NR 283 Chapter 21 Congenital and Genetic Disorders

What is Polysomy X or Klinefelter syndrome ?

- A chromosomal Disorder - an extra X chromosome is present (XXY), resulting in a total of 47 chromosomes in each cell. Not all males show signs and are diagnosed, but typically, testes are small and sperm are not produced.

What is a genotype?

- Actual genetic information carried by the individual - All cells except the gametes of an individual have the same genotype. - Not all genes are expressed in all cells.

What are examples of Single Gene Disorders that are Autosomal- Dominant Disorders?

- Adult Polycystic Kidney Disease - Huntington chorea - Familial Hypercholesterolemia - Marfan Syndrome

What are Teratogenic agents?

- Agents that cause damage during embryonic or fetal development - They are often difficult to define. - Teratogenic agents may be present in the workplace - it is recommended that women avoid unnecessary exposure to drugs, chemicals, or radiation during the childbearing years.

What is X-Linked Recessive Disorder?

- Alleles for sex-linked recessive disorders are usually carried by the X chromosome. (The Y chromosome does not carry the same genes as does the X.) - The genes for X-linked disorders are recessive but are manifested in heterozygous males who lack the matching normal gene on the Y chromosome. - Females are carriers (without clinical signs) when they are heterozygous. - Carrier females have a 50% chance of producing an affected male child and an equal chance of producing a carrier female child in each pregnancy. - An affected male will transmit the defect to all his daughters, who become carriers, whereas his sons will neither be affected nor be carriers. (The male passes only the normal Y chromosome to his sons.) EXAMPLES: hemophilia A and Duchenne muscular dystrophy.

What are examples of Multi-factoral disorders?

- Anencephaly - Cleft lip and palate - Clubfoot - Congenital heart disease - Myelomeningocele - Schizophrenia

What genes are Single Gene Disorders?

- Autosomal- Dominant Disorders - Autosomal- Recessive Disorders - X- Linked Dominant Disorder - X- Linked Recessive Disorder

What are examples of Single Gene Disorders that are X-linked Recessive Disorders?

- Color Blindness - Duchenne Muscular Dystrophy - Hemophilia A

What are examples of Single Gene Disorders that are Autosomal- Recessive Disorders?

- Cystic Fibrosis - Phenylketonuria - Sickle cell Anemia - Tay- Sachs Disease

What are examples of chromosomal disorders?

- Down Syndrome - Monosomy X (Turner Syndrome) - Polysomy X (Klinefelter Syndrome) - Trisomy 18 (Edwards Syndrome)

Phenotype

- Expression of genes - Appearance of the individual's characteristics - (height, eye color, hair color)

What is gene therapy?

- Gene therapy involves the introduction of normal genes into living target cells, sometimes by means of a harmless virus or bacterium, thus changing the cell activity or replacing missing genes. - Gene therapy is a possible way to fix a genetic problem involving its source. - Gene therapy can be effective, particularly in humans, where a single gene appears to be responsible for a disease EXAMPLE: can be used for cystic fibrosis, polycystic kidney, or Huntington disease.

What is the enzyme effect? (AKA Storage disease or errors of metabolism)

- Happens with many recessive gene disorders - causes toxic metabolites to accumulate inside cells or in the blood and tissues, interfering with cell function and possibly causing death.

What is an Autosomal-Dominant Disorder

- In autosomal-dominant disorders, the presence of the defect in only one of the alleles produces a clinical expression of the disease. - An affected parent has a 50% probability to pass the disorder on to each child, regardless of the gender of the child - There are no carriers, and unaffected persons do not transmit the disorder. -Some of these conditions do not become evident clinically until midlife - Since it is dominant in the Punnett square the H marks if they have the disease (and they only need one for it to be present) - EXAMPLE: Huntington's Disease

What is Autosomal-Recessive Disorders

- In recessive disorders, both parents must pass on the defective gene to produce an affected (homozygous) child. - Male and female children are affected equally. - If the child is heterozygous (that is if one normal gene and one disease gene are present in the pair), then that child is a carrier and shows no clinical signs of disease. EXAMPLES: cystic fibrosis, sickle cell disease, phenylketonuria (PKU)

What is Monosomy X or Turner Syndrome?

- Is a chromosomal Disorder - occurs when only one sex chromosome, the X chromosome, is present. This person has only 45 chromosomes, resulting in a variety of physical abnormalities and lack of ovaries.

What is Trisomy 21 (Down Syndrome)?

- Is a chromosomal Disorder - resulting in numerous defects in physical and mental development. - in which there are three chromosomes rather than two in the 21 position; it is called trisomy 21 - Therefore an individual with Down syndrome has 47 chromosomes. - A less common form of Down syndrome exists in which part of chromosome 21 is attached to another chromosome (translocation).

What are developmental disorders?

- Is when there is an exposure to negative environmental influences during pregnancy and even before pregnancy such as radiation may cause changes in the sperm or ova. - The most critical time is the first 2 months of development, when the cells are dividing rapidly and differentiating, organogenesis is taking place, and the basic body structures are forming EXAMPLES: alcohol (fetal alcohol syndrome), cigarette smoking (low birth weight and increased risk of stillbirth), radiation, pharmaceuticals, cocaine abuse, and maternal infections. Chemicals such as mercury in food and water, as well as many drugs, can cross the placental barrier and damage the rapidly dividing cells of the embryo and fetus.

When can neonates be tested? How and why?

- Neonates can be tested approximately 48 hours after birth, using blood from a heel prick. - Most babies do not show signs of metabolic disorders at birth because the maternal kidney and liver have been active up to that time, but permanent damage to tissues can occur quickly thereafter. - Mandatory screening after birth is required in many areas for congenital metabolic disorders EXAMPLES: PKU, hypothyroidism, sickle cell anemia, maple syrup urine disease, galactosemia, congenital adrenal hyperplasia, biotinidase deficiency, and homocystinuria

Name the three types of genetic disorders?

- Single-gene disorders - Multi-factorial disorders - Chromosomal Disorders

What are Single-Gene Disorders

- Single-gene disorders are commonly classified by inheritance pattern, with the major groups being recessive, dominant, and X-linked recessive. - A single gene may control a limited function, such as color blindness, or it may have widespread effects, as in cystic fibrosis or Marfan syndrome

What are proteomics?

- Study of proteins that are elaborated when the gene is activated - It strives to characterize all of the proteins that are significant in the metabolic pathway for expression of a particular allele. - This is being funded to determine the shape and chemical activity of these crucial proteins so as to develop drugs specific to the metabolic pathway. AKA "designer drugs"

What are the characteristics of down syndrome?

- The head is small and has a flat facial profile. - The eyes are slanted, and their irises contain brush field spots - The mouth tends to hang open, revealing a large, protruding tongue and a high-arched palate. - The hands are small and have a single palmar (simian) crease. - The muscles tend to be hypotonic, the joints are loose, cervical abnormalities and instability are often evident, and stature is short. - Developmental stages are delayed. - Sexual development is often delayed or incomplete. - Many children have an assortment of other problems, including visual problems (cataracts, strabismus), hearing problems, obstructions in the digestive tract, celiac disease, congenital heart defects, decreased resistance to infection (immune deficit), and a high risk of developing leukemia.

What is an X-Linked Dominant Disorder

- The mutation responsible for fragile X syndrome is inherited as a dominant allele carried on the X chromosome; - thus males and females can be affected. - (females have a higher chance of getting it because they have 2 X's) - The mutation causes the affected X chromosome to appear constricted or broken. EXAMPLE: Fragile X syndrome (cause of mental retardation, learning disability, and learning disorders)

What is an incomplete dominant?

- When some genes do not wholly fit either the recessive or the dominant pattern. EXAMPLE: the gene for sickle cell disease is transmitted as a recessive, but may also be referred to as incomplete dominant because heterozygotes may display some clinical signs (sickle cell trait), whereas homozygotes show the full range of expression (sickle cell anemia)

What are single-gene disorders caused by?

- are caused by a change in one gene within the reproductive cells (ova or sperm); - this mutant gene is then transmitted to subsequent generations following the specific inheritance pattern for that gene. - Mutations in the body cells other than the reproductive cells may cause dysfunction but are not transmitted to offspring.

What are congenital anomalies?

- are disorders present at birth - They can include genetic or inherited disorders as well as developmental disorders

What are multifactorial disorders?

- are more complex - They may be polygenic or they may be the result of an inherited tendency toward a disorder that is expressed after exposure to certain environmental factors. - A combination of factors is required for the problem to be present, whether at birth or later in life. - Frequently the predisposing factors of a disorder include a familial tendency which means that family members have an increased risk of developing the disorder, but not every family member will have the disease EXAMPLE: cleft palate, congenital hip dislocation, congenital heart disease, type 2 diabetes mellitus, anencephaly, and hydrocephalus, Colon or breast cancer)

How can other congenital and developmental disorders happen?

- from premature birth, difficult labor and delivery, or exposure to a damaging agent during fetal development. - The defect may be limited to one organ, or it may affect the functions of many organs - Such congenital disorders often do not have a genetic component, but because they manifest at birth, they are termed congenital or developmental.

What are the benefits of DNA testing?

- gene testing was conducted on embryos (from in vitro fertilization) to ensure the birth of a child whose tissue was compatible with that of an older sibling ill with leukemia could then provide stem cells to the older sibling, saving the child's life. - Preimplantation genetic diagnosis through testing of embryos has also been used to guard against the birth of a child with a serious defect. - Another benefit of gene testing is seen in the identification of individuals who possess genes that place them at high risk of colon cancer

How do genetic disorders occur?

- is a disease that is caused by abnormalities in a person's DNA. - They may occur from a single-gene trait, a chromosomal defect, or they may be multi-factorial. - Clinical signs of genetic disorders are not always present at birth but may occur months or years later, for example, Huntington's disease, which is seen in adults. - Genetic disorders have social and psychological implications.

What is TORCH syndrome?

- is an acronym applied to routine prenatal screening tests for high-risk maternal infections Toxoplasmosis Other (hepatitis B, mumps, rubeola, varicella, gonorrhea, syphilis), Rubella Cytomegalovirus Herpes.

What is amniocentesis?

- or extraction of amniotic fluid from the uterus, and extraction of a sample of the chorionic villus of the fetus so as to examine a sample of fetal tissue. - Chromosomal abnormalities can then be detected by growing fetal cells, harvesting them, and then examining the chromosomes or karyotype - DNA tests, enzyme deficits, and the presence of abnormal constituents such as AFP can also be included in this examination.

What are some examples of invasive prenatal testing?

- ultrasonography - maternal blood tests such as the triple screen + quadruple screen - Amniocentesis - All these carry a slight risk to the fetus and mother. - One other drawback of prenatal diagnosis is that some tests may not show conclusive results for 4 to 6 weeks and are often not done until approximately 16 to 18 weeks into the pregnancy, leaving a long period of uncertainty.

What is a chromosomal Disorder (Anoamlie)

- usually result from an error during meiosis - This may be spontaneous or result from exposure to a damaging substance. - During meiosis, genes are often redistributed during the process of "crossover" in which chromosomes may swap portions. - There may be an error in chromosomal duplication or reassembly, resulting in the abnormal placement of part of the chromosome (a translocation), altered structure (deletion), or an abnormal number of chromosomes - CAN BE SEEN IN DOWN SYNDROME

What is a karytope?

- visual representation of chromosomes arranged in order of size - Used to diagnosis of chromosomal disorders

How many pairs of autosomes do we have?

22 pairs

How many pairs of chromosomes do humans have?

23 pairs of chromosomes

What are autosomes?

Any chromosome that is not a sex chromosome

What is Polygenic

Caused by multiple genes

Where is the genetic information of the cell stored?

Chromosomes

Why do we do DNA testing?

DNA testing for genetic disorders has been used to identify conditions in embryos and newborns.

What is an allele?

Different forms of a gene that are matched for a function (allele) at a specific location on the paired chromosome

What are examples of Single Gene Disorders that are X-linked Dominant Disorders?

Fragile-X Syndrome

What is a triple and quadruple screening?

Maternal blood test performed at 16 to 18 weeks. This test measures levels of alpha-fetoprotein (AFP), the beta subunit of human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) - Quadruple measures all of the above + inhibin A

When is testing recommended?

Testing is recommended for those who have a family history of a specific disease, those who have previously given birth to a child with an abnormality, and women more than 35 years of age.

What is the ultimate goal of genetic engineering?

The ultimate goal of gene manipulation is to remove a defective gene and supply a normal one so as to eliminate genetic defects.

why do we use diagnostic tests?

To detect some disease-causing genes or chromosomal abnormalities in carriers during the prenatal period, immediately after birth, or later in life when a disorder is suspected are available.

What does ultrasonography visualize?

can visualize structural anomalies

How many pairs of sex chromosomes do we have?

one pair (XX Female) (XY male)

What is gene penetration?

or frequency of expression of the gene among individuals carrying the gene.

What is genetic engineering, and what does it do?

refers to the laboratory practices of manipulating genes in living organisms, including microorganisms, plants and animals, and humans. - Genes may be altered by changing the sequence of DNA by rearrangement, deletion, or substitution