenatal tests, amniocentesis is the withdrawal of a small sample of the amniotic fluid surrounding the fetus. In addition to cushioning the fetus, amniotic fluid contains fetal cells normally sloughed off during the process of growth as well as other substances, such as alpha-fetoproptein (AFP), that provide important information about fetal health before birth. For example, analysis of the chromosomes in fetal cells collected during amniocentesis may reveal a chromosome abnormality such as trisomy 21 (Down syndrome) or other chromosome defects.

Amniocentesis is currently offered to all pregnant women who will be 35 and older at the time of delivery and to women with a personal or family history in themselves or their partners of a chromosome problem and to women at risk for a fetus with a genetic disorder, such as Tay-Sachs disease or thalassemia major, detectable by biochemical or DNA studies. Amniocentesis is also generally offered to women with abnormal maternal serum alpha fetoprotein (MSAFP) test results.

Amniocentesis is usually performed between the fifteenth and twentieth weeks (or sometimes earlier, depending on the physician) in an outpatient facility or physician's office. On occasion, the test will be performed later in pregnancy if a problem is suspected. Guided by ultrasound, the physician first locates the position of the fetus and placenta; he or she then inserts a thin hollow needle through the woman's abdomen into her uterus, well away from the fetus. About a tablespoon of amniotic fluid is withdrawn for analysis. Results generally take about 10 to 14 days. The test causes only slight discomfort, much like that experienced during blood drawing, and poses about 0.5 percent (1 in 200) risk of miscarriage. Women taking the test are advised to avoid strenuous physical activity for the remainder of the day on which the test is performed. Amniocentesis is also available to women with twin and triplet pregnancies. (For more information on amniocentesis, see Chapter 17.)

Chorionic Villus Sampling (CVS)

Because the results from amniocentesis testing are not available until the second trimester of pregnancy, there was an impetus for the development of a test that could detect genetic disorders early in pregnancy. CVS testing is generally performed about the tenth week of pregnancy. The physician inserts a thin needle through the abdominal wall (transabdominal CVS) or uses a narrow tube placed in the vagina for insertion through the cervix into the uterus (transcervical CVS). Instead of sampling amniotic fluid -- which is of low volume this early in pregnancy -- the syringe draws out a few of the tiny hair-like projections, or villi, that are part of the developing placenta. These villi contain fetal cells that can be analyzed for the presence of many genetic abnormalities, including chromosome problems. Results are usually available within 10 days. Rarely, amniocentesis may be required later to verify the results of CVS testing. CVS will not provide results for some conditions, such as neural tube defects. In the case of neural tube defect, MSAFP with sonography and/or amniocentesis are generally recommended.

CVS testing has certain advantages: If the test finds a chromosome problem or hereditary disorder and if the woman and her partner elect not to continue the pregnancy, she can have an abortion during the first trimester when it is safer and easier to obtain. In the future, a disorder discovered early in pregnancy by CVS testing may be treated in utero with medications, surgery, or even with gene replacement. Even today there are isolated situations in which early interventions can improve the health of the fetus (see below). In experienced hands, the risk of miscarriage with transabdominal CVS is about the same as in amniocentesis. A limited number of studies have suggested a causal relationship between CVS testing done earlier than 10 weeks and a rare malformation of the fingers and toes in newborns. The magnitude of this risk, if any, is quite small.

CVS testing is not as widely available as amniocentesis, although it is available in many major medical centers. Women with twin pregnancies can have CVS testing, but confirming amniocentesis may be required. Transcervical CVS testing generally is not advisable for women with a recent history of vaginal infection.

Techniques are now being developed to isolate fetal cells from the maternal circulation. In this way, fetal cells would be available for prenatal diagnosis without the need for amniocentesis or chorionic villus sampling. Prenatal diagnosis of the pre-implantation embryo is possible in special circumstances as part of in vitro fertilization.

Chromosome Analysis

Chromosome analysis is the examination of body tissues and/or blood samples under the microscope so that individual cells may be isolated and their chromosomes counted, specially stained (banded), and examined to investigate the possibility of a chromosome abnormality. About 1 in 200 newborns has some kind of chromosome alteration, although not all lead to problems. Many types of tissue may be used for chromosome analysis, including blood samples, skin cells, cells from amniotic fluid or chorionic villi, and fetal tissue from a miscarriage. Cells are cultured for a period of hours or days, depending on the type of tissue. They may be first stimulated by the addition of special chemicals to synthesize DNA and divide. Other chemicals are added to arrest the cells in a stage of cell division called metaphase and enhance the identification of the chromosomes. Cells are then photographed through the microscope, prints are made, and the individual chromosomes cut out and arranged in pairs, a process called karyotyping (See Fig. 14.2). Generally about 20 cells are counted and several karyotypes are done on the tissue sample in order to observe a consistent pattern in the number and configuration of the chromosomes.

DNA Testing

The identification of genes associated with diseases, as well as the discovery of DNA markers in the vicinity of those genes, has made available new diagnostic tests for a wide variety of genetic disorders. When the specific gene and its mutations are known at a DNA level, the gene can be detected using a specific test. Such a test has recently been developed for Huntington's disease, for example. This method is known as direct DNA analysis or direct gene detection, and examples of its use are the detection of sickle cell disease, the thalassemias, and cystic fibrosis. On the other hand, when the gene has not been isolated and analyzed for alterations, genetic markers alongside the suspected gene must be identified, a process known as indirect detection or linkage analysis. A current example of linkage analysis is the DNA test for adult polycystic kidney disease. It is usually necessary to test several members of a family to trace the presence of the linked marker and to identify susceptible individuals. With the recent identification of the gene on chromosome 16, however, direct gene detection may be possible soon.

DNA testing can be performed using any tissue sample containing DNA, for example, white blood cells, skin cells, amniotic fluid cells, or chorionic villi. There are numerous commercial, university, and hospital-based laboratories specializing in DNA testing. Confidentiality of test results is safeguarded. DNA banking, the storage of DNA from tissue samples, may aid in later diagnosis of a genetic condition in a family member when the gene for a particular disorder is identified or new mutations are discovered, often long after the affected individual has died.

Newborn Screening

A genetic screening test is one that is performed on an entire population, or subset of a population, for the purpose of identifying individuals at risk for certain genetic disorders. An example already mentioned is MSAFP screening in pregnancy. In the United States, newborn screening is now conducted in every state in order to identify babies with certain genetic or metabolic disorders that can be treated shortly after birth, even before symptoms appear.

The list of conditions screened depends upon the populations at risk and other public health considerations. For example, all states screen newborns for phenylketonuria (PKU), a recessively inherited disorder of metabolism characterized by elevated levels of the amino acid phenylalanine and resulting in mental retardation if untreated. Fortunately, a phenylalanine- restricted diet beginning soon after birth can insure normal development. Sickle cell disease is another condition included in newborn screening protocols in many states. As with PKU, early identification of babies who have sickle cell disease can allow for early treatment, such as daily penicillin to decrease the threat of bacterial infection, education of the parents, and amelioration of complications of the disease. Newborn screening also identifies infants who carry the sickle cell trait, enabling parents, with the help of genetic testing and counseling, to understand their chances of having future children with sickle cell disease.

A third example is newborn screening for congenital hypothyroidism, a problem with the normal development of the thyroid gland affecting about 1 in every 3,000 newborns (see Chapter 29). Timely treatment with thyroid hormone can prevent the onset of mental retardation that may result from this condition. In newborn screening, a few drops of blood are taken from the baby's heel within several days after birth. Results are sent to the physician or hospital caring for the family. Any infant with an abnormal result is retested to confirm the initial result. If the abnormal result is confirmed, the baby will be referred by the hospital or pediatrician for special care soon after birth. In some states, only abnormal results are reported to the parents; those parents wishing to know the outcome of newborn screening, even if results are normal, may have to contact their physician or the hospital where the baby was born.

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Confronting Difficult Decisions in Genetics

As new medical technologies become available to provide additional information on which to base decision- making about health, studies have shown that people tend to make use of them. This does not always hold true for new technologies in the field of genetics, however. Choosing new knowledge in this field may open the way for even more difficult choices, such as whether to undergo prenatal testing and whether to continue a pregnancy with an affected fetus. Another difficult choice may be deciding whether to be tested for certain genetic conditions before they are symptomatic, especially if the outcome of the disorder may be severe or fatal.

Deciding For or Against Prenatal Testing

For some women, especially those from certain religious or cultural backgrounds, accepting prenatal testing may suggest the possibility of abortion. Under these circumstances, some women and their partners may decline prenatal testing and simply accept whatever risks are likely. Women who decline prenatal testing, for whatever reason, may still worry about the outcome of the pregnancy and will benefit from the support of family members and the genetic counselor while they wait.

For many other women, however, the choice is not so simple: They may choose prenatal testing and then be faced with deciding whether or not to continue the pregnancy based on the information revealed by the tests. More often than not, results are normal and they experience relief after learning that the condition tested for is not likely to occur.

A decade ago, prenatal tests such as amniocentesis offered little hope for treatment of a genetic condition in utero or shortly after birth. Increasingly, prenatal testing can diagnose conditions that are treatable and, in some cases, even curable. The science of genetics is moving so rapidly that gene therapy and other treatments for many genetic conditions are likely to be available within the next few years, making abortion only one of a range of available options.

Even when genetic conditions diagnosed prenatally cannot be treated, parents often gain valuable time to prepare themselves emotionally and practically for the birth of a child with special needs. Prenatal diagnosis may also provide information that can alter the management of the rest of the pregnancy, the mode of delivery, and the care of the baby in the first few days of life.

Deciding Whether to End a Pregnancy

When prenatal diagnosis reveals an abnormality in the fetus, both parents experience feelings of grief for the loss of the healthy baby they had hoped for. While some couples may have the support of their families during this crisis, others may feel distanced from family members who may have their own feelings about the abnormal fetus, as well as about a possible abortion. The couple may even decide to keep the news from family members and friends. This tends to further isolate the parents who may then rely on the obstetrician or nurse-midwife, the genetic counselor, and/or a member of the clergy for emotional support while they move toward a decision about the pregnancy.

It is important to recognize that deciding to end a pregnancy after prenatal diagnosis of a serious fetal anomaly or genetic condition can be agonizing for parents. For one thing, having conceived a child with a serious health problem can deal a severe blow to any parent's sense of self-esteem, especially if one parent feels responsible for having caused the birth defect by transmitting the gene causing the problem. The couple may not even agree between themselves on whether to end the pregnancy. Moreover, a decision to abort, while sometimes in conflict with the parents' moral values or religious beliefs, may be influenced by the wish to spare the family the heartbreak or the expense of raising a child with a serious genetic disease or birth defect. This can engender further guilt. Most difficult of all is the fact that for many couples, this pregnancy has been planned and its potential loss represents the loss of a desired child.

Willingness to abort an affected fetus seems to vary with the perceived seriousness of the problem. Parents may need to gather information on treatment and prognosis of the condition and to meet a child or family with this condition to help them arrive at a decision. Several studies have shown that more women would consider aborting a fetus with severe mental retardation, while fewer would abort for a serious physical disability. Other studies show that when parents already have a child with the disorder, they are less likely to decide to abort an affected fetus.

It is also difficult to decide not to end the pregnancy. Some women may not believe the results of prenatal diagnosis, may fear the abortion procedure itself, or may be opposed to abortion altogether. Continued support from the medical team and the availability of information and support groups can help women and their partners to prepare for the delivery and the care of their infant after birth.

Women and their partners who must make these decisions need the kind of supportive, nondirective guidance that genetic counseling can provide. This kind of supportive approach should begin at the first meeting and well before the diagnosis is made known to the parents. One recent study from the University of Rochester Genetic Counseling Center encouraged women participants to describe their experiences and needs and to allow these descriptions to be recorded on tape. Most of the women stressed the need for a counselor to be present with the couple when they received the news, to provide both emotional support and information to help them begin to deal with the reality and urgency of the situation. Even those women who were not opposed to abortion per se required a great deal of time to make what for some may have been the most difficult decision of their lives.

Once the decision for or against abortion has been made, the Rochester study found, women and their partners who worked with supportive counselors, such as genetics professionals, members of the clergy, or social workers, needed to continue that relationship through the delivery or termination and beyond. In the case of a second trimester abortion, this support was particularly crucial. Some of the women reported experiencing difficulty dealing with hospital personnel whom they perceived as critical of their decision. Yet, while many women initially experienced ambivalence and loss after ending the pregnancy, with time most felt they had made the correct choice. Many are eased through this period of adjustment by continued contact with the counselor and by participation in pregnancy loss support groups. These groups help women and their partners come to terms with their loss and look toward the future, hopefully to the birth of a healthy baby.

For women who choose to deliver a child known by prenatal testing to have a genetic condition or birth defect, groups made up of parents dealing with a similar problem can provide invaluable emotional support and enable the sharing of coping strategies. While not all parents are ready to join a support group, those who do join report experiencing the relief of expressing feelings they could not share with family members and friends. They also experience the added benefit of being able to listen with empathy and provide practical help to others confronting the same diagnosis. Many are also active in raising funds for research and raising awareness through public and professional education campaigns. There are more than 150 support organizations for specific genetic diseases and birth defects; names and addresses can be obtained by contacting the Alliance of Genetic Support Groups or one of the other organizations listed at the end of this chapter.

Deciding Whether to Be Tested for Genetic Conditions Before They Are

Symptomatic Genetic tests that can predict whether we will develop certain diseases in adulthood are quite different from prenatal tests because they forecast our own genetic futures and those of our relatives, sometimes without the ameliorating effect of available treatment or cure. Choosing to be tested for Huntington's disease, for example, an uncommon but fatal degenerative neurological disease inherited in an autosomal dominant pattern, means the person being tested has to choose between profound relief if the gene is not found and knowledge of eventual decline and death from the disease if it is found. This is not a choice easily made, because the burden of knowing may be very great and may cause considerable psychological distress in those who receive an unfavorable report. Huntington's disease appears in middle age, often after families have been formed. Any child of a person with the gene is at a 50 percent risk of inheriting it. To date, few families where the Huntington's gene appears have taken advantage of presymptomatic testing. Nevertheless, a recent Canadian study found that when a group of participants at risk for Huntington's disease was counseled, both before and after testing, just getting a result -- either favorable or unfavorable -- gave them some relief from the agony of uncertainty and increased their psychological well-being. Another choice faces families affected by diseases such as adult polycystic kidney disease or familial hypercholesterolemia, in which presymptomatic diagnosis allows for close medical follow-up and early treatment. With the availability of new DNA tests for single-gene disorders, more individuals and families will be asked to choose whether to get tested. Although it is hard to know how many will decide that knowing is better than not knowing, the results of these tests can often lead to preventive strategies to reduce the effects of the disease and to prolong healthy life.

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Looking to the Future: Ethical Issues in Genetics

As new discoveries in genetics continue to stimulate hopes for the future treatment and prevention of a host of hereditary disorders, they also raise troubling questions about who should have access to genetic information about individuals who are tested for those disorders. The 1992 March of Dimes Birth Defects Foundation study cited earlier in this chapter found that 57 percent of the 1,000 Americans polled thought that others besides the person tested had a right to know whether a genetic defect had been found. Of these, 58 percent said insurers had a right to the information and 33 percent thought employers should also have the information.

The results of this survey have troubled experts in medical ethics because they are inconsistent with experience. Two decades ago the availability of a hemoglobin test for sickle cell was followed by widespread misuse of the information -- by employers, the insurance industry, and the military -- to the detriment of people with the disease as well as carriers of sickle cell trait, most of whom were African-Americans. More recently, the experience with AIDS has shown that the potential for abuse of information made available through testing is still with us: Many Americans have had their coverage reduced, their claims denied, or their policies eliminated altogether when insurers learned of their HIV status. The situation is similar for millions more Americans with other chronic conditions, and a significant number of cases of discrimination based solely on genetic makeup have already been reported. In the workplace, despite the recent enactment of the Americans with Disabilities Act, there is concern about whether companies will begin to use genetic testing as a way to avoid hiring employees with the potential for costly hereditary illnesses. Although laws have been enacted in a number of states barring discrimination based on the results of genetic tests, many of these laws apply only to carriers of specific conditions, such as sickle cell disease, Tay-Sachs disease, or cystic fibrosis. Several states have already shown interest in drafting legislation to offer wide protection to Americans who choose genetic testing.

The availability of DNA tests to identify carriers of common diseases such as cystic fibrosis and their potential use in population screening poses another kind of concern. In an economy characterized by shrinking resources for social welfare, will pressure be applied to families at risk for an inherited disease to undergo prenatal testing and selective abortion should the fetus be affected? We already know that some couples may consider ending a pregnancy after an abnormal prenatal test not because they do not want the child, but because of concern that the societal supports for raising such a child -- adequate schooling, health insurance, future employment opportunities -- may not be available to them.

Underlying the solutions to these and other ethical concerns is the need for acceptance of the idea of genetic variability, the notion that each of us has among our estimated 100,000 genes a certain number that predispose us to one condition or another. But our genes are not necessarily our destiny: Those of us who are born with certain defects or develop certain conditions may be only mildly affected; those severely affected may lead exemplary lives, accomplish much, and may ultimately benefit from improved treatments. In the end, the considerable advances in genetics we are witnessing may lead us to an appreciation of the contributions made by all of us -- regardless of the genes we carry -- to the variety of the human experience.

New Treatment Options for Genetic Disorders

While new possibilities for treatment raise the hopes of families already living with a genetic disorder, they may also generate some concern about whether or not to try them, how successful they are likely to be, and what risks they may entail. A recent national survey conducted by the March of Dimes Birth Defects Foundation (1992) revealed that many Americans felt somewhat uneasy about the idea of gene therapy and even misunderstood its basic purpose: to help people overcome genetic disease rather than to change physical characteristics of normal individuals. Nearly three-quarters of those surveyed favored strict government regulation of the practice.
Trials for some of these new treatments, such as gene therapy, are just beginning. Gene therapy affects only the health of the individual being treated and does not prevent future generations from inheriting the condition. For example, not long ago, a patient with familial hypercholesterolemia was injected with cells -- taken from her own liver -- that had been supplied in the laboratory with a gene she lacked. The missing gene is responsible for directing the production of a receptor protein that acts as a sponge for harmful cholesterol in the body. Researchers hope that the genetically altered cells will multiply in her liver and result in a dramatic lowering of cholesterol levels. Similarly, in cystic fibrosis, scientists have devised a way to deliver the normal gene for a protein that controls salt balance in the body. (In people with cystic fibrosis, the abnormal gene causes the build-up of thick mucus in the lungs.) Researchers have packaged this gene in a specially treated cold virus delivered through a patient's airways. In a manner similar to the previous example, they are hoping that the normal gene will replicate in just enough airway tissue to prevent mucus build-up and reduce symptoms.
Although gene therapy may still be in the experimental stages, other treatments for genetic conditions are already reporting successes. For example, in some people with type I Gaucher disease, intravenous replacement of the missing enzyme, glucocerebrosidase, has resulted in a significant lowering of fatty deposits stored in the liver. Enzyme replacement also results in a reduction of the size of the liver and spleen, usually greatly enlarged in this disease. There is still more to be learned about how much enzyme should be given and how long treatment should go on. Nevertheless, it is now likely that enzyme replacement therapy will be tried in other inherited metabolic disorders. Other therapies, such as bone marrow or organ transplantation, can be life-saving in certain genetic conditions.

Some genetic disorders can even be treated in utero. For example, congenital adrenal hyperplasia (CAH), an autosomal recessive condition resulting in masculinization of the external genitalia of female fetuses during gestation, can be treated successfully by giving oral corticosteroids to the mother during pregnancy. This preventive treatment decreases the need for surgery on the infant after birth. Women with phenylketonuria (PKU) who were treated successfully with dietary restriction of phenylalanine during infancy and childhood to prevent mental retardation still have a high incidence of mental retardation and other birth defects in their own newborns, who are not affected by PKU. However, continuing restriction of phenylalanine in the diets of these women before and during pregnancy to lower fetal exposure to phenylalanine can actually reduce the frequency of these problems.
Other treatments hold out the promise of primary prevention of some genetic conditions. A prime example is the use of folic acid (one of the eight B vitamins) before conception and very early in pregnancy to prevent neural tube defects such as meningomyelocele and anencephaly. Prior studies showed that folic acid substantially lowers the risk of neural tube defects recurring in a family where one child has already been born with such a defect. In a recent controlled study of the use of a vitamin supplement containing folic acid compared with a trace element supplement taken before conception and early in pregnancy, folic acid dramatically reduced the incidence of these defects in families with no prior history. As a result of these and other studies, the
U.S. government is actively considering whether to fortify flour and other foods with folic acid. The current recommendation is that all women during childbearing years take a daily supplement containing at least the recommended allowance of 0.4 mg of folic acid per day, in addition to the folic acid contained in leafy green vegetables, dried beans, liver, and some citrus fruits. For women who have already had a child with a neural tube defect, higher amounts of folic acid are recommended when considering a pregnancy. See your doctor for advice.