Genetics: Program

Front 1

Advanced Maternal Age is associated with increased incidence of what type of mutations?

Back 1

Single gene mutations and the birth prevalence of fetal chromosome abnormalities 21, 18, and 13.

Front 2

The maternal age that amniocentesis is routinely offered.

Back 2

35 years or older.

Front 3

What type of laboratory testing is recommended for advanced maternal age?

Back 3

Amniocentesis or chorionic villus sampling. AFP marker screen patient risk for Down syndrome and trisomy 18. High resolution ultrasound may also refine risk if AFP is positive.

Front 4

At what age is a man considered to be advanced in paternal age?

Back 4

>45 y/o

Front 5

The risk for chromosomal abnormalities is 30% greater in the second trimester than at birth. Why?

Back 5

Risk for chromosomal abnormalities is about 30% greater in the second trimester than at birth due to fetal loss of chromosomally abnormal fetuses in the 3rd trimester.

Front 6

AFP multiple marker screening can refine the risk of Down syndrome and trisomy 18. What is the percentage of cases that will be identified using this method in women of advanced maternal age?

Back 6

85% of Downs syndrome and trisomy 18; 47% of other trisomies and 44% of sex aneuploidies.

Front 7

What are the diseases that have increased occurrence rates in the following populations? What are the carrier rates?

1. SE Asians
2. Mediterraneans
3. African Americans

Back 7

1. SE Asians: alpha-thalassemia (--,aa) 15-20% carriers.

2. Mediterranians: beta-thalassemias, up to 5% carriers.

3. African Americans: Sickle cell, 10% are carriers.

Front 8

What is the risk for two carriers of sickle cell anemia to have an affected child?

Back 8

1/4

Front 9

What is the risk for two Southeast Asian carriers of a-thalassemmia trait to have a child affected with severe fatal anemia?

Back 9

1/4

Front 10

What is the risk of two African American carriers of a-thalassemmia trait to have a child with severe fatal anemia?

Back 10

No demonstrated risk

Front 11

Which couples are at risk of having a child with hemoglobin H disease (a-thalassemmia with moderately severe anemia)?

Back 11

If one member of the couple is African-American/Black and the other is Southeast Asian, then the risk is significant.

Front 12

What diseases have an increased occurrence rate among Ashkenasi Jews?

Back 12

Tay-sachs Disease (TSD) and Canavan Disease

Front 13

What is the carrier frequency of TSD and CD among Ashkenasi Jews?

Back 13

TSD: 1/31
CD: 1/35 to 1/40

Front 14

What is the defective enzymes in TSD and CD?

Back 14

TSD: hexosaminidase A
CD: Aspartoacylase (Breaks down N-acetylaspartic acid)

Front 15

How are TSD and CD carriers detected?

Back 15

TSD: Biochemical testing for Hex A levels in serum or leukocytes.
CD: Biochemical testing is not good for carriers and non-carriers.

Front 16

What is the risk of two carriers of TSD or CD having an affected child?

Back 16

1/4

Front 17

Occurrence risk for an open NTD in the general population?

Back 17

1/1000

Front 18

Recurrence risk if affected individual is your patient (the baby’s mother) or the baby’s father or the baby’s sibling?

Back 18

3/100

Front 19

Recurrence risk if affected individual is the baby’s grandparent or aunt or uncle?

Back 19

1/100

Front 20

Types of neural tube defects (of greatest clinical significance)?

Back 20

anencephaly
encephalocele
spina bifida cystica
spina bifida occulta

Front 21

Prenatal diagnostic tests used to detect NTD? Percentage identified?

Back 21

High resolution targeted ultrasound examination at 16-20 weeks gestation - no percentage given

Amniocentesis with amniotic fluid AFP - ~98%

Acetylcholinesterase testing - ~98%

AFP serum - 80-90%

Front 22

Folic acid reduces risk of NTD. How much is needed? When should it be taken? How much should be taken by a patient who has had a previous pregnancy affected with a NTD?

Back 22

Women who can become pregnant should take 0.4 mg/day; it is best that women take folic acid before they become pregnant.
Women with a previous NTD pregnancy are recommended to take 4.0mg folic acid/day

Front 23

Causes of inherited mental retardation?

Back 23

Cytogenetic disorders, single gene dysmorphic syndromes

Front 24

What are non-inherited causes of mental retardation?

Back 24

Intrauterine infections, teratogenic syndromes, inborn errors of metabilism, injury/insult, CNS malformations, neurocutaneous disorders

Front 25

What is the prevalence of Down Syndrome?

Back 25

1/700 to 1/1000

Front 26

What is non-disjunction?

Back 26

Cell division error that occurs during meiosis and results in an extra chromosome.

Front 27

What is the recurrence risk for a second child with full Trisomy 21?

Back 27

1% or age-related risk

Front 28

What laboratory testing is recommended for children with Down syndrome?

Back 28

Fetal chromosome analysis (amniotic fluid or chorionic villi)

Front 29

What percentage of Down syndrome cases are due to translocations or rearrangements?

Back 29

3-5%

Front 30

If a child has Down syndrome due to a translocation, what additional laboratory testing is recommended? Why?

Back 30

Parent chromosome analysis, because the translocation may have been the result of a balanced translocation in one of the parents

Front 31

Number of liveborn infants with detectable chromosomal abnormalities?

Back 31

1/150-200

Front 32

What are the most common chromosomal abnormalities detected?

Back 32

Chromosome rearrangements, sex chromosome abnormalities

Front 33

Inheritance pattern of Cystic Fibrosis?

Back 33

Autosomal recessive.

Front 34

Carrier frequency of CF in the Northern European Caucasian population? Disease frequency?

Back 34

1/25 carrier frequency
1/2500 disease frequency

Front 35

Protein affected in CF?

Back 35

CFTR (chloride transport channel)

Front 36

In CF, how are carriers detected? What percentage of carriers are detected in the Caucasian population?

Back 36

Carriers are detected through DNA testing, 90% of Caucasian carriers are detected this way.

Front 37

What is probability of an affected child if both parents have been tested and both carry a CF mutation?

Back 37

1/4

Front 38

In CF, what is probability of an affected child if both parents were tested, and neither one tested positive?

Back 38

0.25%
(0.1 x 0.1 x .25)

0.1 = rare, undetected mutation risk

Front 39

Fragile X is the most common form of inherited mental retardation. What is the prevalence of Fragile X? Why is it different for males and females?

Back 39

1/1500 to 1/2500 males
1/2500 females

Front 40

What is a premutation carrier? How are they detected? What is the risk of their child inheriting Fragile X syndrome?

Back 40

An individual who has 50-200 repeats of CGG in their FMR-1 gene. This is detected by cytogenic testing. If the carrier is female, their risk of having a child with Fragile X is large. If a carrier is male, there is no risk to their direct offspring.

Front 41

What is a normal transmitting male? What is the risk of his children inheriting Fragile X Syndrome?

Back 41

A male who carries a premutation. He is unaffected and each of his daughters will receive the altered gene but they will not be affected, although they will have an increased risk of having a child with Fragile X.

Front 42

What is inheritance pattern of DMD?

Back 42

There are X linked recessive.

Front 43

What is the risk of a carrier of DMD having an affected child?

Back 43

25% (1/2 she has a boy, 1/2 that gets affected chromosome).

Front 44

What is the risk of a woman having a second child with DMD?

Back 44

Variable, 30% of mutations arise de novo so the mother must be tested to see if she is a carrier before this can be determined

Front 45

What is the risk of a woman having a child with DMD if her brother was affected?

Back 45

There’s a 50% chance she’s a carrier of DMD so the risk of having offspring with DMD would be (1/2)(1/2)(1/2) = 1/8. 1/2 she's a carrier, 1/2 she has a boy, and 1/2 it gets the affected gene.

Front 46

What is the risk of a woman having a second child with DMD if her brother was affected?

Back 46

This woman is now a confirmed carrier, increasing her risk to ¼.

Front 47

What is the risk of a woman having a child with DMD if her husband's brother was affected?

Back 47

Low if father is unaffected

Front 48

What is the incidence of DMD?

Back 48

1 in 3,500 males

Front 49

What is the main difference between Duchenne and Becker muscular dystrophy?

Back 49

Becker is a milder form of the same disease – it has later onset and slower progression of symptoms

Front 50

What is the inheritance pattern of Myotonic Dystrophy?

Back 50

Autosomal dominant.

Front 51

Name of defective gene that causes Myotonic Dystrophy?

Back 51

Myotonin protein kinase gene on chromosome 19.

Front 52

How many CTG trinucleotide repeats are found in a normal individual, one affected with late onset, less severe MD, and one effected with early onset, more severe MD?

Back 52

Normal < 50
Late onset, less severe = 50 – 100
Early onset, more severe = >1000

Front 53

What is the inheritance pattern of Hemophilia A?

Back 53

X-linked

Front 54

What is the risk of a carrier of hemophilia A having an affected child?

Back 54

50% chance for males to be affected.

Front 55

What is the risk of an affected individual having an affected child?

Back 55

Risk for fetus is minimal. Male to male transmission is not possible. All daughters of a male with hemophilia will be carriers.

Front 56

What is the risk of a woman having a child with Hemophilia A if her father was affected?

Back 56

1/2 chance for male children to be affected

Front 57

What is the risk of a woman having a child with Hemophilia A if her husband's father was affected?

Back 57

Minimal risk. No male to male transmission

Front 58

What is the most common form of inherited bleeding disorder?

Back 58

Von Willebrand Disease

Front 59

What is the chance that an individual affected with the most common form of von Willebrand disorder will have an affected child?

Back 59

The most common, Type I, is autosomal dominant so 50% of offspring will be affected.

Front 60

What is the mode of inheritance in Huntington disease?

Back 60

Autosomal dominant

Front 61

What is chance of an affected individual having an affected child?

Back 61

50%

Front 62

How are carriers of this disease detected?

Back 62

Detect expansion in the number of copies of CAG

Front 63

What is anticipation?

Back 63

Symptoms occur at earlier ages in successive generations.

Front 64

Why are asymptomatic relatives of affected individuals with Huntington's offered testing only through a limited number of centers?

Back 64

Testing will provide supportive counseling and anticipatory guidance as well as DNA analysis.

Front 65

What is the inheritance pattern of NF1?

Back 65

Autosomal dominant

Front 66

What is the prevalence of NF1?

Back 66

1/3000

Front 67

What is the recurrence risk if a couple has one child with NF1?

Back 67

50%

Front 68

What is the recurrence risk if one parent is affected with NF1?

Back 68

50%

Front 69

What is the affected protein in NF1? What is its function?

Back 69

Neurofibromin, which is a tumor suppressor protein.

Front 70

What is the prevalence of CHD?

Back 70

1/100 live born babies (4-5 X higher in stillbirths)

Front 71

What is the most common inheritance pattern for CHD?

Back 71

Most (95%) are multifactorial. 5-6% are associated with chromosomal abnormalities, 3-5% Mendelian syndromes, and 2% environmental.

Front 72

What is the recurrence risk if a couple has one child affected with CHD? Two?

Back 72

Risk with 1 affected child is 1-3%. Risk with 2 affected children is 5-10%.

Front 73

What is recurrence risk if the mother had CHD?

Back 73

2.5-18%

Front 74

What test is used for prenatal diagnosis of a CHD?

Back 74

Fetal echocardiogram

Front 75

Incidence of cleft lip with or without cleft palate?

Back 75

1/1,000 live births

Front 76

Most common pattern of inheritance for cleft lip with or without a cleft palate?

Back 76

85-90% of cases are isolated defects attributed to multifactorial inheritance

Front 77

Prevalence of congenital major malformations?

Back 77

3-5% of infants have major malformations; 1% of infants have multiple malformations.

Front 78

Etiological categories that are possible causes of isolated birth defects?

Back 78

Malformation, disruption, deformation, dysplasia

Front 79

Most common inheritance pattern for congenital malformations?

Back 79

Most are multifactorial. Some are Mendelian or chromosomal syndromes.

Front 80

What is a common genetic cause of repeated pregnancy loss?

Back 80

Chromosomal abnormalities

Front 81

In couples that have experienced two or more pregnancy losses, what is the frequency it is caused by this genetic abnormality?

Back 81

In 5% of these couples one member will carry a balanced chromosome rearrangement.

Front 82

What are the four major modes of inheritance of single gene disorders, and segregation of traits?

Back 82

Autosomal dominant inheritance,
autosomal recessive inheritance,
X-linked inheritance,
multifactorial inheritance

Front 83

The incidence of what type of disorders are increased with consanguinity?

Back 83

Individuals who are related can share an increased number of genes. This increases the risk for inherited diseases (especially recessive disorders) in offspring.

Front 84

What is risk of serious abnormality in a mating between first cousins?

Back 84

Couples in a third degree relative-relationship (cousins) have a 6-8% chance of having offspring with a birth defect. Double the risk of being not related.

Front 85

What is the risk of a serious birth defect in the general population?

Back 85

Couples in the general population (not related), have a 3-4% risk of having offspring with a birth defect.

Front 86

What is risk of cystic fibrosis in a mating between first cousins, if they have another shared cousin
With CF?

Back 86

Assume that grandparents are AA x Aa. This would mean that the parents of the proband each have a ½ chance of being a carrier, as does the proband and his/her partner (1/2*1/2*1/2*1/2). The risk of their child having the disease is ¼. The answer is 1/64 chance.

Front 87

What is population risk in the Northern European Caucasian population for CF? (carrier and affected)

Back 87

1/25 carrier
1/2500 affected

Front 88

Women with IDDM (type I diabetes) are at increased risk for what abnormality in their pregnancies?

Back 88

Risk for fetal structural malformations is increased 6-16%

Front 89

What is the most important predictor of outcome for women with IDDM?

Back 89

Most important predictor is thought to be the degree of metabolic control.

Front 90

What is the most common problem seen in babies born to mothers with PKU?

Back 90

Maternal PKU effects on the fetus include mental retardation, microcephaly, heart defects, growth deficiency, and an increase in miscarriage.

Front 91

What is the cause of birth defects associated with maternal PKU?

Back 91

Although children of affected mothers have normal phenylalanine hydroxylase activity, the mother’s abnormally high phenylalanine content becomes concentrated in the fetus due to mass action. Fetal level can be 1.5 times that of the mother.

Front 92

How can maternal PKU be managed to reduce risk?

Back 92

If phenylalanine is maintained at less than 4 mg/dl, fetal phenylalanine will remain less than 6-7 mg/dl. The best outcomes are achieved through strict diet for the mothers prior to conception. But strict diet is beneficial as long as it is started prior to week 10 of gestation, with phenylalanine levels maintained below 10 mg/dl for the duration of the pregnancy.

Front 93

What is the most common form of mental retardation? Prevalence?

Back 93

The most common form of mental retardation is fetal alcohol syndrome.

1/300 children is affect with FAS-related mental retardation

Front 94

What are the four common procedures for prenatal diagnosis?

Back 94

Amniocentesis
Chorionic villus sampling
High resolution targeted ultrasound examination
Fetal echocardiography

Front 95

What prenatal diagnosis can be done the earliest? What does it detect?

Back 95

CVS: identify fetal chromosomal abnormalities. Done at 10 to 11 weeks gestation.