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
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.
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.
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:
The
diagram below shows a pedigree of a family with several members who have
Huntington's disease. (See Fig.
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.
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
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
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
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
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
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
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
Other
much rarer chromosomal abnormalities also become more prevalent as maternal age
increases. These include trisomy
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
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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 Since
virtually all obstetricians are now offering their pregnant patients maternal
serum screening at about |
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
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
Cytomegalovirus: One in every
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
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
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
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
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.
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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.
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Genetic Deafness More
than half of all childhood deafness can be traced to genetic causes. Close to
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 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.
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.
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
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
Amniocentesis
is currently offered to all pregnant women who will be
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
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
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
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
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
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
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
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
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
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
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
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
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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 ( 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. |