Question

gene defects, infectious agents, and congenital malformations are ____________ that can cause and contribute to the onset or severity of a child's illness?

a.biological determinants
b.social determinants
c.disease factors
d.dietary factors

Answer 1

Birth Defects

A birth defect is an anomaly that is congenital, or present from birth. Birth defects are the leading cause of infant mortality, causing 22 percent of all infant deaths. Approximately 3 to 4 percent of all live births are affected by a birth defect; the causes of most of them are unknown. Some birth defects are considered to be physical, while others are thought of as functional. Physical birth defects result in the malformation of a physical organ or limb, whereas functional birth defects are those that cause primarily functional, rather than physical, problems. Functional birth defects include mental retardation, congenital hearing loss, early-onset vision impairment, and numerous other health concerns. They may be caused by single gene mutations, or they may be due to polygenic or multifactorial inheritance.

Birth defects may be found in isolation or they may occur in combination in one child, as part of a larger syndrome. A syndrome is usually defined as the presence of three or more birth defects due to one underlying cause, that characterize a particular disease or condition. An example of this is Down syndrome.
Various Causes, Various Treatments

There are several etiologies of birth defects, including single gene mutations, polygenic and multifactorial conditions, chromosomal abnormalities, and teratogens, which cause growth or developmental abnormalities. These etiologies may cause both physical and functional birth defects. The diagnosis, treatment, and management of birth defects often involves a team of professionals and specialists. Among these specialists are clinical geneticists, medical geneticists, and genetic counselors. These are all genetic service providers who are trained to help make a diagnosis and identify whether a birth defect is isolated or part of a syndrome. An accurate diagnosis is of utmost importance in being able to treat the condition and anticipate any future health concerns that may arise.
LEADING CATEGORIES OF BIRTH DEFECTS
Birth Defects Estimated Incidence
Structural/Metabolic
Heart and circulation 1 in 115 births
Muscles and skeleton 1 in 130 births
Club foot 1 in 735 births
Cleft lip/palate 1 in 930 births
Genital and urinary tract 1 in 135 births
Nervous system and eye 1 in 235 births
Anencephaly 1 in 8,000 births
Spina bifida 1 in 2,000 births
Chromosomal syndromes 1 in 600 births
Down syndrome (Trisomy 21) 1 in 900 births
Respiratory tract 1 in 900 births
Metabolic disorders 1 in 3,500 births
PKU 1 in 12,000 births
Congenital Infections
Congenital syphilis 1 in 2,000 births
Congenital HIV infection 1 in 2,700 births
Congenital rubella syndrome 1 in 100,000 births
Other
Rh disease 1 in 1,400 births
Fetal alcohol syndrome 1 in 1,000 births
Single-Gene Mutations

Single-gene mutations are defects or changes in genes that may be passed on from generation to generation. The most common forms of inheritance include autosomal dominant, autosomal recessive, X-linked recessive, and new dominant mutations. Single-gene mutations may result in both structural and functional birth defects. These defects may be found in isolation or as part of a known syndrome and may display phenotypic variation, in which the same mutant gene leads to variable clinical problems. This often occurs with dominant mutations such as Marfan syndrome. A genetic disorder may also display reduced penetrance, wherein not everyone with the genetic mutation will have the disorder or trait. These are also known as "silent" disorders.
Autosomal Dominant Disorders

An example of an autosomal dominant disorder is achondroplasia, the most common form of short-limbed dwarfism in humans. Achondroplasia displays complete penetrance (everyone with the genetic defect also has the disorder), and it occurs in 1 out of 25,000 births. Most cases are sporadic rather than inherited.

Achondroplasia is a growth disorder caused by a mutation of the gene that encodes the fibroblast growth factor receptor 3 (FGFR3 ), and it is characterized by short limbs, malformed hands, a disproportionately large head, and abnormal facial features. Medical problems are due to abnormally configured bones and related structures, leading to hydrocephalus, problems of the spine, frequent sinus and ear infections, and orthopedic problems. If one parent is affected with achondroplasia, there is a 50 percent risk that an offspring will also be affected. If both parents are affected, there is a 25 percent chance that an offspring will inherit two gene copies and develop severe, life-threatening features. Two known mutations in FGFR3 account for 98 percent of all achondroplasia cases. This makes early identification, even prenatal diagnosis, relatively easy.

Another autosomal dominant condition is Marfan syndrome, which results from a defect in the synthesis, secretion, or utilization of the protein fibrillin, an important component of connective tissue throughout the body. The gene for Marfan syndrome is fibrillin 1 (FBR1 ). Marfan syndrome features are variable, including cardiovascular, skeletal, and ocular defects.

Marfan syndrome's most serious medical complication is the risk of sudden death from aortic dissection, a tear in the inner wall of the major artery leading from the heart. Approximately 75 percent of individuals with Marfan syndrome have a family history of the disease, with the rest occurring as new mutations. Because the syndrome is autosomally dominant, affected indviduals have a 50 percent risk of passing the mutated gene to their off-spring. The condition has full penetrance; therefore, all individuals who inherit this mutation will express some features of Marfan syndrome.
Functional Birth Defects

Fragile X syndrome is the most common cause of inherited mental retardation, occurring in one out of 1,000 births. It is caused by expansion of a "triplet repeat" section of nucleotides in the FMR-1 gene on the X chromosome. Triplet repeats are three-base-pair sequences in a gene that are abnormally repeated, sometimes dozens or even hundreds of times, causing abnormal protein sequence and structure. Because it is carried on the X chromosome, it affects males more often than females. In males, an FMR-1 gene with greater than 200 repeats is always associated with the syndrome. Inactivated FMR-1 gene causes impaired mental function. The FMR-1 protein is thought to help shape the connections between neurons that underlie learning and memory. Affected individuals may also have large testes, abnormal facial features, seizures, and emotional and behavior problems. DNA testing allows for detection of carriers as well as affected individuals, enabling the use of genetic counseling and prenatal testing.

Another common functional genetic disorder is hearing loss, which can result from a defect in any one of more than fifty different genes. One gene, connexin 26, may be responsible for a large portion of inherited hearing loss. Some forms of congenital hearing loss may be due to prenatal exposure to infectious agents such as rubella. Genetic screening or screening for hearing loss at birth may be the most important test for hearing impairment yet to be developed, as early recognition and treatment can lead to dramatic improvements in hearing and, consequently, in the development of language in early childhood.

Other genetic disorders that cause functional birth defects include those involved in various aspects of the immune system. The most severe form is severe combined immune deficiency (SCID), in which a major type of immune cell, the lymphocyte, is absent. People with SCID suffer life-threatening infections beginning in infancy and may require complete physical isolation. This was the case for David Vetter, who became known to the world as the "bubble boy."
Multifactorial and Polygenic Inheritance

Many traits and diseases are caused by the interaction of inherited genes and the environment. These are known as "multifactorial" traits. While all genes interact with the environment, the impact of the environment in multifactorial traits and diseases is usually greater than in single-gene traits and diseases. Prenatal environmental influences are inevitably filtered through the maternal-placental system and include factors such as infections, drugs, tobacco or alcohol use, diabetes, and industrial toxins.

Polygenic traits and diseases are due to the cumulative effect of multiple genes, working together. Many congenital birth defects are thought to be multifactorial, such as pyloric stenosis (narrowing of the passage from stomach to intestine), cleft lip and palate, clubfoot, and neural tube defects. When found as isolated birth defects, these conditions are thought to be explained by a "multifactorial threshold model."

The multifactorial threshold model assumes the gene defects for multifactorial traits are normally distributed within the population. This means that almost everyone has some genes involved with these conditions, with most individuals having too few of them to cause disease. Individuals will not become affected with the condition unless they have a genetic liability that is significant enough to push them past the threshold, moving them out of the unaffected range and into the affected range (Figure 1).
Examples of Multifactorial and Polygenic Effects

Cleft lip with or without cleft palate (CL/P) is a heterogeneous disorder (those children affected may have somewhat different abnormalities) occurring in 1 out of 1,000 births. Some CL/P cases occur as isolated birth defects, while others occur as part of a larger syndrome. The majority of CL/P cases are associated with multifactorial inheritance. The risk to relatives of affected individuals can be anywhere from 0.5 to 15 percent, depending on the severity of the clefting and the degree of relationship to the affected individual, with risks highest for first-degree relatives. Some unique cases of CL/P may be associated with genetic syndromes that are due to single-gene mutations or chromosomal abnormalities.

Clubfoot is another primarily multifactorial defect and occurs in 1 out of 10,000 Caucasian newborns. The estimated risk to relatives of inheriting this defect is between 2 to 20 percent, depending upon the family history. Clubfoot can also have genetic causes such as chromosomal abnormalities or single-gene disorders, or it may have an environmental origin, such as problems caused by amniotic fluid or structural abnormalities of the uterus that restrict fetal growth and mobility. Clubfoot can also be due to autosomal recessive as well as autosomal dominant inheritance, and it may also occur as part of a larger syndrome.

Another class of multifactorial disorders is known as neural tube defects (NTDs). The neural tube is the embryonic structure that develops into the brain and spinal cord. Failure of the neural tube to close, which normally occurs during in the fourth week of gestation, results in an NTD, usually spina bifida or anencephaly. Spina bifida ("open spine") is a defect of the spine. The most common form of spina bifida causes some degree of leg paralysis, impaired bladder and bowel control, and sometimes mental retardation. Anencephaly is a rapidly fatal condition in which a baby is born with a severely underdeveloped brain and skull.

While most NTDs are inherited as multifactorial disorders, a few result from single-gene disorders, chromosomal abnormalities, or teratogens. NTDs currently have an incidence of 1 per 2,000 births. This rate has fallen dramatically over the past thirty years, due to the remarkable effects of NTD-prevention efforts. Maternal deficiency in folate (a B vitamin) greatly increases the risk of NTDs, but taking multivitamins containing folic acid before conception and early in pregnancy is highly effective in preventing these disorders. High doses of folic acid are needed to help protect the fetuses of women with pregnancies previously affected by NTDs, and for those who need to take certain medications that interfere with folate metabolism .
Chromosome Disorders

Humans normally have twenty-two pairs of autosomes and two sex chromosomes, XX or XY, making forty-six chromosomes in total. Chromosomal abnormalities occur in about 0.5 percent of all live births and are usually due to an abnormal number of chromosomes. These are nearly always an addition or deletion of a single autosome or sex chromosome in a pair. One extra copy of a chromosome is called a trisomy, while one missing copy of a chromosome is called a monosomy. Sometimes only a segment of a chromosome is duplicated or lost.

Chromosomal disorders are diagnosed by karyotype analysis and can be done on adults by testing blood, skin, or other tissue. Karyotypes can also be performed on a fetus through specialized testing such as amniocentesis. Prenatal maternal blood tests are routinely used to screen for some trisomies, though accurate diagnosis requires fetal karyotyping.

Chromosomal abnormalities can occur in offspring of mothers of all ages, but the frequencies of these disorders increase with maternal age, rising exponentially after the maternal age of thirty-five. Advanced paternal age has far less impact. Chromosomal abnormalities can result in either physical or functional birth defects. The severity of these birth defects is highly variable and depends upon the exact chromosome problem.

Chromosomal defects include such problems as Down syndrome, Kline-felter's syndrome, and Turner's syndrome. The majority of Down syndrome cases are due to an extra chromosome 21. Trisomy 21 usually occurs as an isolated event within a family. It results in characteristic facial features, lax muscle tone, cardiac and intestinal anomalies, and mild or moderate mental retardation. Additional medical complications may also include recurrent ear and respiratory tract infections, vision problems, hearing difficulties, and short stature.

Klinefelter's syndrome is a sex chromosome abnormality that occurs in 1 of 600 males, with a karyotype of 47. Individuals with Klinefelter's syndrome possess an extra X chromosome: XXY. Clinical characteristics are variable and include some learning and developmental disabilities, hypogonadism , small testes, and gynecomastia occuring in puberty. The condition can be managed by administering testosterone supplements beginning in adolescence. As with some other sex chromosome abnormalities, adults with Klinefelter's syndrome are usually infertile.

Turner's syndrome is another sex chromosome disorder, with a karyotype of 45. In this condition, one X chromosome is missing. Turner's syndrome occurs in one out of 4,000 live births. Most females with Turner's syndrome are short and have webbing of the neck, a broad chest, and a lack of ovarian development, with a consequent lack of pubertal development and infertility. Female hormone therapy is often used to induce breast development and menstruation. The majority of conceptions resulting in a fetus with this condition end in a miscarriage, as Turner's syndrome is highly lethal in early fetal development.
Teratogen Exposure

A teratogen is any agent that can cause birth defects if a fetus is exposed to it. Teratogens are usually drugs or infectious agents such as bacteria or viruses, and can affect a fetus from as early as the first few weeks after conception through the second trimester. For this reason, ideally, women should avoid all medications during pregnancy. However, in some circumstances there are medical risks and benefits that must be weighed, particularly if a medication is important to the health of the prospective mother.

To properly assess the potential danger of a teratogen, information is required about its effect on embryonic development, its ease of passage across the placenta, and the dosage and timing of fetal exposure to the teratogen. There are, however, limitations on the ability of doctors to predict the risk of birth defects arising from fetal exposure to any particular drug because of the lack of information on the effects of multiple medication use and possible drug interactions, the inability to control for other exposures women may have during pregnancy, and the unique genetic susceptibilities of each person. In addition, there are limited clinical studies that address this problem.

Risks for birth defects or adverse pregnancy outcomes associated with any type of exposure are in addition to the 3 percent background risk for birth defects in all pregnancies. There is no evidence linking paternal exposures to teratogenicity for the developing fetus, though exposure to some agents can reduce male fertility.

One well-documented teratogen is the drug thalidomide, which was taken by tens of thousands of women in the 1950s and early 1960s to treat nausea during pregnancy, before its potent teratogenic effects were recognized. Even a single dose caused severe birth defects, including amelia (absence of limbs), phocomelia (short limbs), incomplete or absent bone growth, ear and eye abnormalities, congenital heart defects, and others.

Another potent teratogen is a substance called isotretinoin, marketed under the brand name of Accutane, used to treat severe acne. Birth defects following prenatal exposure include serious central nervous system defects such as hydrocephalus, microcephaly , and mental retardation, as well as cleft lip and palate and anomalies of cardiovascular, limb, eye, and other systems. For women who have taken this substance, it is recommended to delay pregnancy at least one month after they have stopped using it.

Like medications, "recreational" drugs such as alcohol and cocaine can act as teratogenic agents. Fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE) are the most common, completely preventable, and potentially devastating disorders caused by alcohol use during pregnancy. FAS is one of the leading causes of mental disabilities in children. Fetal exposure to alcohol creates additional problems in children born with FAS/FAE, such as characteristic facial features, growth retardation, central nervous system difficulties, learning disabilities, and behavioral problems. No amount of alcohol is thought to be safe during pregnancy; however, some of its effects may be prevented by stopping the exposure during or shortly after the first trimester.

Cocaine use during pregnancy is known to increase the risk of miscarriages and premature labor and delivery. Disturbances in the behavior of exposed newborns have been reported, such as irritability, irregular sleeping patterns, muscular rigidity, and poor feeding. Some birth defects associated with the use of this drug include urinary and genital malformations, as well as defects of the limbs, intestines, and the skull.

Conditions arising from infectious teratogenic agents include toxoplasmosis, syphilis, and rubella. In each of these cases, the mother is exposed to the infectious agent, then transmits it to the fetus. In toxoplasmosis, the parasite Toxoplasma gondii can be transmitted from cats to humans through contact with cat feces (cleaning litter box or gardening), or through consumption of undercooked meats, poorly washed fruits and vegetables, goat's milk, or raw eggs. Mother-to-fetus transmission is more likely if maternal infection occurs in the last few weeks before delivery, but early fetal exposure is generally associated with greater severity of defects in the child. Overall, 20 to 30 percent of untreated, infected newborns have birth defects, including seizures, microcephaly, and other severe effects on the nervous system. Treatment of the mother with antibiotics during pregnancy is safe for the fetus, and significantly reduces the likelihood of fetal infection.

Syphilis is an infection caused by the spirochete Treponema pallidum. This bacterium crosses the placenta and may result in fetal infection. If untreated, the pregnancy may end in miscarriage, stillbirth, or neonatal death. Signs of congenital infection include jaundice, joint swelling, rash, anemia, and characteristic defects of bone and teeth. Maternal treatment of this condition may help prevent the transmission to the fetus and its ill effects.

Rubella is the scientific name for the disease commonly known as German measles. Congenital rubella syndrome (CRS) results from the exposure of an unprotected pregnant woman to the rubella virus, and can lead to major birth defects, including serious malformations of the heart, blindness, deafness, and mental retardation. CRS has been virtually eradicated in the United States because of the near-universal vaccination against rubella, now part of the standard childhood immunizations program. Unfortunately, this vastly improved situation is not as common in much of the rest of the world.
Maternal Conditions

Birth defects can also result from physical conditions affecting the health of the mother. One common maternal condition associated with birth defects is diabetes mellitus, a multifactorial disorder. Mothers with diabetes have a two-to three-fold times greater risk of having a child with birth defects than the general population if their condition is not well controlled. However, good glucose control has been shown to correlate with a decreased risk of congenital malformations. Characteristic diabetic malformations include cardiovascular, craniofacial, genitourinary, gastrointestinal, and neurological abnormalities. The risk that the child born of a mother with diabetes mellitis will also develop diabetes as an adult is 1 to 3 percent.

Another maternal condition giving rise to birth defects is maternal phenylketonuria (PKU). This is an autosomal recessive disorder in which an enzyme called phenylalanine hydroxylase is defective. This enzyme normally converts a substance in the blood called phenylalanine to another substance called tyrosine. As a result, phenylalanine levels are high, resulting in mental retardation, microencephaly, growth retardation, cardiac problems, seizures, vomiting, and hyperactivity. Other traits associated with PKU are fair hair and skin and blue eyes. PKU can be effectively managed through changes in the diet, and women who have appropriately managed their diet can have pregnancies with healthy offspring.

Answer 2

hahhahaha jk I say C lol

Answer 3

Thanks

Answer 4

That was funny I was like, really, this isn't helping. but thanks for the answer

Answer 5

welcome