Friday, November 19, 2010

Maternal and Child Health Nursing Chapter 7

Chapter 7
Genetic Assessment and Counseling
Key Terms
  • alleles
  • chromosomes
  • dermatoglyphics
  • dominant gene
  • genes
  • genetics
  • genome
  • genotype
  • heterozygous
  • homozygous
  • imprinting
  • karyotype
  • meiosis
  • nondisjunction
  • phenotype
  • recessive gene
Objectives
After mastering the contents of this chapter, you should be able to:
  • Describe the nature of inheritance, patterns of recessive and dominant mendelian inheritance, and common chromosomal aberrations such as nondisjunction syndromes.
  • Assess a family for the probability of inheriting a genetic disorder.
  • Formulate nursing diagnoses related to genetic disorders.
  • Establish expected outcomes that meet the needs of the pregnant family undergoing genetic assessment and counseling.
  • Plan nursing care related to an alteration in genetic health, such as assisting with an amniocentesis.
  • Implement nursing care related to identification of or counseling for a genetic disorder.
  • Evaluate expected outcomes for achievement and effectiveness of nursing care.
  • Identify National Health Goals and specific measures related to genetic disorders that nurses can help the nation achieve.
  • Identify areas related to genetic assessment that could benefit from additional nursing research or application of evidence-based practice.
  • Use critical thinking to analyze ways that nurses can contribute to health education and family-centered counseling for genetic issues.
  • Integrate knowledge of genetic inheritance with nursing process to achieve quality maternal and child health nursing care.
Amy Alvarez is a woman you meet at a genetic counseling center. She was adopted as a newborn and never felt a need to locate her birth parents because her adoptive parents provided a “close to perfect” childhood for her. After college, she married the most eligible bachelor in her hometown. She is now pregnant with her first child. At 15 weeks into the pregnancy, she has been advised her child may have translocation Down syndrome. She asks you, “Why is this happening? There's no disease like this in either of our families.”
Previous chapters described techniques for caring for women and their families preparing for childbearing and childrearing. This chapter discusses the basic principles by which disorders are inherited and information about the necessary assessments, care, and guidelines for counseling of the woman and her family if it is discovered that there is a possibility of a genetic disorder in a child. This is important information, because it can influence the health of a family for generations to come.
How would you answer Amy?
After you've studied this chapter, access the accompanying website. Read the patient scenario and answer the questions to further sharpen your skills, grow more familiar with RN-CLEX types of questions, and reward yourself with how much you have learned.
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As many as 1 in 20 newborns inherits a genetic disorder. More than 30% of pediatric hospital admissions are for genetic-influenced disorders (Ward, 2003). The possibility that a child could have a genetic disorder crosses the minds of most pregnant women and their partners at some point in a pregnancy, whether or not there is any family history of genetic disorders. Many pregnant couples ask health care providers about their chances of having a child with a genetic disorder and about genetic testing, because advances in screening techniques have made genetic testing a common feature of prenatal care. The importance of the Human Genome Project and the necessity to improve techniques of screening for genetic disorders have become a national priority (Box 7.1). Nurses can be instrumental in fostering the achievement of these goals (Siegel & Milunsky, 2004).
Women are offered routine screening of maternal serum levels of alpha-fetoprotein (MSAFP) early in pregnancy to evaluate for neural tube or chromosomal disorders in the fetus. Chorionic villi sampling (CVS) and amniocentesis are follow-up techniques that may be offered to women who are older than 35 years of age, and to those whose MSAFP level is abnormal, to further screen for genetic disorders. Couples who already know of the existence of a genetic disorder in their family and those who have had a previous child born with a congenital anomaly require still additional, more extensive testing. After a positive test for a genetic disorder, they will almost certainly undergo an emotional period of decision making as they decide how to prepare for an ill child or make a decision to end the pregnancy. Informative and sensitive genetic counseling by health care providers educated in the specialty of genetics is essential for these couples. Because most screening takes place in an ambulatory setting, a nurse can play a vital role as educator, supporter, and communicator for the family (Pelchat et al., 2004).
Nursing Process Overview
For Genetic Assessment and Counseling
Assessment
Assessment is a crucial step in any nursing intervention, but it plays an especially vital role in genetic screening and counseling. Assessment measures include a detailed family history, physical examination of both the parents and the affected child, and an ever-growing series of laboratory assays of blood, amniotic fluid, and maternal and fetal cells. Nurses serve as members of genetic assessment and counseling teams in many roles, especially when helping to obtain the initial family history, assisting with the preliminary physical examination, obtaining blood serum for analysis, or assisting with procedures such as amniocentesis.
Nursing Diagnosis
Typical nursing diagnoses related to the area of genetic disorders are the following:
  • Decisional conflict related to testing for an untreatable genetic disorder
  • Fear related to outcome of genetic screening tests
  • Situational low self-esteem related to identified chromosomal abnormality
  • Deficient knowledge related to inheritance pattern of the family's inherited disorder
  • Health-seeking behaviors related to potential for genetic transmission of disease
  • Altered sexuality pattern related to fear of conceiving a child with a genetic disorder
Outcome Identification and Planning
Outcome identification and planning for families involved with genetic assessment differ according to the types of assessments performed and the results obtained. They may include determining what information the couple needs to know before testing can proceed or helping couples to arrange for further assessment measures during a pregnancy. Goals must be realistic and consistent with the individual's or couple's lifestyle (not all people want to be totally informed about family illnesses).
Implementation
Parental reaction to the knowledge that their child has a possible genetic disorder or to the birth of a child with a genetically inherited disorder usually involves a grief reaction, similar to that experienced by parents whose child has died at birth. Both parents must work through the stages of shock and denial (“This cannot be true”), anger (“It's not fair that this happened to us”), and bargaining (“If only this would go away”) to reorganization and acceptance (“It has happened to us and it is all right”). For some couples, a genetic disorder is diagnosed during the pregnancy; it may not be discovered until birth, or possibly not even until the child is of
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school age. For these parents, the reaction will occur at that later point of diagnosis.
As a rule, when parents are under stress, it is most helpful to guide them to concentrate on short-term goals and actions. Help them look first at the immediate needs of their family, the fetus, and the newborn, and later on at what type of continued follow-up will be necessary. For instance, after the birth, will the baby need to be hospitalized for immediate surgical correction of accompanying congenital anomalies, or will the parents be able to take the baby home? These decisions must be made immediately. What kind of special schooling the child will need is a decision that can wait until a later date.
Identifying support people who can be helpful to the parents during their time of disorganization and shock is also important. These people may be the usual family resources, such as grandparents or other family members. In some families, these people are as disturbed by the diagnosis as the parents and therefore cannot offer their usual support. Secondary support sources may be necessary, including organizations such as the March of Dimes Birth Defects Foundation (http://www.marchofdimes.com), the American Association of Klinefelter Syndrome Information and Support (http://www.AAKSIS.org), the National Fragile X Foundation (http://www.NFXF.org), the National Down Syndrome Society (http://www.ndss.org), and the Turner Syndrome Society (http://www.Turner-syndrome-us.org). Not all parents are ready to talk to members of such organizations at the time of diagnosis. To join such an organization may make the diagnosis seem “real” or move them out of denial before they are ready.
Identifying health care personnel and ensuring clear communication among health care providers with whom the parents will need to maintain contact during the next few months can offer additional support. Ensuring that the parents have health care providers they know they can turn to, especially when they are moving out of denial, helps them move forward.
Outcome Evaluation
Examples of expected outcomes for a family with a known genetic disorder include the following:
  • Couple states they feel capable of coping no matter what the outcome of genetic testing.
  • Client accurately states the chances of a genetic disorder occurring in her next child.
  • Couple states they have resolved their feelings of low self-esteem related to birth of a child with a genetic disorder.
A couple's decisions about genetic testing and childbearing may 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. Individuals and couples who have asked for genetic counseling should be given the phone number of a genetic counselor and urged to call periodically for news of recent advances in genetic screening techniques or disease treatments, so they can remain current.
Genetic Disorders
Inherited or genetic disorders are disorders that can be passed from one generation to the next. They result from some disorder in gene or chromosome structure. Genetics is the study of the ways such disorders occur.
Genetic disorders can occur at the moment an ovum and sperm fuse or even earlier, in the meiotic division phase of the gametes (ovum and sperm). Some genetic abnormalities are so severe that normal fetal growth cannot continue. This results in early spontaneous abortion. Genetic disorders are so common that as many as 50% of first-trimester spontaneous miscarriages may be the result of chromosomal abnormalities (Ward, 2003). Other genetic disorders do not affect life in utero, so the result of the disorder becomes apparent only at the time of fetal testing or after birth. In the near future, it may be possible not only to identify aberrant genes for disorders but also to insert healthy genes in their place using stem cells. Gene replacement therapy is encouraging in the treatment of blood, spinal cord, and immunodeficiency syndromes (Jones et al., 2003).
Nature of Inheritance
Genes are the basic units of heredity that determine both the physical and cognitive characteristics of people. Composed of segments of DNA (deoxyribonucleic acid), they are woven into strands in the nucleus of all body cells to form chromosomes.
In humans, each cell, with the exception of the sperm and ovum, contains 46 chromosomes (44 autosomes and 2 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 and 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 sex. 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 (Fig. 7.1A). If one sex chromosome is an X and one a Y (a smaller type), the individual is a male (Fig. 7.1B).
A person's phenotype refers to his or her outward appearance or the expression of the genes. A person's genotype refers to his or her actual gene composition. A person's genome is the complete set of genes present (about 50,000 to 100,000). A normal genome is abbreviated as 46XX or 46XY (designation of the total number of chromosomes plus a graphic description of the sex chromosomes present). If a chromosomal aberration exists, it is listed after the sex chromosome pattern. In such abbreviations, the letter p stands for short arm defects and q stands for defects on the long arm of the chromosome. The abbreviation 46XX5p–, for example, is the abbreviation for a female with 46 total chromosomes but with the short arm of chromosome 5 missing (cri-du-chat syndrome). In Down syndrome, the person has an extra
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chromosome 21, which is abbreviated as 47XX21+ or 47XY21 +.
FIGURE 7.1 Photomicrographs of human chromosomes (karyotypes [photograph of chromosomes arranged in a standard classification]). If a blood sample is taken from a child or adult and the white blood cells are examined at the mitotic division phase of reproduction, transferred to slides, and photographed under high-power magnification, the individual chromosomes can be cut from the photograph and arranged according to size and shape. (A) Normal female karyotype. (B) Normal male karyotype.
Mendelian Inheritance: Dominant and Recessive Patterns
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 they are known as mendelian laws.
A person who has two like genes for a trait—for blue eyes, for example (one from the mother and one from the father)—on two like chromosomes is said to be homozygous for that trait. If the genes differ (a gene for blue eyes from the mother and a gene for brown eyes from the father, or vice versa), the person is said to be heterozygous for that trait. Many genes are dominant in their action over others; that is, when paired with other genes, dominant genes are always expressed in preference to the other genes. A gene that is not dominant is recessive. For example, brown eye color is dominant over blue, so a person with a heterozygous pattern would appear to have brown eyes. 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.
Mendelian laws permit the prediction of inheritance of traits, such as eye color, or the chance that a child born to parents with a certain genotype will be born with a disorder. Inheritance patterns for eye color or hair color provide a useful example of these principles. If the father is homozygous dominant (has two dominant genes for brown eye color) and the mother is homozygous recessive (has two genes for blue eye color), it can be predicted that their children have a 100% chance of being heterozygous for the trait (Fig. 7.2A); they will appear brown-eyed (the phenotype) but will carry a recessive gene for blue eyes (the genotype). If the father, however, is heterozygous (has one dominant gene and one recessive gene), a child born to this couple will have an equal chance of being brown-eyed or blue-eyed (Fig. 7.2B).
Suppose the mother is heterozygous instead of homozygous recessive and the father is homozygous dominant. When this pairing occurs, the chances are equal that their child will be homozygous dominant like the father or heterozygous like the mother. All the children's phenotypes will be brown eyes (Fig. 7.2C).
Suppose both parents are heterozygous. There is a 25% chance of their child's being homozygous recessive
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(appearing blue-eyed), a 50% chance of being heterozygous (appearing brown-eyed), and a 25% chance of being homozygous dominant (appearing brown-eyed). This is how two brown-eyed parents can produce a blue-eyed child (Fig. 7.2D), and it confirms that it is impossible to predict a person's genotype from the phenotype, or outward appearance.
FIGURE 7.2 Possible inheritance of eye color.
Checkpoint Question 1
Amy Alvarez is pregnant with her first child. Her phenotype refers to:
a. Her concept of herself as male or female.
b. Whether she has forty-six chromosomes or not.
c. Her actual genetic composition.
d. Her outward appearance.
View Answer
1. D. Phenotype is outward appearance; genotype is the actual chromosome makeup.
Inheritance of Disease
Since the entire human genome has been mapped, an increasing number of types of disease inheritance have been identified.
Autosomal Dominant Disorders
Although more than 3,000 autosomal dominant disorders are known, only a few are commonly seen. Most of them cause structural defects. With an autosomal dominant condition, either a person has two unhealthy genes (homozygous dominant) or is heterozygous, with the gene causing the disease stronger than the corresponding healthy recessive gene for the same trait. Huntington disease is a progressive neurologic disorder that usually manifests symptoms between 35 and 45 years of age and is characterized by loss of motor control and intellectual deterioration. It an example of a heterozygous inherited autosomal dominant disorder. It is now possible to detect people who will develop this disorder by analyzing for a specific gene on chromosome 4. Unfortunately, there is no cure for Huntington disease, so potentially affected individuals must make a difficult choice in deciding to undergo the analysis when there is nothing but palliative care for this ultimately fatal disorder (Dawson et al., 2004).
Other examples of autosomal dominantly inherited disorders include facioscapulohumeral muscular dystrophy (a disorder that results in muscle weakness), a form of osteogenesis imperfecta (a disorder in which bones are exceedingly brittle), and Marfan syndrome (a disorder of connective tissue in which the child is thinner and taller than normal and may have associated heart defects). If a person who is heterozygous for an autosomal dominant trait such as facioscapulohumeral muscular dystrophy mates with a person who is free of the trait, as shown in Figure 7.3A, the chances are even (50%) that a child born to the couple would have the disorder or would be disease- and carrier-free (i.e., carrying no affected gene for the disorder).
Two heterozygous people with a dominantly inherited disorder are unlikely to choose each other as reproductive partners. If they do, however, their chances of having children free from the disorder decline (Fig. 7.3B): there would be only a 25% chance of a child's being disease- and carrier-free, a 50% chance that the child would have
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the disorder as both parents do, and a 25% chance that a child would be homozygous dominant (i.e., have two dominant disorder genes), a condition that probably would be incompatible with life.
FIGURE 7.3 Autosomal dominant inheritance.
In assessing family genograms (maps of family relationships) for the incidence of inherited disorders, a number of common findings are usually discovered when a dominantly inherited pattern is present in the family:
  • One of the parents of a child with the disorder also will have the disorder (a vertical transmission picture).
  • The sex of the affected individual is unimportant in terms of inheritance.
  • There is usually a history of the disorder in other family members.
Figure 7.4 shows a typical genogram of a family with an autosomal dominantly inherited disorder.
Autosomal Recessive Inheritance
More than 1,500 autosomal recessive disorders have been identified. In contrast to structural disorders, these tend to be biochemical or enzymatic. Such diseases do not occur unless two genes for the disease are present (i.e., a homozygous recessive pattern). Many inborn errors of metabolism are recessively inherited in this way. Examples include cystic fibrosis, adrenogenital syndrome, albinism, Tay-Sachs disease, galactosemia, phenylketonuria, limb-girdle muscular dystrophy, and Rh-factor incompatibility.
An example of autosomal recessive inheritance is shown in Figure 7.5A. Both parents are disease-free of cystic fibrosis, but both are heterozygous in genotype, so they carry a recessive gene for cystic fibrosis. When this occurs, there is a 25% chance that a child born to them will be disease- and carrier-free (homozygous dominant for the healthy gene); a 50% chance that the child will be, like the parents, free of disease but carrying the unexpressed disease gene (heterozygous); and a 25% chance that the child will have the disease (homozygous recessive).
Suppose a woman with the heterozygous genotype shown in Figure 7.5A mates with a man who has no trait for cystic fibrosis. There is a 50% chance that a child born to them will be completely disorder- and carrier-free, like the father. Likewise, there is a 50% chance that their child will be heterozygous (i.e., a carrier), like the mother (see Fig. 7.5B). There is no chance in this case that any of their children will have the disorder. However, they should be aware that if a child of theirs who carries the trait eventually has children with a sexual partner who also has a recessive gene for the trait, the grandchildren may manifest the disease. Cystic fibrosis is caused by an errant gene on the seventh chromosome. As many as 1 in every 29 Caucasian people carries the trait. People who are concerned as to whether they have a recessive gene for the disorder can have a DNA analysis to reveal their status (Farrell & Farrell, 2003).
FIGURE 7.4 Family genogram: autosomal dominant inheritance.
FIGURE 7.5 Autosomal recessive inheritance.
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Twenty years ago, most children with cystic fibrosis died in early childhood and therefore never reached childbearing age. Today, with good management, such children can live to adulthood and have children of their own. If a person with cystic fibrosis (homozygous recessive) should choose a sexual partner without the trait, none of their children would have the disorder, but all would be carriers of a recessive gene for the disorder (see Fig. 7.5C).
If a person with cystic fibrosis mated with a person with an unexpressed gene for the disease, there would be a 50% chance that a child would have the disorder (homozygous) and a 50% chance that he or she would be heterozygous for the disorder (see Fig. 7.5D). If a person with the disorder mated with a person who also had the disorder, as shown in Figure 7.5E, there is a 100% chance that their child would have the disorder.
When family genograms are assessed for the incidence of inherited disease, situations commonly discovered when a recessively inherited disease is present in the family include the following:
  • Both parents of a child with the disorder are clinically free of the disorder.
  • The sex of the affected individual is unimportant in terms of inheritance.
  • The family history for the disorder is negative—that is, no one can identify anyone else who had it (a horizontal transmission pattern).
  • A known common ancestor between the parents sometimes exists. This explains how both male and female came to possess a like gene for the disorder.
Figure 7.6 shows a typical genogram of a family with an autosomal recessive inherited disorder.
X-Linked Dominant Inheritance
Some genes for disorders are located on, and therefore transmitted only by, the female sex chromosome (the X chromosome). There are about 300 known X-linked disorders, and their transmission is called X-linked inheritance. If the gene is dominant, only one X chromosome with the trait need be present for symptoms of the disorder to be manifested (Fig. 7.7A). Family characteristics seen with this type of inheritance include the following:
  • All individuals with the gene are affected.
  • All female children of affected men are affected; all male children of affected men are unaffected.
  • It appears in every generation.
  • All children of homozygous affected women are affected. Fifty percent of the children of heterozygous affected women are affected (Fig. 7.8).
FIGURE 7.6 Family genogram: autosomal recessive inheritance.
FIGURE 7.7 Sex-linked inheritance: (A) sex-linked dominant; (B, C) sex-linked recessive.
FIGURE 7.8 Family genogram: X-linked dominant inheritance.
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An example of a disease in this group is Alport's syndrome, a progressive kidney failure disorder.
X-Linked Recessive Inheritance
The majority of X-linked inherited disorders are recessive, and inheritance of the gene from both parents (homozygous recessive) is incompatible with life. Therefore, females who inherit the affected gene will be heterozygous, and, because a normal gene is also present, the expression of the disease will be blocked. On the other hand, because males have only one X chromosome, the disease will be manifested in any male children who receive the affected gene from their mother.
Hemophilia A, Christmas disease (a blood-factor deficiency), color blindness, Duchenne (pseudohypertrophic) muscular dystrophy, and fragile X syndrome are examples of this type of inheritance. Such a pattern is shown in Figure 7.7B, in which the mother has the affected gene on one of her X chromosomes and the father is disease-free. When this occurs, the chances are 50% that a male child will manifest the disease and 50% that a female child will carry the disease gene. 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. 7.7C).
When family genograms are assessed for inherited disorders, the following findings usually are apparent if an X-linked recessive inheritance disorder is present in the family:
  • Only males in the family will have the disorder.
  • A history of girls dying at birth for unknown reasons often exists (females who had the affected gene on both X chromosomes).
  • Sons of an affected man are unaffected.
  • The parents of affected children do not have the disorder.
Figure 7.9 shows a typical family genogram in which there is an X-linked recessive inheritance pattern.
Y-Linked Inheritance
Although genes responsible for features such as height and tooth size are found on the Y chromosome, no known disease genes are inherited by Y-chromosome transmission (Ward, 2003).
What if …
Amy Alvarez had a recessive X-linked chromosome disorder, such as hemophilia, and said that she wanted to have all boys because they would not show symptoms? Would she be well informed?
View Answer
1. X-linked recessive inherited illnesses are carried by the mother on an X chromosome, but the symptoms of these diseases are apparent in male offspring. Having only boys, therefore, would increase the chance a child would have the disease, not decrease it.
Multifactorial (Polygenic) Inheritance
Many childhood disorders such as heart disease, diabetes, pyloric stenosis, cleft lip and palate, neural tube disorders, hypertension, and mental illness tend to have a higher-than-usual incidence in some families. Diabetes is one example that has been studied closely. Certain human lymphocyte antigens (HLAs) inherited from both parents appear to play a role in genetic susceptibility to diabetes mellitus. Children who will develop diabetes mellitus can be shown to have an increased frequency of HLA B8, B15, DR3, and DR4 on chromosome 6. They lack DR2, an HLA that appears to be protective against diabetes mellitus.
FIGURE 7.9 Family genogram: X-linked recessive inheritance.
Diseases caused by multiple factors do not follow the mendelian laws of inheritance, probably because more than a single gene or HLA is involved. Environmental influences may be instrumental in determining whether the disorder is expressed. It may be difficult for parents to understand these disorders because their occurrence is so unpredictable. A family history, for instance, may reveal no set pattern. Some of these conditions have a predisposition to occur more frequently in one sex (e.g., cleft palate occurs more often in girls), but they can occur in either sex.
Mitochondrial Inheritance
Mitochondria are cell organelles that are found outside the cell nucleus. They are inherited solely from the cytoplasm of the ovum. Male carriers cannot pass a disorder carried in the mitochondria to any of their children. Females, on the other hand, will pass mitochondrial disorders to 100% of their children. A number of rare myopathies (muscle diseases) are inherited in this way. Mitochondria serve as markers for genetic testing (Speroff & Fritz, 2005).
Imprinting
Imprinting refers to the differential expression of genetic material and allows researchers to identify whether the chromosomal material has come from the male or female parent. In some instances, such as hydatidiform mole (see Chapter 15), it can be shown that no maternal contribution is made to a fertilized ovum. In Prader-Willi syndrome, a chromosome 15 abnormality in which children are severely obese and cognitively challenged, no paternal contribution is present at certain gene points (Goldstone, 2004).
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Chromosomal Abnormalities (Cytogenic Disorders)
In some instances of genetic disease, the abnormality occurs not because of dominant or recessive gene patterns but through a fault in the number or structure of chromosomes. When chromosomes are photographed and displayed, the result is termed a karyotype. Specific parts of chromosomes can be identified by karyotyping or by a process termed fluorescent in situ hybridization (FISH).
Nondisjunction Abnormalities
Meiosis is the type of cell division in which the number of chromosomes in the cell is reduced to the haploid (half) number for reproduction (i.e., 23 rather than 46 chromosomes). All sperm and ova undergo a meiosis cell division early in formation. During this division, half of the chromosomes are attracted to one pole of the cell and half to the other pole. The cell then divides cleanly, with 23 chromosomes in the first new cell and 23 chromosomes in the second new cell. Chromosomal abnormalities occur if the division is uneven (nondisjunction). The result may be that one new sperm cell or ovum has 24 chromosomes and the other has only 22 (Fig. 7.10). If a defective spermatozoon or ovum with 24 or 22 chromosomes fuses with a normal spermatozoon or ovum, the zygote (sperm and ovum combined) will have either 47 or 45 chromosomes, not the normal 46. The presence of 45 chromosomes does not appear to be compatible with life, and the embryo or fetus probably will be aborted. Down syndrome (trisomy 21) (47XX21+ or 47XY21+) is an example of a disease in which the individual has 47 chromosomes. There are three rather than two copies of chromosome 21 (Fig. 7.11).
The incidence of Down syndrome increases with increasing maternal age and is highest if the mother is older than 35 years of age and the father is older than 55. Thus, aging seems to present an obstacle to clean cell division. The incidence is 1:100 in women older than 40 years of age, compared with 1:1,500 in women younger than 20 years (Ward, 2003). Other examples of cell nondisjunction include trisomy 13 (Fig. 7.12) and trisomy 18 (cognitive challenged syndromes).
If nondisjunction occurs in the sex chromosomes, other types of abnormalities occur. Turner and Klinefelter syndromes are the most common types. In Turner syndrome (45XO), which is marked by webbed neck, short stature, sterility, and possibly cognitive challenge, the individual, although female, has only one X chromosome (or has two X chromosomes but one is defective). She appears to be female (female phenotype) because of the one X chromosome. In Klinefelter syndrome (marked by sterility and possibly cognitive challenge), the individual has male genitals but the sex chromosomal pattern is 47XXY.
Deletion Abnormalities
Deletion abnormalities are a form of chromosome disorder in which part of a chromosome breaks during cell division,
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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. For example, in cri-du-chat syndrome (46XY5q–), one portion of chromosome 5 is missing (see discussion later in this chapter).
FIGURE 7.10 Process of nondisjunction at the first and second meiotic divisions of the ovum and fertilization with normal sperm.
FIGURE 7.11 Karyotype of trisomy 21. (Courtesy of Dr. Kathleen Rao, Dept. of Ped., UNC.)
FIGURE 7.12 An infant with trisomy 13 has (A) a cleft palate and (B) supernumerary digits (polydactyly). (© NMSB/Custom Medical Stock Photo.)
Translocation Abnormalities
Translocation abnormalities are perplexing situations in which a child gains an additional chromosome through another route. A form of Down syndrome occurs as a translocation abnormality. 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. 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 (Pastva et al., 2004).
If, during meiosis, this abnormal chromosome 14 (carrying the extra 21 chromosome) 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 nondisjunction.
About 2% to 5% of children with Down syndrome have this type of chromosome pattern. It is important to identify parents who are translocation carriers, because their chance of having a child born with Down syndrome is higher than normal. If the father is the carrier, this risk is about 5%; if the mother is the carrier, the risk is about 15%. As many as 15% of couples who have frequent early spontaneous miscarriages may have this type of chromosomal aberration (Ward, 2003).
Mosaicism
Usually, a nondisjunction abnormality occurs during the meiosis stage of cell division, when sperm and ova halve their number of chromosomes. Mosaicism is an abnormal condition that is present when the nondisjunction disorder occurs after fertilization of the ovum, as the structure begins mitotic (daughter-cell) division. 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. Children with Down syndrome who have near-normal intelligence may have this type of pattern. 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+.
Isochromosomes
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. Some instances of Turner syndrome (45XO) may occur because of isochromosome formation.
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Checkpoint Question 2
Amy Alvarez is a balanced translocation carrier for Down syndrome. This term means that:
a. All of her children will be born with some aspects of Down syndrome.
b. All of her female and none of her male children will have Down syndrome.
c. She has a greater than average chance a child will have Down syndrome.
d. It's impossible for any of her children to be born with Down syndrome.
View Answer
2. C. Amy has a 21 chromosome attached to another chromosome, so with meiosis or cell division, there is a greater than usual chance a child will inherit an extra chromosome. It is not sex related.
Genetic Counseling
Anyone concerned about the possibility of transmitting a disease to his or her children should have access to genetic counseling for advice on the inheritance of disease. Such counseling can serve the following purposes:
  • Provide concrete, accurate information about inherited disorders
  • Reassure people who are concerned that their child may inherit a particular disorder that the disorder will not occur
  • Allow people who are affected by inherited disorders to make informed choices about future reproduction
  • Educate people about inherited disorders and the process of inheritance
  • Offer support by skilled health care professionals to people who are affected by genetic disorders
Genetic counseling may result in making individuals feel “well” or free of guilt for the first time in their lives. They may discover that the disorder they were worried about was not an inherited one but was rather a chance occurrence.
In other instances, counseling results in informing individuals that they are carriers of a trait that is responsible for a child's condition. Even when people understand that they have no control over this, knowledge about passing along a genetic disorder can cause guilt and self-blame. Marriages and relationships can suffer unless both partners are given adequate support.
It is essential that information revealed in genetic screening be kept confidential, because such information could be used to damage a person's reputation or harm a future career or relationship. This necessity to maintain confidentiality prevents health care providers from alerting other family members about the inherited characteristic unless the member requesting genetic assessment has given consent. In some instances, a genetic history reveals new information, such as that a child has been adopted or is the result of artificial insemination, or that a current husband is not the child's father. The member of the family seeking counseling has the right to decide whether this information may be shared with other family members.
The timing of genetic counseling is also important. The ideal time is before the first pregnancy. Some couples take this step before committing themselves to marriage, offering out of compassion for the partner not to involve him or her in a marriage commitment if children of the marriage would be subject to a serious inherited disorder. Other couples first become aware of a need for genetic counseling after the birth of a first child with a disorder. Couples who seek counseling after a first affected child is born need counseling before a second pregnancy occurs. They may not be ready for this, however, until the initial shock of their first child's condition and the grief reaction that may accompany it have run their course. Only then are they ready for information and decision making (Wallerstedt et al., 2003) (Box 7.2).
Even if a couple decides not to have any more children, it is important that they know that genetic counseling is available should their decision change. They also
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should be aware that as their children reach reproductive age, they too may benefit from genetic counseling. Couples who are most apt to benefit from a referral for genetic testing or counseling include the following:
  • A couple who has a child with a congenital disorder or an inborn error of metabolism. Many congenital disorders occur because of teratogenic invasion during pregnancy that has gone unrecognized. Learning that the abnormality occurred by chance rather than inheritance is important, because the couple will not have to spend the remainder of their childbearing years in fear that another child may be born with the disorder (although a chance circumstance could occur again). If a definite teratogenic agent, such as a drug the woman took during pregnancy, can be identified, the couple can be advised about preventing this occurrence in a future pregnancy.
  • A couple whose close relatives have a child with a genetic disorder, including a congenital disorder or inborn error of metabolism. It is difficult to predict the expected occurrence of “familial” or multifactorial disorders. Therefore, counseling should be aimed at educating the couple about the disorder, available treatment, and the prognosis or outcome. Based on this information, the couple can make an informed reproductive choice.
  • Any individual who is a known balanced translocation carrier. Understanding of his or her own chromosome structure and the process by which future children could be affected can help the individual make an informed choice about reproduction or can alert him or her to the importance of fetal karyotyping during any future pregnancy (Box 7.3).
  • Any individual who has an inborn error of metabolism or chromosomal disorder. Any person with a
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    disease should know the inheritance pattern of the disease and, like those who are balanced translocation carriers, should be aware of prenatal diagnosis, if possible, for his or her particular disorder.
  • A consanguineous (closely related) couple. The more closely related two people are, the more genes they have in common, so the more likely it is that a recessively inherited disease will be expressed. A brother and sister, for example, have about 50% of their genes in common; first cousins have about 12% of their genes in common.
  • Any woman older than 35 years of age and any man older than 45 years of age. This is directly related to the association between advanced parental age and the occurrence of Down syndrome.
  • Couples of ethnic backgrounds in which specific illnesses are known to occur. Mediterranean people, for example, have a high incidence of thalassemia, a blood disorder; those with a Chinese ancestry have a high incidence of another blood disorder, glucose-6-phosphate dehydrogenase (G6PD) deficiency (Box 7.4).
Nursing Responsibilities
Nurses play important roles in assessing for signs and symptoms of genetic disorders, in offering support to individuals who seek genetic counseling, and in helping with reproductive genetic testing procedures. Nurses can be instrumental in the following ways:
  • Alerting a couple to what procedures they can expect to undergo
  • Explaining how different genetic screening tests are done and when they are usually offered
  • Supporting a couple during the wait for test results
  • Assisting couples in values clarification, planning, and decision making based on test results
A great deal of time may need to be spent offering support for a grieving couple confronted with the reality of how tragically the laws of inheritance have affected their lives.
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However, genetic counseling is a role for nurses only if they are adequately prepared in the study of genetics. Without this background, genetic counseling can be dangerous and destructive.
Whether one is acting as a nursing member of a genetic counseling team or as a genetic counselor, some common principles apply. First, the individual or couple being counseled needs a clear understanding of the information provided. People may listen to the statistics of their situation (“Your child has a 25% chance of having this disease”) and construe a “25% chance” to mean that if they have one child with the disease, they can then have three normal children without any worry. A 25% chance, however, means that with each pregnancy there is a 25% chance that the child will have the disease (chance has no “memory” of what has already happened). It is as if the couple had four cards, all aces, with the ace of spades representing the disease. When a card is drawn from the set of four, the chance of its being the ace of spades is 1 in 4 (25%). When the couple is ready to have a second child, it is as if the card drawn during the first round is returned to the set, so the chance of drawing the ace of spades in the second draw is exactly the same as in the first draw. Similarly, the couple's chances of having a child with the disease remain 1 in 4 in each successive pregnancy.
Second, it is never appropriate for any health care provider to impose his or her own values or opinions on others. Individuals with known inherited diseases in their family must face difficult decisions, such as how much genetic testing to undergo or whether to terminate a pregnancy that will result in a child with a specific genetic disease. Couples need to be made aware of all the options available to them. Then they need to think about the options and make their own decisions. Couples always should understand that nobody is judging their decision, because they are the ones who must live with the decision (Box 7.5).
Checkpoint Question 3
Amy Alvarez was told at a genetic counseling session that she is a balanced translocation carrier for Down syndrome. What would be your best action regarding this information?
a. Be certain all of her family members understand what this means.
b. Discuss the cost of various abortion techniques with Amy.
c. Be sure Amy knows she should not have any more children.
d. Ask Amy if she has any questions that you could answer for her.
View Answer
3. D. Genetic counseling is confidential, so it can't be shared with family members indiscriminately. Health care providers shouldn't inject their own values into counseling.
Assessment for Genetic Disorders
Genetic counseling begins with careful assessment of the pattern of inheritance in the family. A history, physical examination of family members, and laboratory analysis, such as karyotyping (a visual presentation of chromosomes) or DNA analysis, are performed to define the extent of the problem and the chance of inheritance.
History
A detailed family history is obtained to determine whether any disorders are present in family members. The mother's age is important, because some disorders increase in incidence with age. Ethnic background also is important, because certain disorders occur more commonly in some ethnic groups than others. If the couple seeking counseling is unfamiliar with their family history, ask them to talk to senior family members about other relatives (grandparents, aunts, uncles) before they come for an interview. Ask specifically for instances of spontaneous miscarriage or children in the family who died at birth. In many instances, these children died of unknown chromosomal disorders or were miscarried because of one of the 70 or more known chromosomal disorders that are inconsistent with life.
An extensive prenatal history of any affected person should be obtained to determine whether environmental conditions could account for the condition. A family genogram is done (see Fig. 7.6) to attempt to diagnose the trend of inheritance. Such a diagram not only identifies
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the possibility of a chromosomal disorder occurring in a particular couple's children but also helps to identify other family members who might benefit from genetic counseling.
Taking a health history for a genetic genogram determination is often difficult because the facts detailed may evoke uncomfortable emotions such as sorrow, guilt, or inadequacy. Many people have only sketchy information about their families, such as, “The baby had some kind of nervous disease” or “Her heart didn't work right.” Attempt to obtain more information by asking the couple to describe the appearance or activities of the affected individual or asking for permission to obtain health records.
When a child is born dead, parents are advised to have a chromosomal analysis and autopsy performed on the infant. If at some future date they wish genetic counseling, this would allow their genetic counselor to have accurate medical information.
Physical Assessment
Because genetic disorders often occur in varying degrees of expression, a careful physical assessment of any family member with a disorder, that child's siblings, and the couple seeking counseling is needed. It is possible for an individual to have a minimal expression of a disorder that has gone undiagnosed. During inspection, pay particular attention to certain body areas, such as the space between the eyes; the height, contour, and shape of ears; and the number of fingers and toes and the presence of webbing. Dermatoglyphics (the study of surface markings of the skin) should also be done, noting any abnormal fingerprints or palmar creases, which appear with some disorders. Abnormal hair whorls or coloring can also be present.
Careful inspection of newborns is often sufficient to identify a child with a potential chromosomal disorder. Infants with multiple congenital anomalies, those born at less than 35 weeks' gestation, and those whose parents have had other children with chromosomal disorders need extremely close assessment. Table 7.1 lists the physical characteristics suggestive of some common inherited syndromes in children.
Diagnostic Testing
For genetic counseling to be effective, the exact type of genetic disorder must be identified accurately. Many diagnostic tests are available to provide important clues about possible disorders (Inga & Knutson, 2003). Before pregnancy, karyotyping of both parents and an already affected child provides a picture of the chromosome pattern that can be used to predict future children. Once a woman is pregnant, several other tests may be performed to help in the prenatal diagnosis of a genetic disorder. These include MSAFP analysis, CVS, amniocentesis, percutaneous umbilical blood sampling (PUBS), sonography, and fetoscopy.
Karyotyping
A karyotype is a visual presentation of the chromosome pattern of an individual. 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. They are then stained, placed under a microscope, and photographed. Chromosomes are identified according to size, shape, and stain; cut from the photograph, and arranged as in Figure 7.1. Any additional, lacking, or abnormal chromosomes can be visualized by this method.
TABLE 7.1 Common Physical Characteristics of Children With Chromosomal Syndromes
Characteristic Probable Syndrome
Late closure of fontanelles Down syndrome
Bossing (prominent forehead) Fragile X syndrome
Microcephaly Trisomy 18, trisomy 13
Low-set ears Trisomy 18, trisomy 13
Slant of eyes Down syndrome
Epicanthal fold Down syndrome
Abnormal iris color Down syndrome
Large tongue Down syndrome
Prominent jaw Fragile X syndrome
Low-set hairline Turner syndrome
Multiple hair whorls Trisomy 18, trisomy 13
Webbed neck Turner syndrome
Wide-set nipples Trisomy 13
Heart abnormalities Many syndromes
Large hands Fragile X syndrome
Clinodactyly Down syndrome
Overriding of fingers Trisomy 18
Rocker-bottom feet Trisomy 13
Abnormal dermatoglyphics Down syndrome
Simian crease on palm Down syndrome
Absence of secondary sex characteristics Klinefelter and Turner syndromes
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. New techniques also are available for identifying what cells to use for analysis. A few fetal cells circulate in the maternal bloodstream, most noticeably trophoblasts, lymphocytes, and granulocytes. They are present but few in number 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 the trisomies.
Maternal Serum Screening
Alpha-fetoprotein (AFP) is a glycoprotein produced by the fetal liver that reaches a peak in maternal serum between the 13th and 32nd week of pregnancy. The AFP level deviates from normal if a chromosomal or a spinal cord disorder is present. Most pregnant women have an MSAFP test done at the 15th week of pregnancy. If the result is abnormal, the amniotic fluid is then assessed. The level of AFP is elevated in spinal cord disease (more than twice the value of the mean for that gestational age) and is decreased in a chromosomal disorder such as trisomy 21. Unfortunately, the MSAFP test has a false-positive rate of about 30% if the date of conception is not well documented. Use of a “triple study” (AFP, estriol, and hCG) reduces this false-positive rate, although false-positive reports still occur (Fischbach, 2004).
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Analysis of a pregnancy-associated plasma protein A, which is also increased with a Down syndrome pregnancy, and measurement of the fetal neck thickness by sonogram are still other measures used for analysis if an MSAFP test is positive (Wapner et al., 2003). Women with an elevated serum result need confirmation by sonogram or amniocentesis and psychological support to face what may be a very grave finding in their infant. Receiving a false-positive report can be devastating to a family during the pregnancy, potentially interfering with bonding with the infant.
Chorionic Villi Sampling
CVS is a diagnostic technique that involves the retrieval and analysis of chorionic villi for chromosome or DNA analysis. Although this procedure may be done as early as week 5 of pregnancy, it is more commonly done at 8 to 10 weeks. With this technique, the chorion cells are located by ultrasound. A thin catheter is then inserted vaginally, or a biopsy needle is inserted abdominally or intravaginally, and a number of chorionic cells are removed for analysis (Fig. 7.13). CVS carries a small risk (less than 1%) of causing excessive bleeding, leading to pregnancy loss, and parents should be informed about this risk before the procedure is done. There also have been some instances of children being born with missing limbs after the procedure (limb reduction syndrome). This has occurred with a high enough frequency that women need to be well informed of the risk beforehand (Ward, 2003).
After CVS, the woman should be instructed to report chills or fever suggestive of infection or symptoms of threatened miscarriage (uterine contractions or vaginal bleeding). Women with an Rh-negative blood type need Rh immune globulin administration after the procedure to guard against isoimmunization in the fetus. The test is highly accurate and yields no more false-positive results than does amniocentesis.
FIGURE 7.13 Chorionic villi sampling. Since the villi arise from trophoblast cells, their chromosome structure is the same as in the fetus.
The cells removed in CVS are karyotyped or submitted for DNA analysis to reveal whether the fetus has a genetic disorder. Because chorionic villi cells are rapidly dividing, results are available quickly, perhaps as soon as the next day. If a twin or multiple pregnancy is present, with two or more separate placentas, cells are removed separately from each placenta. Because fraternal twins are derived from separate ova, one twin could have a chromosomal abnormality while the other does not.
Not all inherited diseases can be detected by CVS. Parents need to know that only those disorders involving abnormal chromosomes or nondisjunction, and those whose specific gene location is known, can be identified by CVS. The test does not reveal the extent of spinal cord abnormalities.
Table 7.2 shows common chromosomal disorders that can be diagnosed prenatally through karyotyping. Additional disorders that can be identified by DNA analysis are retinoblastoma, myotonic dystrophy, Huntington chorea, sickle cell anemia, thalassemia, and Duchenne muscular dystrophy (Ward, 2003). The decision to undergo CVS is a major one for a couple. As a rule, they are not making a decision simply for CVS. If the CVS reveals that their child is abnormal, they will be asked to make a decision about the future of the pregnancy.
Deciding to terminate a pregnancy is rarely easy. The couple may need a great deal of support with their decision, both to carry it through and to live with the decision afterward. If they decide not to terminate the pregnancy, they
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will need support during the remainder of the pregnancy and in the days after the birth. It may be difficult for a couple to believe that what the test showed is true. Only when they inspect the baby and see that the test was accurate—the child does have a genetic disorder—do they see the reality. The result may be long-lasting depression.
TABLE 7.2 Common Genetic Disorders That Can Be Detected by Amniocentesis or Chorionic Villus Sampling
Syndrome Chromosomal Characteristics Clinical Signs
Down syndrome Extra chromosome 21 Cognitively challenged
Protruding tongue
Epicanthal folds
Hypotonia
Translocation Down syndrome Translocation of a chromosome, perhaps 14/21 Same clinical signs as trisomy 21
Trisomy 18 Extra chromosome 18 Cognitively challenged
Congenital malformations
Trisomy 13 Extra chromosome 13 Cognitively challenged
Multiple congenital malformations
Eye agenesis
Cri-du-chat syndrome Deletion of short arm of chromosome 5 Cognitively challenged
Facial structure anomalies
Peculiar cat-like cry
Fragile X syndrome Distortion of the X chromosome Cognitively challenged
Philadelphia chromosome Deletion of one arm of chromosome 21 Chronic granulocytic leukemia
Turner syndrome Only one X chromosome present Short stature
Streak gonads
Infertility
Webbed neck
Klinefelter syndrome An extra X chromosome present (XXY) Small testes
Gynecomastia
Infertility
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 karyotyping of skin cells found in the fluid as well as an analysis of AFP or acetylcholinesterase. Assessing for acetylcholinesterase, a breakdown product of blood, helps to reduce false-positive results. If the acetylcholinesterase result is negative, it confirms that an elevated AFP level is not a false-positive reading caused by blood in the fluid. Some disorders, such as Tay-Sachs disease, can be identified by the lack of a specific enzyme, such as hexosaminidase A, in amniotic fluid. Because amniocentesis is also a common assessment for fetal maturity, it is discussed further in Chapter 8 (see also Fig. 8.14).
For the procedure, a pocket of amniotic fluid is located by sonography. Then a needle is inserted transabdominally, 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. 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. Women need support to wait for the procedure, to wait for test results, and to make a decision about the pregnancy. Women with an 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 limits.
Percutaneous Umbilical Blood Sampling
PUBS, or cordocentesis, is the removal of blood from the fetal umbilical cord at about 17 weeks using an amniocentesis technique (Fig. 7.14). This allows analysis of blood components as well as more rapid karyotyping than is possible when only skin cells are removed. PUBS is discussed further in Chapter 8.
Fetal Imaging
Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography are all diagnostic tools used to assess a fetus for general size and structural disorders of the internal organs, spine, and limbs. Because some genetic disorders are associated with physical appearance, sonography may be helpful. Sonography may be used concurrently with amniocentesis and causes no apparent risk to the fetus.
Fetoscopy
Fetoscopy is the insertion of a fiberoptic fetoscope through a small incision in the mother's abdomen
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into the uterus and membranes to visually inspect the fetus for gross abnormalities. It can be used to confirm a sonography finding, to remove skin cells for DNA analysis, or to perform surgery for a congenital disorder such as a stenosed urethra.
FIGURE 7.14 Percutaneous umbilical blood sampling. Blood is withdrawn from the cord using amniocentesis technique.
Preimplantation Diagnosis
It may be possible in the future for a fertilized ovum to be removed from the uterus by lavage before implantation and biopsied for DNA analysis. The ovum would then be reinserted or not, depending on the findings and the parents' wishes. This would provide genetic information extremely early in a pregnancy. The technique is currently possible with in vitro fertilization procedures used in fertility treatment. This technique may also allow healthy genes to be inserted to correct underlying disorders very early in pregnancy (therapeutic cloning or stem cell transfer) (Hochedlinger & Jaenisch, 2003).
Reproductive Alternatives
Some couples are reluctant to seek genetic counseling because they are afraid they will be told it would be unwise to have children. Helping them to realize that viable alternatives for having a family exist for them allows them to seek the help they need.
Artificial insemination by donor (AID) is an option for couples if the genetic disorder is one inherited by the male partner or is a recessively inherited disorder carried by both partners. AID is available in all major communities and can permit the couple to experience the satisfaction and enjoyment of a normal pregnancy.
If the inherited problem is one arising from the female partner, surrogate embryo transfer is an assisted reproductive technique that is a possibility. An oocyte donated by a friend or relative or provided by an anonymous donor is fertilized by the husband's sperm in the laboratory and then implanted into the woman's uterus (Brinsden, 2003). Like AID, donor embryo transfer offers the couple a chance to experience a normal pregnancy.
Use of a surrogate mother (a woman who agrees to be artificially inseminated, typically by the male partner's sperm, and bear a child for the couple) is still another possibility (Jadva et al., 2003). All of these procedures are expensive and, depending on individual circumstances, may have disappointing success rates. Assisted reproductive techniques are discussed in more detail in Chapter 6.
Adoption is an alternative many couples find rewarding (see Chapters 2 and 6). Also, choosing to remain child-free should not be discounted as a viable option. Many couples who have every reason to think they would have normal children choose this alternative because they believe their existence is full and rewarding without the presence of children.
Diagnosis of a disorder during pregnancy with prompt treatment at birth to minimize the prognosis and outcome of the disorder is another route to explore. Termination of a pregnancy that reveals a chromosomal or metabolic abnormality is a final option.
Couples need support from health care personnel to decide on an alternative that is correct for them, not one that they sense a counselor feels would be best. They may need to consider the ethical philosophy or beliefs of other family members when making their decision, although ultimately they must do what they believe is best for them as a couple. A useful place to start counseling might be with values clarification, to be certain the couple understands what is most important to them.
Future Possibilities
Stem cell research is looking at the possibility that immature cells from a healthy embryo (stem cells) could be implanted into an embryo with a known abnormal genetic makeup, replacing the abnormal cells or righting the affected child's genetic composition (Hochedlinger & Jaenisch, 2003). Stem cell research is costly, however, and produces some ethical questions (e.g., what will be the source of donor oocytes for the new technology?).
Legal and Ethical Aspects of Genetic Screening and Counseling
Nurses can be instrumental in seeing that couples who seek genetic counseling receive results in a timely manner and with compassion about what their results may mean
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to future childbearing. It is important to keep in mind several legal responsibilities of genetic testing, counseling, and therapy, including the following:
  • Participation by couples or individuals in genetic screening must be elective.
  • People desiring genetic screening must sign an informed consent for the procedure.
  • Results must be interpreted correctly yet provided to the individuals as quickly as possible.
  • The results must not be withheld from the individuals and must be given only to those persons directly involved.
  • After genetic counseling, persons must not be coerced to undergo procedures such as abortion or sterilization. Any procedure must be a free and individual decision.
Failure to heed these guidelines could result in charges of invasion of privacy, breach of confidentiality, or psychological injury caused by “labeling” someone or imparting unwarranted fear and worry about the significance of a disease or carrier state. All couples who seek counseling and are identified as being at risk for having a child with a genetic disorder must be informed of the risk and offered appropriate diagnostic procedures (e.g., amniocentesis). “Wrongful birth” lawsuits have been initiated against health care providers for not making this information available.
What if …
Amy Alvarez were pregnant with twins? One twin fetus is diagnosed as having Down syndrome, and the other is not. How would you counsel her if she wanted to abort the affected child, when the procedure also might endanger the child without the disorder?
View Answer
2. This is a true ethical question, so the answer depends on many factors. A major thing to consider would be the length of the pregnancy, as the risk to the second child increases with duration of pregnancy. Other values to weigh would be the value of this pregnancy to the parents, their personal beliefs about abortion, and their philosophy about raising a child who is cognitively challenged. Making certain this mother was aware of all her options would be important.
Common Chromosomal Disorders Resulting in Physical or Cognitive Developmental Disorders
A number of chromosomal disorders, particularly nondisjunction disorders, are easily detected at birth on physical examination. Many of these disorders leave children cognitively challenged. Care of the child who is cognitively challenged is discussed in Chapter 54.
Trisomy 13 Syndrome
In trisomy 13 syndrome (Patau syndrome), the child has an extra chromosome 13 and is severely cognitively challenged. The incidence of the syndrome is low, approximately 0.45 per 1,000 live births. Midline body disorders such as cleft lip and palate, heart defects, particularly ventricular septal defects, and abnormal genitalia are present. Other common findings include microcephaly with abnormalities of the forebrain and forehead; eyes that are smaller than normal (microphthalmos) or absent; and low-set ears. Most of these children do not survive beyond early childhood (see Fig. 7.12).
Trisomy 18 Syndrome
Children with trisomy 18 syndrome have three copies of chromosome 18. They are severely cognitively challenged. The incidence is approximately 0.23 per 1,000 live births. These children tend to be small for gestational age at birth and have markedly low-set ears, a small jaw, congenital heart defects, and usually misshapen fingers and toes (the index finger tends to deviate or cross over other fingers). Also, the soles of their feet are often rounded instead of flat (rocker-bottom feet). As in trisomy 13 syndrome, most of these children do not survive beyond early infancy (Ward, 2003).
Cri-du-Chat Syndrome
Cri-du-chat syndrome is the result of a missing portion of chromosome 5. In addition to an abnormal cry, which sounds much more like the sound of a cat than a human infant's cry, children with cri-du-chat syndrome tend to have a small head, wide-set eyes, and a downward slant to the palpebral fissure of the eye. They are severely cognitively challenged (Sarimski, 2003).
Turner Syndrome
The child with Turner syndrome (gonadal dysgenesis; 45XO) has only one functional X chromosome. The child is short in stature. The hairline at the nape of the neck is low-set, and the neck may appear to be webbed and short. A newborn may have appreciable edema of the hands and feet and a number of congenital anomalies, most frequently coarctation (stricture) of the aorta and kidney disorders. The child has only streak (small and nonfunctional) gonads, so that, with the exception of pubic hair, secondary sex characteristics do not develop at puberty. Lack of ovarian function results in sterility. The incidence is approximately 1 per 10,000 live births (Parker et al., 2003).
Although children with Turner syndrome may be severely cognitively challenged, difficulties in this area are more commonly limited to learning disabilities. Socioemotional adjustment problems may accompany the syndrome as well because of the lack of fertility and if the nuchal folds are prominent.
Human growth hormone administration may help children with Turner syndrome to achieve additional height (Cave et al., 2005). If treatment with estrogen is begun at approximately 13 years of age, secondary sex characteristics will appear, and osteoporosis may be prevented (Box 7.6). If females continue taking estrogen for three out of every four weeks, they will have withdrawal bleeding that results in a menstrual flow. This flow, however, does not correct the problem of sterility. Gonadal tissue is scant and inadequate for ovulation because of the basic chromosomal aberration.
Klinefelter Syndrome
Infants with Klinefelter syndrome are males with an XXY chromosome pattern (47XXY). Characteristics of the syndrome
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may not be noticeable at birth. At puberty, secondary sex characteristics do not develop; the child has small testes that produce ineffective sperm. Affected individuals tend to develop gynecomastia (increased breast size). The incidence is about 1 per 1,000 live births. Karyotyping can be used to reveal the additional X chromosome (Hall et al., 2003).
Fragile X Syndrome
Fragile X syndrome is an X-linked disorder in which one long arm of an X chromosome is defective. The incidence is about 1 in 1,000 live births. It is the most common cause of cognitive challenge in boys.
Before puberty, boys with fragile X syndrome typically may have maladaptive behaviors such as hyperactivity and autism. They are apt to have reduced intellectual functioning, with marked deficits in speech and arithmetic. They may be identified by the presence of a large head, a long face with a high forehead, a prominent lower jaw, and large protruding ears. Hyperextensive joints and cardiac disorders may also be present. After puberty, enlarged testicles may become evident. Affected individuals are fertile and can reproduce (Medved & Brockmeier, 2004).
Carrier females may show some evidence of the physical and cognitive characteristics. Although intellectual function from the syndrome cannot be improved, both folic acid and phenothiazine administration may improve symptoms of poor concentration and impulsivity.
Down Syndrome (Trisomy 21)
Trisomy 21, the most frequently occurring chromosomal abnormality, occurs in about 1 in 800 live births. It occurs most frequently in the pregnancies of women who are older than 35 years of age (the incidence is as high as 1 in 100 live births for these women). Paternal age (older than 55 years) may also contribute to the increased incidence in this age group.
The physical features of children with Down syndrome are so marked that fetal diagnosis is possible by sonography in utero. The nose is broad and flat. The eyelids have an extra fold of tissue at the inner canthus (an epicanthal fold), and the palpebral fissure (opening between the eyelids) tends to slant laterally upward. The iris of the eye may have white specks in it, called Brushfield spots. Even in the newborn, the tongue may protrude from the mouth because the oral cavity is smaller than normal. The back of the head is flat, the neck is short, and an extra pad of fat at the base of the head causes the skin to be so loose it can be lifted up (like a puppy's skin). The ears may be low-set. Muscle tone is poor, giving the baby a rag-doll appearance. This can be so lax that the child's toe can be touched against the nose (not possible in the average mature newborn). The fingers of many children with Down syndrome are short and thick, and the little finger is often curved inward. There may be a wide space between the first and second toes and between the first and second fingers. The palm of the hand shows a peculiar crease (a simian line), which is a single horizontal palm crease rather than the normal three creases in the palm (Fig. 7.15).
Children with Down syndrome usually are cognitively challenged to some degree. The challenge can range from that of an educable child (intelligence quotient [IQ] of 50 to 70) to one who is profoundly affected (IQ less than 20). The extent of the cognitive challenge is not evident at birth. Educable children may represent mosaic chromosomal patterns. The fact that the brain is not developing well is evidenced by a head size that is usually smaller than the 10th or 20th percentile at well-child visits.
These children also appear to have altered immune function and are prone to upper respiratory tract infections. Congenital heart disease, especially atrioventricular defects, is common. Stenosis or atresia of the duodenum, strabismus, and cataract disorders are also common. For unknown reasons, acute lymphocytic leukemia occurs approximately 20 times more frequently in children with Down syndrome than in the general population. Even if children are born without an accompanying disorder such as heart disease, their lifespan usually is only 50 to 60 years, because aging seems to occur faster than normal (Benke, 2004).
Children with Down syndrome need to be exposed to early educational and play opportunities (see Chapter 54).
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Because they are prone to infections, sensible precautions such as using good handwashing technique are important when caring for them. The enlarged tongue may interfere with swallowing and cause choking unless the child is fed slowly. As with all newborns, these infants need physical examination at birth to enable detection of the genetic disorder and initiation of parental counseling and support.
FIGURE 7.15 (A) Typical facial features of the child with Down syndrome. (© Barbara Proud.) (B) A simian line, a horizontal crease seen in children with Down syndrome. (SPL/Custom Medical Stock Photo.)
Checkpoint Question 4
Amy Alvarez's child is born with Down syndrome. What is a common physical feature of newborns with this disorder?
a. Spastic and stiff muscles
b. Loose skin at back of neck
c. A white lock of forehead hair
d. Wrinkles on the soles of the feet
View Answer
4. B. The loose skin at the back of the neck is so apparent it can be revealed by sonogram during pregnancy. Babies tend to be hypotonic, not hypertonic. Sole creases are an indication of any mature fetus.
Key Points
  • Genetic disorders are disorders resulting from a defect in the structure or number of genes or chromosomes. Genetics is the study of how and why such disorders occur.
  • A phenotype is a person's outward appearance. Genotype refers to the actual gene composition. A person's genome is the complete set of genes present. A karyotype is a graphic representation of the chromosomes that are present.
  • A person is homozygous if he or she has two like genes for a trait and heterozygous if he or she has two unlike genes for a trait.
  • Mendelian laws can predict the likely incidence of recessive or dominant diseases in offspring. Division disorders, including nondisjunction abnormalities, deletion, translocation, and mosaicism, also create genetic disorders.
  • Genetic counseling can be a role for nurses if they receive proper preparation and education. Assessment of genetic disorders consists of a health history, physical examination, and diagnostic studies such as CVS, amniocentesis, and MSAFP analysis.
  • Some karyotyping tests, such as CVS and amniocentesis, introduce a risk of spontaneous or threatened miscarriage. Be certain that women undergoing these tests remain in the health care facility for at least 30 minutes after the procedure to be sure that a complication such as vaginal bleeding, uterine cramping, or abnormal fetal heart rate is not present. Women with an Rh-negative blood type need Rh immune globulin administration after these procedures.
  • An important aspect of genetic counseling is respecting a couple's right to privacy. Be certain that information remains confidential and is not given indiscriminately to others, including other family members.
  • People who are told that a genetic abnormality does exist in their family may suffer a loss of self-esteem. Offering support to help them deal with
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    the feelings they experience is an important nursing intervention.
  • Common nondisjunction genetic disorders include Down syndrome (trisomy 21), trisomy 13, trisomy 18, Turner syndrome, and Klinefelter syndrome. Most of these syndromes include some degree of cognitive challenge.
Critical Thinking Exercises
  • Amy Alvarez, whom you met at the beginning of the chapter, doesn't know her family history so is unable to answer questions about family members. What questions would you want to ask about her husband's family? Suppose Mr. Alvarez tells you he had two brothers who died at birth. Would that finding be important?
  • Suppose Amy's husband's sister and her husband both carry a gene for a recessively inherited disorder, yet they have had five children and none of the children shows symptoms of the disorder. Is it possible for them to have had five children without any symptoms of the disease? What are the chances that their sixth child will also be disease-free?
  • Amy tells you, “My family will be so ashamed if a genetic defect happens in our family.” What does her statement tell you about her family's knowledge of genetic disorders?
  • Examine the National Health Goals related to genetic disorders. Most government-sponsored money for nursing research is allotted based on these goals. What would be a possible research topic to explore pertinent to these goals that would be applicable to the Alvarez family and also advance evidence-based practice?
References
Benke, P. J. (2004). Down syndrome. In Dambro, M. R. (Ed.), Griffith's 5-minute clinical consult. Philadelphia: Lippincott Williams & Wilkins.
Brinsden, P. R. (2003). Gestational surrogacy. Human Reproduction Update, 9 (5), 483–491.
Cave, C. B., Bryant, J., & Milne, R. (2005). Recombinant growth hormone in children and adolescents with Turner syndrome. Cochrane Library (Oxford) (2) (CD003887).
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Ward, K. (2003). Genetics and prenatal diagnosis. In Scott, J. R., et al. (Ed.), Danforth's obstetrics and gynecology (9th ed.). Philadelphia: Lippincott Williams & Wilkins.
Suggested Reading
Alfirevic, Z., Sundberg, K., & Brigham, S. (2005). Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Library (Oxford) (3) (CD003252).
Bates, B. R., et al. (2005). Warranted concerns, warranted outlooks: A focus group study of public understandings of genetic research. Social Science and Medicine, 60 (2), 331–344.
Beery, T. A., & Hern, M. J. (2004). Genetic practice, education, and research: An overview for advanced practice nurses. Clinical Nurse Specialist, 18 (3), 126–134.
Dinc, L. (2003). Ethical issues regarding human cloning: A nursing perspective. Nursing Ethics, 10 (3), 238–254.
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Donnenfeld, A. E., & Panke, E. S. (2004). What to do when your patient wants prenatal paternity testing. Contemporary OB/GYN, 49 (Special Issue), 44–50.
Horner, S. D. (2004). A genetics course for advanced clinical nursing practice. Clinical Nurse Specialist, 18 (4), 194–199.
Kornman, L., et al. (2005). Pre-conception and antenatal screening for the fragile site on the X-chromosome. Cochrane Library (Oxford) (1) (CD001806).
Lew-Starowicz, A., et al. (2003). Sexual aspects of women with Turner's syndrome. Sexuality and Disability, 21 (4), 241–248.
Pestka, E. L., & Brown, J. K. (2004). Genomics education for nurses in practice. Journal for Nurses in Staff Development, 20 (3), 145–149.
Read, C. Y., et al. (2004). Educational innovation: Promoting integration of genetics core competencies into entry-level nursing curricula. Journal of Nursing Education, 43 (8), 376–380.
Winkelman, C. (2004). Genomics: What every critical care nurse needs to know about the genetic contribution to critical illness. Critical Care Nurse, 24 (3), 34–45.
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