Genetics and Genetic Counselling
Genetics and Genetic Counselling
Genetics and Genetic Counselling
generation to the next. They result from some disorder in gene or chromosome
structure and occur in 5% to 6% of newborns.
o Genetics is the study of heredity and the variation of inherited characteristics
o Cytogenetics is the study of chromosomes by light microscopy and the
method by which chromosomal aberrations are identified.
A. Nature of Inheritance
o Genes are the basic units of heredity that determine both the physical
and cognitive characteristics of people. It is composed of segments of
DNA; they are woven into strands in the nucleus.
o Chromosomes are threadlike structures of nucleic acids and proteins
found in the nucleus of most living cells, carrying genetic information
in the form of genes
o In humans, each cell, except for the sperm and ovum, contains 46
chromosomes (22 pairs of autosomes and 1 pair of sex chromosomes).
Spermatozoa and ova each carry only half of the chromosome number or
23 chromosomes. For each chromosome in the sperm cell, there is a like
chromosome of similar size shape, and function (autosome, or
homologous chromosome) in the ovum. Because genes are always
located at fixed positions on chromosomes, two like genes (alleles) for
every trait are represented in the ovum and sperm on autosomes. The
one chromosome in which this does not occur is the chromosome for
determining gender.
o If the sex chromosomes are both type X (large symmetric) in the zygote
formed from the union of a sperm and ovum, the individual is female. If
one sex chromosome is an X and one a Y (a smaller type), the individual is
a male.
o A person’s phenotype refers to his or her outward appearance or the
expression of genes.
o A person’s genotype refers to his or her actual gene composition. It is
impossible to predict a person’s genotype from the phenotype or
outward appearance.
o A person’s genome is the complete set of genes present
o A normal genome is abbreviated as 46XX or 46XY.
B. Mendelian Inheritance: Dominant and Recessive Patterns
o The principles of genetic inheritance of disease are the same as those
that govern genetic inheritance of other physical characteristics, such as
eye or hair color. These principles were discovered and described by
Gregor Mendel, an Austrian naturalist, in the 1800s and are known as
Mendelian laws.
o Homozygous traits are two like chromosomes (one from the mother
and one from the father)
o Heterozygous traits occur when the genes differ (a healthy gene from
o the mother and an unhealthy gene from the father, or vice versa)
o Dominant genes are always expressed in preference to the recessive
genes. For example, a gene for brown eyes is dominant over one for
blue eyes which is recessive; a child is born with a gene for brown
eyes and a recessive one for blue eyes will have brown eyes.
o An individual with two homozygous genes for a dominant trait is said to
be homozygous dominant; an individual with two genes for a recessive
trait is homozygous recessive.
If the father has the disease and chooses a sexual partner who is free of the
disease gene, the chances are 100% that a daughter will have the sex linked
recessive gene, but there is no chance that a son will have the disease (see
Fig. 9).
2. Deletion Abnormalities
o Deletion abnormalities are a form of chromosome disorder in which
part of a chromosome breaks during cell division, causing the affected
person to have the normal number of chromosomes plus or minus an
extra portion of a chromosome, such as 45.75 chromosomes or 47.5.
a. Cri-du-chat syndrome (46XY5P-)
- In cri-du-chat syndrome (46XY5q_), one portion of
chromosome 5 is missing.
Abnormal cry (sound of a cat than a human)
Small head
Wide-set eyes
Downward slant palpebral fissure of the eye
Recessed mandible
Severely cognitively challenge
b. Fragile X Syndrome (46XY23Q-)
- Fragile X syndrome is the most common cause of cognitive
challenges in males. It is an X-linked disorder in which on long
arm of an X chromosome is defective, which results in
inadequate protein synaptic responses. The incidence of the
syndrome is about 1 in 4,000 males. The following are the
characteristics of a boy with Fragile X syndrome:
Hyperactivity, aggression, or autism
Reduced intellectual functioning, with marked deficits in
speech and arithmetic
Large head, long face with high forehead
Prominent lower jaw
Large protruding ears
Obesity
Hyper extensive joints
Cardiac disorders
After puberty: enlarged testicles; fertile and can reproduce
Carrier females may show evidence of physical and
cognitive characteristics.
- Management
Stimulants, atypical antipsychotics, serotonin reuptake
inhibitors may improve symptoms of poor
concentrations and impulsivity
3. Translocation Abnormalities
o Translocation abnormalities are perplexing situations in which a child
gains an additional chromosome through another route. A form of Down
syndrome occurs as an example of this.
o In this instance, one parent of the child has the correct number of
chromosomes (46), but chromosome 21 is misplaced; it is abnormally
attached to another chromosome, such as chromosome 14 or 15.
o The parent’s appearance and functioning are normal because the total
chromosome count is a normal 46. He or she is termed a balanced
translocation carrier.
o If, during meiosis, this abnormal chromosome 14 (carrying the extra 21
chromosomes) and a normal chromosome 21 from the other parent are
both included in one sperm or ovum, the resulting child will have a total
of 47 chromosomes because of the extra number 21. Such a child is said
to have an unbalanced translocation syndrome. The phenotype
(appearance) of the child will be indistinguishable from that of a child
with the form of Down syndrome that occurs from simple
nondisjunction.
4. Mosaicism
o Mosaicism is an abnormal condition that is present when the
nondisjunction disorder occurs after fertilization of the ovum, as
the structure begins mitotic division (in simple nondisjunction,
uneven cell division occurs during meiosis.
o If this occurs, different cells in the body will have different chromosome
counts. The extent of the disorder depends on the proportion of tissue
with normal chromosome structure to tissue with abnormal
chromosome constitution.
o Children with Down syndrome who have near-normal intelligence
may have this type of pattern.
o The occurrence of such a phenomenon at this stage of development
suggests that a teratogenic (harmful to the fetus) condition, such as x-ray
or drug exposure, existed at that point to disturb normal cell division.
This genetic pattern in a female with Down syndrome caused by
mosaicism would be abbreviated as 46XX/47XX21_ to show that some
cells contain 46 and some 47 chromosomes.
5. Isochromosomes
o If a chromosome accidentally divides not by a vertical separation but by a
horizontal one, a new chromosome with mismatched long and short arms
can result. This is an isochromosome. It has much the same effect as a
translocation abnormality when an entire extra chromosome exists.
a. Karyotyping.
For karyotyping, a sample of peripheral venous blood or a scraping of cells
from the buccal membrane is taken. Cells are allowed to grow until they
reach metaphase, the most easily observed phase. Cells are then stained,
placed under a microscope, and photographed. Chromosomes are
identified according to size, shape, and stain; cut from the photograph,
and arranged. Any additional, lacking, or abnormal chromosomes can be
visualized by this method.
A newer method of staining, FISH, allows karyotyping to be done
immediately, rather than waiting for the cells to reach metaphase. This
makes it possible for a report to be obtained in only 1 day. Fetal skin cells
can be obtained by amniocentesis or CVS. A few fetal cells circulate in the
maternal bloodstream, most noticeably trophoblasts, lymphocytes, and
granulocytes.
They are present but few during the first and second trimesters but
plentiful during the third trimester. Such cells can be cultured and used for
genetic testing for such disorders as trisomies.
b. Chorionic Villi Sampling.
CVS is a diagnostic technique that involves the retrieval and analysis of
chorionic villi from the growing placenta for chromosome or DNA analysis.
The test is highly accurate and yields no more false-positive results than
does amniocentesis.
c. Amniocentesis.
Amniocentesis is the withdrawal of amniotic fluid through the abdominal
wall for analysis at the 14th to 16th week of pregnancy. Because amniotic
fluid has reached about 200 mL at this point, enough fluid can be
withdrawn for the karyotyping of skin cells found in the fluid as well as an
analysis of AFP or acetylcholinesterase. If no acetylcholinesterase, a
breakdown product of blood, is found in the specimen, it confirms that an
elevated AFP level is not a false-positive reading caused by blood in the
fluid. For the procedure, a pocket of amniotic fluid is located by
ultrasound.
Then a needle is inserted transabdominal, and about 20 mL of fluid is
aspirated. Skin cells in the fluid are karyotyped for chromosomal number
and structure. The level of AFP is analyzed. Some disorders, such as Tay-
Sachs disease, can be identified by the lack of a specific enzyme, such as
hexosaminidase A, in amniotic fluid.
Amniocentesis has the advantage over CVS of carrying only a 0.5% risk of
spontaneous miscarriage. Unfortunately, it usually is not done until the
14th to 16th week of pregnancy. This may prove to be a difficult time
because, by this date, a woman is beginning to accept her pregnancy and
bond with the fetus. In addition, termination of pregnancy during the
second trimester is more difficult than during a first trimester. Support
women while they wait for test results and to make a decision about the
pregnancy. Women with a Rh-negative blood type need Rh immune
globulin administration after the procedure to protect against
isoimmunization in the fetus. All women need to be observed for about 30
minutes after the procedure to be certain that labor contractions are not
beginning and that the fetal heart rate remains within normal limit.
an
d
mi
cro
del
eti
ons
in
fet
al
D
N
A
Chorionic villi 10-12 Biopsy of placenta Invasive, risk
Diagnostic test sampling weeks
of for karyotype
1111scainage
Maternal 15-20 Maternal blood Noninvasive,
Screening test quadruple weeks
draw maternal for Down marker
screen blood draw
syndrome,
trisomy 18
and 13
Amniocentesis 15-18 Collection of Invasive, risk
Diagnostic for weeks amniotic fluid
of fetal
containing fetal 1111sca1nage
show
through maternal common
abdomen chromosomal
disorders that
can be diagnosed
through amniocentesis.
Table 4. Common Genetic Disorders that can be detected by maternal serum, amniocentesis, or
chorionic villus sampling
d. Levels of four substances in pregnant women's blood (Quadruple
screening) during 15-18 weeks of pregnancy (Table 5)
1. Alpha-fetoprotein (AFP), a protein made by the developing baby
2. Human chorionic gonadotropin (HCG), by the placenta
3. Estriol, a hormone made by the placenta and the baby's liver
4. Inhibin A, by
the placenta
Table 5
B. Nursing Diagnosis
Typical nursing diagnoses related to the area of genetic disorders include:
1. Decisional conflict related to testing for an untreatable genetic disorder
2. Fear related to the outcome of genetic screening tests
3. Situational low self-esteem related to identified chromosomal abnormality
4. Deficient knowledge related to the inheritance pattern of the family’s inherited
disorder
5. Health-seeking behaviors related to the potential for genetic transmission of
disease
6. Altered sexuality pattern related to fear of conceiving a child with a genetic
disorder
C. Outcome Identification and Planning
Outcome identification and planning for families undergoing genetic assessment
differ according to the types of assessments performed and the results obtained. This
may include determining what information the couple needs to know before testing
can proceed or helping couples arrange for further assessment measures. Be certain
that goals are realistic and consistent with the individual’s or couple’s lifestyle (not all
people want to be totally
informed about family illnesses).
D. Implementation
Parental reactions to the knowledge that their child has a possible genetic
disorder or to the birth of a child with a genetically inherited disorder usually involve
a grief reaction, similar to that experienced by parents whose child has died at birth
(their “perfect” child is gone). Both parents may pass through stages of:
1. Shock and denial (“This cannot be true”),
2. Anger (“It’s not fair that this happened to us”),
3. Bargaining (“If only this would go away”)
4. Acceptance (“It has happened to us and it is all right”).
For some couples, a genetic disorder is diagnosed during the pregnancy; for others, it
may not be discovered until birth, or possibly not even until the child is of school age.
For these parents, the reaction will occur at that later point of diagnosis.
E. Outcome Evaluation
Examples of expected outcomes for a family with a known genetic disorder might be:
1. The couple states they feel capable of coping no matter what the
outcome of genetic testing.
2. The client accurately states the chances of a genetic disorder occurring in her next
child.
3. The couple states they have resolved their feelings of low self-esteem
related to the birth of a child with a genetic disorder.
A couple’s decisions about genetic testing and childbearing can change over time.
For example, a decision made at age 25 not to have children because of a potential
genetic disorder may be difficult to maintain at age 30, as the couple sees many of
their friends with growing families. Be certain that such couples have the telephone
number of a genetic counselor. Urge them to call periodically for news of recent
advances in genetic screening techniques or disease treatments so they can remain
current and well-informed for future planning.