Chapter 7- Assessment Of Genetic Disorders In Obstetrics And Gynecology

Front 1

A ________ reveals the morphology and number of chromosomes

Back 1

Karyotype

Front 2

_________ mutations occur when one amino acid is substituted for another.
A) Insertion
B) Deletion
C) Missense
D) Nonsense

Back 2

C) Missense

Front 3

_______ mutations occur when premature stop codons are inserted into a sequence.
A) Insertion
B) Deletion
C) Missense
D) Nonsense

Back 3

D) Nonsense

Front 4

Prophase I is divided into five substages: leptotene, zygotene, pachytene, diplotene, and diakinesis. In prophase I the chromosomes condense and become shorter and thicker. Which of these stages marks the time when crossing over takes place, resulting in four distinct gametes?

Back 4

PACHYTENE

Front 5

What stage of Meiosis does the most genetic variation occur?

Which stage is the most error prone?

Back 5

ANAPHASE I (for both!)
In anaphase I the chromosomes go to opposite poles of the cell by independent assortment, signifying that there are 2 to the 23rd, or >8 million, possible variations. Anaphase I is also the most error-prone step in meiosis. The process of disjunction, where the chromosomes go to opposite poles of the cell, can result in nondisjunction, where both chromosomes go instead to the same pole. Nondisjunction is a common cause of chromosomally abnormal fetuses.

Front 6

How does Meiosis II differ from Mitosis?

Back 6

The second meiotic division (meiosis II) is similar to mitosis, except that the process occurs within a cell with a haploid number of chromosomes.

Front 7

What is the result of Meiosis II?

Back 7

The result of meiosis II is 4 haploid daughter cells

Front 8

What is Heteroploidy?

What are the forms in which it occurs?

Back 8

Heteroploidy: Any alteration in chromosome number.
2 forms: Euploidy & Aneuploidy

Front 9

Choose Euploidy or Aneuploidy

The haploid number of 23 chomosomes is altered.

Back 9

Euploidy
An example of euploidy is triploidy, in which the haploid number has been multiplied by 3. The karyotype is 69,XXX or 69,XXY.

Front 10

What are the 2 possible mechanisms by which triploidy can occur?

Back 10

Triploidy results from double fertilization of a normal haploid egg or from fertilization by a diploid sperm. Such abnormalities usually result in conceptions of *partial hydatidiform moles* and end spontaneously in the first trimester.

Front 11

What is Aneuploidy?

Back 11

In aneuploidy, the DIPLOID number of 46 chromosomes is altered.

Recall that in Euploidy, the HAPLOID number is changed

Front 12

Are the trisomies (21, 18, 13, & 16) considered Euploidies or Aneuploidies?

Back 12

The trisomies are ANEUPLOIDIES in which there are three copies of an autosome instead of two.

Front 13

Trisomy 21 causes______ ____
Trisomy 18 causes ____ _____
Trisomy 13 causes _____ _____

Back 13

21- Down syndrome
18- Edward Syndrome
13- Patau Syndrome

Most trisomies result from maternal meiotic nondisjunction, a phenomenon that occurs more frequently as a woman ages

Front 14

_______ is the term used to describe the presence of 2 or more cell populations with different karyotypes.

Back 14

Mosaicism

Front 15

What are the 5 most common sex chromosome abnormalities?

Back 15

The most common are
45,X
47,XXY
47,XXX
47,XYY
Mosaicism

Front 16

Which type of chromosomal Abnormality is more common:
Numerical or Structural?

Back 16

NUMERICAL

Front 17

A _______ occurs when a portion of a chromosome segment is lost

Back 17

DELETION

Front 18

What is a TERMINAL DELETION?

Back 18

Occurs when the missing portion of the chromosome is appended to the end of the long or short arm

Front 19

What happens when the missing portion of the chromosome is appended to both the long arm and the short arm of the same chromosome?

Back 19

A RING CHROMOSOME can result.

Front 20

What is an Interstitial Deletion?

Back 20

An interstitial deletion occurs when the deleted portion lacks a centromere, or in cases involving chromosomal breakage

Front 21

________ occur when the portion of an interstitially deleted segment is inserted into a nonhomologous chromosome.

Back 21

Insertions

Front 22

Which Trisomy is described by the following:
Moderate to severe mental retardation; characteristic facies; cardiac abnormalities; increased incidence of respiratory infections and leukemia; only 2% live beyond 50 years

Back 22

TRISOMY 21: DOWN SYNDROME

Front 23

Which Trisomy is described by the following:
Severe mental retardation; multiple organic abnormalities; less than 10% survive 1 year

Back 23

Trisomy 18 (Edwards syndrome)

Front 24

Which trisomy is described by the following:
Severe mental retardation; neurologic, ophthalmologic, and organic abnormalities; 5% survive 3 years

Back 24

Trisomy 13 (Patau syndrome)

Front 25

Which trisomy is described by the following:
Lethal anomaly occurs frequently in first-trimester spontaneous abortions; no infants are known to have this trisomy.

Back 25

Trisomy 16

Front 26

Which Chromosomal Abnormality is described by the following:
45 X karyotype, Occurs frequently in first-trimester spontaneous abortions; associated primarily with unique somatic features; patients are not mentally retarded, although IQs of affected individuals are lower than those of siblings

Back 26

45, X
Turner syndrome

Front 27

47 XXY= ___________

What are the somatic abnormalities associated with this?

Back 27

Klinefelter Syndrome

Characterized by a tall, eunuchoid habitus and small testes;

Front 28

What are the somatic abnormalities associated with 47XXX and 47XYY?

Back 28

Individuals do not usually exhibit somatic abnormalities, but 47,XYY individuals may be tall

Front 29

NAME THE CHROMOSOMAL ABNORMALITY:
Severe mental retardation, microcephaly, distinctive facial features, characteristic “cat's cry” sound (cri du chat syndrome)

Back 29

del(5p)

RARE

Front 30

What type of abnormality in chromosome *structure* causes Duchenne muscular dystrophy?

A) Deletion
B) Insertion
C) Inversion
D) Robertsonian Translocation
E) Reciprocal Translocation

Back 30

A) Deletion

Loss of a chromosome segment resulting in imbalance

Front 31

________ occur when the portion of an interstitially deleted segment is inserted into a nonhomologous chromosome.

Back 31

Insertions

Front 32

Which Trisomy is described by the following:
Moderate to severe mental retardation; characteristic facies; cardiac abnormalities; increased incidence of respiratory infections and leukemia; only 2% live beyond 50 years

Back 32

TRISOMY 21: DOWN SYNDROME

Front 33

Which Trisomy is described by the following:
Severe mental retardation; multiple organic abnormalities; less than 10% survive 1 year

Back 33

Trisomy 18 (Edwards syndrome)

Front 34

Which trisomy is described by the following:
Severe mental retardation; neurologic, ophthalmologic, and organic abnormalities; 5% survive 3 years

Back 34

Trisomy 13 (Patau syndrome)

Front 35

Which trisomy is described by the following:
Lethal anomaly occurs frequently in first-trimester spontaneous abortions; no infants are known to have this trisomy.

Back 35

Trisomy 16

Front 36

Which Chromosomal Abnormality is described by the following:
45 X karyotype, Occurs frequently in first-trimester spontaneous abortions; associated primarily with unique somatic features; patients are not mentally retarded, although IQs of affected individuals are lower than those of siblings

Back 36

45, X
Turner syndrome

Front 37

47 XXY= ___________

What are the somatic abnormalities associated with this?

Back 37

Klinefelter Syndrome

Characterized by a tall, eunuchoid habitus and small testes;

Front 38

What are the somatic abnormalities associated with 47XXX and 47XYY?

Back 38

Individuals do not usually exhibit somatic abnormalities, but 47,XYY individuals may be tall

Front 39

NAME THE CHROMOSOMAL ABNORMALITY:
Severe mental retardation, microcephaly, distinctive facial features, characteristic “cat's cry” sound (cri du chat syndrome)

Back 39

del(5p)

RARE

Front 40

What type of abnormality in chromosome *structure* causes Duchenne muscular dystrophy?

A) Deletion
B) Insertion
C) Inversion
D) Robertsonian Translocation
E) Reciprocal Translocation

Back 40

A) Deletion

Loss of a chromosome segment resulting in imbalance

Front 41

What type of Abnormality in chromosome structure causes Hemophilia A?

A) Deletion
B) Insertion
C) Inversion
D) Robertsonian Translocation
E) Reciprocal Translocation

Back 41

B) Insertion

A segment removed from one chromosome is inserted into another

Front 42

What type of Abnormality in chromosome structure causes Inv(9), the most common of it's sort?

A) Deletion
B) Insertion
C) Inversion
D) Robertsonian Translocation
E) Reciprocal Translocation

Back 42

C) Inversion (note: no clinical sequelae for this one)

A single chromosome has two breaks with reattachment in an inverted fashion

Front 43

What type of Abnormality in chromosome structure is thought to be linked to Down Syndrome?

A) Deletion
B) Insertion
C) Inversion
D) Robertsonian Translocation
E) Reciprocal Translocation

Back 43

D) Robertsonian Translocation

Loss of the short arm of two acrocentric chromosomes; the acrocentric chromosomes are 13, 14, 15, 21, and 22

t(14q21q); one of the possible causes of Down syndrome

Front 44

What type of Abnormality in chromosome structure is described by Breakage of nonhomologous chromosomes with a reciprocal exchange?

A) Deletion
B) Insertion
C) Inversion
D) Robertsonian Translocation
E) Reciprocal Translocation

Back 44

Reciprocal translocation

Common (1 in 600 newborns); usually harmless

Front 45

An inversion is the result of faulty repair of a chromosomal breakage. The broken portion is inserted into the chromosome in an inverted fashion. A ________ inversion occurs when both breaks occur on one arm of a chromosome. These types of inversions do not include the centromere, the region where the chromosome pairs are joined.

Back 45

Paracentric Inversion

Paracentric inversions cannot be identified by a traditional karyotype because the arms appear to be of normal length.

Front 46

A translocation involves the transfer of two chromosome segments, usually between nonhomologous (nonpaired) chromosomes. They are the most common form of structural rearrangements in humans. A translocation is described as _________ when equal amounts of genetic material are exchanged between chromosomes, and _________ when the chromosomes receive unequal amounts of genetic material. Two types of translocations are possible.

Back 46

1. Balanced
2. Unbalanced

Front 47

Robertsonian Translocations only occur in which type of chromosome?

Back 47

A Robertsonian translocation only occurs in *AROCENTRIC* chromosomes—those in which the centromere is located very near one end (chromosomes 13, 14, 15, 21, and 22).

A person with a Robertsonian translocation is phenotypically normal, but the gametes they produce may be unbalanced.

Front 48

What are the most clinically important Robertsonian Translocations?

Back 48

Those involving chromosome 21 and another acrocentric chromosome, most commonly chromosome 14.

21q14!!!!

Front 49

What is a balanced Reciprocal Translocation?

Back 49

Balanced reciprocal translocations may involve any chromosome and are the result of a reciprocal exchange of chromosome material between two or more chromosomes. Like those with Robertsonian translocations, individuals with a balanced reciprocal translocation are also phenotypically normal but may produce gametes with unbalanced chromosomes. The observed risk for a chromosomal abnormality in an offspring is less than the theoretical risk, because some of these gametes result in nonviable conceptions. In general, carriers of chromosome translocations identified after the birth of an abnormal child have a 5% to 30% risk of having unbalanced offspring. Children with an unbalanced chromosome translocation are at increased risk for mental retardation, neurodevelopmental delay, and other congenital abnormalities.

Front 50

Marfan syndrome, achondroplasia, and Huntington disease are all examples of genetic disorders with which type of inheritance pattern?

Back 50

AUTOSOMAL DOMINANT

Front 51

Which type of inheritance pattern is described below:

Gene expression rarely skips a generation.
An affected individual will transmit the gene to progeny 50% of the time.
There should be equal sex distribution among affected relatives; males should be able to transmit to males and females to females.
An unaffected first-degree relative will not transmit the gene to his or her progeny.

Back 51

Characteristics of Autosomal Dominant Disorders

Front 52

Which type of inheritance pattern is described below:

Gene expression may appear to skip generations.
Both males and females are affected.
Neither parent is usually affected; affected individuals usually do not have affected children.
If one parent is a carrier, half of the offspring will be carriers of the gene. If both parents are carriers, the risk of transmission of the disorder is 25%.
If the suspected disorder is noted to be rare, consanguinity should be suspected.

Back 52

Characteristics of Autosomal Recessive Disorders

Front 53

Which type of inheritance pattern is described below:

More common in males than in females
An affected male will not pass the disease to his son, but all the daughters will be carriers
The disease is transmitted from carrier females to affected males.

Back 53

X-Linked Recessive Disease

Front 54

Which type of inheritance pattern is described below:

The disease is usually twice as likely in females than in males.
An affected male will transmit the disease to all of his daughters, but not to any of his sons.
Heterozygous females will transmit the gene to 50% of their offspring, whereas homozygous females will transmit the gene to all of their offspring.

Back 54

X-Linked Dominant Disease

Front 55

Phenotypic expression of autosomal dominant genes is not always straightforward and may vary depending on specific characteristics of the gene. For example, some individuals with neurofibromatosis have only a few café au lait spots, whereas others have large tumors. What is the name of this phenomenon?

Back 55

VARIABLE EXPRESSION

Variable expressivity is the varying expression of a disease in an affected person.

Front 56

___________describes the likelihood that a person carrying the gene will be affected

Back 56

PENETRANCE

Neurofibromatosis demonstrates 100% penetrance (although it has varying expression!).

Retinoblastoma is an example of incomplete penetrance; not all affected individuals will express any obvious form of disease.

Front 57

_________refers to an increase in severity and earlier expression of disease with each subsequent generation.

What is an example of a genetic mutation that shows this phenpomenon?

Back 57

ANTICIPATION

An example of a genetic mutation that shows anticipation is Huntington disease, where an expansion of the trinucleotide repeat, GAG, leads to earlier expression of the disease in affected offspring.

Front 58

Sickle cell disease, Tay Sachs, PKU and Cyctic Fibrosis are examples of what type of inheritance pattern?

Back 58

AUTOSOMAL RECESSIVE

During pregnancy, unless a woman has been screened for a particular disease based on her risk factors, carriers of a recessive gene will not know they are carriers until they have affected offspring.

Front 59

T/F:

X-linked recessive diseases are much more common than X-linked dominant diseases

Back 59

TRUE

Front 60

X- linked recessive or dominant?

1) HEMOPHILIA
2) COLORBLINDNESS
3) HYPOPHOSPHATEMIA

Back 60

1) HEMOPHILIA: X-linked recessive
2) COLOR BLINDNESS: X-linked recessive
3) HYPOPHOSPHATEMIA: X-linked dominant

Front 61

Which X-Linked disorder causes mental retardation, is caused by a repeat in the CGG sequence in a specific gene on the X-Chromosome?

Back 61

Fragile X syndrome

Transmission of the disease-producing genetic mutation to a fetus depends on the sex of the parent and the number of repeats in the parental gene. If the number of repeats is between 61 and 200, the individual is said to have a “premutation.” These individuals are phenotypically
normal, although women carrying the premutation are at increased risk for premature ovarian failure. A full mutation is characterized by more than 200 repeats. These individuals display the signs and symptoms of the disorder.

Front 62

What is Multifactorial Inheritance?

What are some examples of multifactorial traits?

Back 62

Multifactorial disorders are caused by a combination of factors, some genetic and some nongenetic (i.e., environmental). Multifactorial disorders recur in families, but are not transmitted in any distinctive pattern.

Examples: Cleft lip, with or without cleft palate; congenital cardiac defects; neural tube defects; and hydrocephalus.

Front 63

What the first step in assessing risk factors for genetic disorders?

Back 63

Document information about the patient's family and personal *history*....bet you didn't see that one coming!

Front 64

What is the mainstay of surveillance for infectious and teratogen-induced congenital abnormalities?

Back 64

Ultrasonography is the mainstay of surveillance for infectious and teratogen-induced congenital abnormalities.

Because these defects are not gene-based, family history and genetic testing procedures, such as amniocentesis or CVS, cannot be used to detect these abnormalities.

Front 65

The incidence of trisomy 21 (Down syndrome) among newborns of 35-year-old women is 1:385.

True or Flase: Although the risk increases with age, the majority of cases of Down syndrome occur in women younger than 35 years of age.

Back 65

TRUE!

Front 66

True or false:

Women who have had a previous pregnancy complicated by trisomy 21, 18, or 13 or any other trisomy in which the fetus survived at least to the second trimester, are at risk of having another pregnancy complicated by the same or different trisomy.

Back 66

TRUE!

The risk of trisomy recurrence is 1.6 to 8.2 times the maternal age risk, depending on several factors

Front 67

True or False:

At least half of all first-trimester pregnancy losses result from fetal chromosomal abnormalities.

Back 67

True!

The most common are monosomy X; polyploidy (triploidy or tetraploidy); and trisomies 13, 16, 18, 21, and 22

Front 68

Does increased Paternal Age (particularly after age 50) predispose the fetus to an increase in gene mutations, like advanced maternal age does?

Back 68

Yes.

They are gene mutations that can affect X-linked recessive and autosomal dominant disorders, such as neurofibromatosis, achondroplasia, Apert syndrome, and Marfan syndrome.

Front 69

Tay-Sachs, Gaucher, and Niemann-Pick diseases occur with greater frequency in individuals of what descent?

Back 69

Ashkenazi Jewish

Front 70

What ethnic group is at increased risk of cystic fibrosis, with an estimated carrier percentage of 1 in 22?

Back 70

Caucasians of Northern European descent

Front 71

β-thalassemia is found at increased frequency in individuals of _______ origin and α-thalassemia in individuals of _______ origin.

Back 71

Beta- Mediterranean

Alpha- Asian

Front 72

What is the purpose of prenatal genetic screening?

Back 72

The purpose of prenatal genetic screening is to define the risk for a genetic disease in a low-risk population.

Front 73

What is the difference between a Screening test and a Diagnostic test?

Back 73

A screening test differs from a diagnostic test in that screening tests only assess the risk that a child will have a genetic disease; they cannot confirm or rule out the presence of the disease. A diagnostic test is given if a screening test is positive, to assess whether the disease is present or absent in the developing fetus.

Genetic screening tests are routinely offered to all women to detect neural tube defects (NTDs), Down syndrome, and trisomy 18. In addition, individuals of certain ethnic groups can be tested to detect whether they carry a gene for a particular disorder.

Front 74

1st trimester screening tests used to assess the risk of what 3 abnormalities in the developing fetus?

Back 74

Down syndrome, trisomy 18, and trisomy 13

Front 75

First-semester serum screening for Down syndrome consists of tests for levels of WHAT two biochemical markers?

Back 75

Free or total human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A).

Front 76

What hCG and PAPP-A findings have been associated with Down Syndrome?

Back 76

An elevated level of hCG and a decreased level of PAPP-A have been associated with Down syndrome.

Front 77

What is an U/S marker for Down Syndrome?

Back 77

*Size of the nuchal transparency (NT)* a fluid collection at the back of the fetal neck that can be seen between 10 and 14 weeks of gestation.

An increase in the size of the NT between 10 4/7 and 13 6/7 weeks of gestation is recognized to be an early presenting feature of a variety of chromosomal, genetic, and structural abnormalities. When used alone, NT measurement has a detection rate for Down syndrome of 64% to 70%.

Front 78

True or False:
Women found to have increased risk with first-trimester screening tests should be offered genetic counseling and the option of invasive fetal testing CVS in the first trimester or amniocentesis in the second trimester.

Back 78

TRUE

An advantage of first-trimester screening is that the tests are performed early enough so that decisions can be made regarding continuing the pregnancy, if necessary

Front 79

What Down's Syndrome Screening test has the highest detection rate?

Back 79

Integrated (NT, PAPP-A, quad screen)- 94-96%
&
Stepwise Sequential - 95%

Front 80

Should Women who have had first-trimester screening for aneuploidy undergo independent second-trimester serum screening in the same pregnancy?

Back 80

NO!

When these test results are interpreted independently, the false-positive rates are additive, leading to many more unnecessary invasive procedures (11% to 17%).

After first-trimester screening, subsequent second-trimester Down syndrome screening is not indicated, unless it is being performed as a component of an integrated test, stepwise sequential, or contingent sequential test.

Front 81

A fetus with a Cystic Hygroma has a high likelihood of developing what Aneuploidy?

Back 81

45X- Turners

Front 82

Fetuses with Complete AV Canal and duodenal atresia are associated with what Trisomy?

Back 82

21- Down's

Front 83

The average maternal serum AFP level in Down syndrome pregnancies is reduced, Intact hCG is increased, and unconjugated estriol is reduced. When the levels of all three markers (triple screen) are used to modify the maternal age-related Down syndrome risk, the detection rate for Down syndrome is approximately 70%; approximately 5% of all pregnancies will have a positive screen result. Typically, the levels of all three markers are reduced when the fetus has trisomy 18. Adding what to the triple screen improves the detection rate for Down's syndrome to about 80%?

Back 83

Adding **inhibin A** to the triple screen (quadruple screen) improves the detection rate for Down syndrome to approximately 80

Front 84

In the _______ trimester, gross abnormalities, such as cardiac defects, as well as a group of subtle sonographic markers (soft markers) may be associated with an increased risk for Down syndrome in certain women.

Back 84

SECOND

Although findings of soft markers do not significantly increase the risk of Down syndrome, they should be considered in the context of first-trimester screening results, patient's age, and history.

Front 85

Maternal serum AFP is used to screen for NTDs, congenital structural abnormalities of the brain and vertebral column.

TRUE OR FALSE:
Most affected pregnancies can be identified by an elevated maternal serum AFP level for a singleton pregnancy.

Back 85

TRUE.

Maternal serum AFP evaluation is an effective screening test for NTDs and should be offered to all pregnant women, unless they plan to have amniotic AFP measurement as part of prenatal diagnosis for chromosomal abnormalities or other genetic diseases.

Front 86

All of the following are considered Ultrasonographic soft markers for what abnormality?

Nuchal fold
Intracardiac echogenic focus
Mild ventriculomegaly
Echogenic bowel
Shortened femur or humerus
Absent nasal bone
Pyelectasis

Back 86

Down Syndrome

Front 87

______ _______ has been shown to prevent recurrence and occurrence of neural tube defects.

Back 87

FOLIC ACID. Because most individuals at increased risk do not know it until they have an affected child, all women should be advised to take a vitamin that contains at least 0.4 mg of folic acid prior to conception.

Front 88

For women who previously have had a child with a neural tube defect, the recommended dose of folic acid is ____mg daily.

Back 88

4 mg daily

Front 89

What does an "Integrated Screening" approach to detecting Down Syndrome include?

Back 89

The results of both first-trimester and second-trimester screening and ultrasound can be combined to increase their ability to detect Down syndrome.

This “integrated” approach to screening uses both the first-trimester and second-trimester markers to adjust a woman's age-related risk of having a child with Down syndrome.

Front 90

________ screening provides the highest sensitivity with the lowest false-positive rate.

Back 90

INTEGRATED

Front 91

Who should undergo Carrier Testing?

Back 91

Individuals who have a family history of a specific genetic disorder but who show no signs of the disorder themselves, may undergo carrier testing to determine the risk of passing the disorder on to their offspring. In addition, individuals with certain ethnic backgrounds predisposed to genetic disorders may undergo carrier testing.

Front 92

What is a "Direct Test"?

What are some examples of diseases that have a Direct Testing available?

Back 92

Genes responsible for many diseases have been located, and direct testing for the presence of a specific mutation can be performed.

Examples of diseases for which direct tests exist are Tay-Sachs disease, hemophilia A, cystic fibrosis, sickle cell disease, Canavan disease, familial dysautonomia, and thalassemia.

Front 93

What is "Indirect Testing" and how does it relate to Restriction fragment- length polymorphisms (RFLPs)?

Back 93

Indirect testing refers to the process of determining DNA sequences of specific length that are linked to a mutation. These sequences, called restriction fragment-length polymorphisms (RFLPs), can be tested for by the Southern blot technique. Indirect testing is not as accurate as direct testing.

For disorders where disease-causing mutations have not been delineated, indirect testing is required.

Front 94

Prenatal analysis of DNA requires fetal nucleated cells, currently obtained by what procedures?

Back 94

amniocentesis, CVS, or percutaneous umbilical blood sampling (PUBS).

Front 95

Is amniocentesis considered safe?

Back 95

Studies have confirmed the safety of amniocentesis as well as its cytogenic diagnostic accuracy (greater than 99%).

The risk of pregnancy loss is less than 1%. Complications, which occur infrequently, include transient vaginal spotting or amniotic fluid leakage in approximately 1% to 2% of all cases, and chorioamnionitis in less than 1 in 1000 cases. The perinatal survival rate in cases of amniotic fluid leakage following midtrimester amniocentesis is greater than 90%.

Front 96

Amniocentesis Procedure...

Back 96

Amniocentesis is the withdrawal of 20 to 40 mL of amniotic fluid transabdominally, under concurrent ultrasound guidance, with a 20-gauge to 22-gauge needle. Traditional genetic amniocentesis is usually performed between 15 and 20 weeks' gestation. Direct analysis of the amniotic fluid supernatant is possible for AFP and acetylcholinesterase assays; such analyses permit detection of fetal NTDs and other fetal structural defects (e.g., omphalocele, gastroschisis).

Front 97

Amniocentesis during what stage of pregnancy has higher rate of pregnancy loss and complications?

Back 97

Early amniocentesis performed from 11 weeks to 13 weeks of gestation has significantly higher rates of pregnancy loss and complications than traditional amniocentesis. For these reasons, early amniocentesis **before 14 weeks of gestation should not be performed.**

Front 98

What is CVS?

Back 98

Chorionic villus sampling was developed to provide prenatal diagnosis in the first trimester. CVS is performed after 10 weeks of gestation by transcervical or transabdominal aspiration of chorionic villi (immature placenta) under concurrent ultrasound guidance.

Front 99

Is CVS considered as safe as Amniocentesis?

Which CVS approach has the highest risk of pregnancy loss?

Back 99

The rate of pregnancy loss associated with CVS appears to approach, and may be the same as, the loss associated with midtrimester (no sooner than 15 weeks!) amniocentesis.

**Transcervical** CVS carries a higher risk of pregnancy loss. Disorders that require analysis of amniotic fluid, such as NTDs, cannot be diagnosed with CVS. There is also a significant learning curve associated with the safe performance of CVS.

Front 100

CVS should not be preformed before ___ weeks gestation.

Back 100

10

Front 101

What is PUBS?

Back 101

Percutaneous umbilical blood sampling (PUBS), also known as cordocentesis, is usually performed after 20 weeks' gestation and has traditionally been used to obtain fetal blood for blood component analyses (e.g., hematocrit, Rh status, platelets), as well as cytogenetic and DNA analyses. The indications for PUBS are declining. One major benefit of PUBS is the ability to obtain rapid (18 to 24 hours) fetal karyotypes. However, with the advent of fluorescence in situ hybridization (FISH), PUBS has obviated the need for a procedure with more potential for complications.

Front 102

When would fetal skin sampling, fetal tissue (muscle, liver) biopsy, and fetoscopy be indicated?

Back 102

These procedures are used only for the diagnosis of rare disorders not amenable to diagnosis by less invasive methods.

Front 103

A karyotype is a photomicrograph of the chromosomes taken during __________, when the chromosomes have condensed. A separate image is made of each individual chromosome from this micrograph. The chromosomes are then matched to their homologue, so that the karyotype shows the chromosome pairs.

Back 103

METAPHASE

Because most fetal cells in amniotic fluid specimens obtained through amniocentesis are not in metaphase, these cells must first be cultured (grown) in order to perform a karyotype analysis.

Front 104

What is an advantage to using CVS over Amniocentesis to obtain the materials needed for a karyotype?

Back 104

An advantage of CVS over amniocentesis is that CVS allows for rapid cytogenetic and DNA analyses, because cytotrophoblasts obtained from first-trimester placentas are more likely to be in metaphase than amniotic fluid cells.

Front 105

What is FISH?

Which chromosomes is it done for?

Back 105

Fluorescence in situ hybridization (FISH) is a technique that involves fluorescent labeling of genetic probes for specific chromosomes, most commonly:
****13, 18, 21, X, and Y****
FISH can identify abnormalities in chromosome number, and results are usually available by 48 hours. Although FISH analysis has been shown to be accurate, false-positive and false-negative results have been reported. Therefore, clinical decision making should be based on information from FISH and either a traditional karyotype, ultrasound findings, or a positive screening test result.

Front 106

What is Spectral Karyotyping? What chromosomes can it be done for?

Back 106

Spectral karyotyping (SKY) is similar to FISH, but can be done for **all** chromosomes. SKY is useful in detecting translocations.

Front 107

What are the 3 key elements in genetic counseling?

Back 107

The key elements in genetic counseling are:

Accurate diagnosis
Communication
Nondirective presentation of options.

The counselor's function is not to dictate a particular course of action, but to provide information that will allow couples to make informative decisions.

Front 108

Counseling is directed at helping the patient or family in the following areas:(Just read them)

Back 108

Comprehending the medical facts, including the diagnosis, probable course of the disorder, and available management

Appreciating the way in which heredity contributes to the disorder and the risk of occurrence or recurrence in specific relatives

Understanding the options for dealing with the risk of recurrence, including prenatal genetic diagnosis

Choosing the course of action that seems appropriate in view of the risk and the family's goals and act in accordance with that decision

Making the best possible adjustment to the disorder in an affected family member and to the risk of recurrence in another family member

Front 109

True or False:

It is now known that certain breast and ovarian cancers have a genetic predisposition.

Back 109

TRUE!

Genetic tests have been developed for the detection of some of these genes.

Keep in mind...The most important initial step in identifying women at high risk for hereditary cancers is a thorough family history.

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What are some clues to possible hereditary cancers that can be obtained from the history?

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History of cancers in first-degree relatives

Cancers occurring at young ages

Cancers in multiple generations

Many different cancers in one individual.

Based on these findings, further testing and genetic counseling may be indicated.

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Which 2 genes have been identified as responsible for the hereditary forms of both breast and ovarian cancer?

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BRCA1 and BRCA2

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What are the Criteria developed by the U.S. Preventative Services Task Force for BRCA testing referral? (5)

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Two first-degree relatives with breast cancer, with at least one diagnosed at under age 50

Three or more first-degree or second-degree relatives with breast cancer at any age

A first-degree or second-degree relative with breast and ovarian cancer

Two or more first-degree or second-degree relatives with ovarian cancer

A male relative with breast cancer

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Because the incidence of breast cancers linked to BRCA is higher in Ashkenazi Jewish women, the testing criteria for them are slightly different. Testing for BRCA in this population is indicated if either of what 2 criteria are present?

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Any first-degree relative with breast or ovarian cancer

Two second-degree relatives on the same side of the family with breast or ovarian cancer

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What hereditary syndrome increases the risk for colon cancer?

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HNPCC type A- (hereditary nonpolyposis colorectal cancer type A ), or Lynch I syndrome

A family history of colon, endometrial, ureteral, or renal cancers should alert the clinical to screen for the HNPCC-linked genes.

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What is HNPCC type B, or Lynch II syndrome?

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HNPCC type B, or Lynch II syndrome, is an autosomal dominant inherited syndrome that increases the risk for all of the cancers in Lynch I syndrome, as well as for ovarian, gastric, and pancreatic cancers. Individuals or families who meet certain criteria, which include the presence of HNPCC in two successive generations and the diagnosis of HNPCC in at least three relatives, can undergo genetic testing to determine whether they have the defective gene.