Chapter 16 - Week 6

Penetrance is the risk of being affected, use 1-p if you want to assume the person is a carrier who is not affected.

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When adding conditional probability for % of penetrance or visibility of symptoms, include (1-p) in the scenario where the person is a carrier. In scenarios where they are not a carrier, the conditional probability is just 1.

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Family History in Risk Assessment - Moderate Risk Factors

- One 1st degree with late or unknown onset - Two 2nd degree from same lineage with late or unknown onset

What is the new mutation risk of an X-linked lethal disorder?

1/3

A couple who are first cousins inquire about the chance of having a child affected with a genetic disorder. Their common maternal uncle has galactosemia, an autosomal recessive condition. The chance that they will have a child with galactosemia is what? A. 1/8 B. 1/16 C. 1/36 D. 1/64

C. 1/36

Family History in Risk Assessment - High Risk Factors

- Early age of onset in 1st degree relative - Two affected 1st degree relatives - One 1st degree with late or unknown onset; 1 affected 2nd degree with premature disease from same lineage - Two 2nd degree maternal or paternal relatives with at least 1 having premature onset - Three or more affected maternal or paternal relatives - Moderate risk family history on both sides

Family History in Risk Assessment - Average Risk Factors

- No affected relatives - Only 1 affected 2nd degree from one or both sides of the pedigree - No known family history - Adopted person with unknown family history

A "normal" sibling of someone affected with an autosomal recessive disease has what risk of being a carrier?

2/3

A mom who has a son affected with an X-linked lethal disorder has what risk of being a carrier?

2/3

A woman has a brother and a maternal uncle who died with severe hydrocephalus due to X-linked aqueductal stenosis caused by mutations in the L1CAM gene. She has two healthy sons. She is pregnant. The probability that her fetus is severely affected with hydrocephalus is about __________? A. 1/5 B. 1/8 C. 1/10 D. 1/20 E. 1/32

?

A couple comes to a prenatal genetic counseling appointment because they are concerned about their risk to have a baby with a specific rare autosomal recessive disorder which is more common in individuals of Mediterranean ancestry. The pregnant woman indicates she has a cousin with this disorder, and she has provided medical records showing that the cousin has been diagnosed both clinically and molecularly with this disorder. The woman's partner indicates that he has no family history of the disorder. Which of the following do you need to know in order to provide the most accurate risk assessment for the chances that their fetus will be affected? A. The partner's ancestry B. The age at which the cousin was diagnosed C. The patient's understanding about the natural history of the condition D. The patient's desire for invasive diagnostic prenatal testing E. The number of siblings the patient's partner has

? Not D

A man who is a known heterozygous carrier of oculocutaneous albinism marries his half cousin, with whom he shares a common paternal grandmother. What is the probability that this couple will produce a child with this fully penetrant, autosomal recessive disorder? A. 1/4 B. 1/8 C. 1/16 D. 1/32 E. 1/64

? Not D

uninformative negative test

A test that is negative but we don't know for certain if it was testing the gene of interest in the proband or if it was a true negative.

Which of the following statements is true in regards to recurrence risk counseling for a complex disorder using empirical risks? A. Empirical risk figures are often used to provide recurrence risk estimates for the chance for future offspring with aneuploidy once a couple has had a child with aneuploidy. B. Empirical risk numbers do not change over time so once a rigorous study has been completed, those figures can be used without revision. C. Because empirical risk figures are derived from large populations, such recurrence risks will apply to all families without exception. D. Empirical risk figures are no longer useful because technologies such as whole genome sequencing affords us enough information to give all patients individualized risk scores.

A. Empirical risk figures are often used to provide recurrence risk estimates for the chance for future offspring with aneuploidy once a couple has had a child with aneuploidy.

A couple, Tom and Bernadette, comes for genetic counseling because they are concerned that they are at risk for offspring with cystic fibrosis and they are considering starting a family. Tom's brother had a diagnosis of cystic fibrosis and passed away in his teens. Tom provides you with a molecular test report showing his brother's mutations. Tom's primary care physician arranged carrier screening for him and it was negative. Tom and Bernadette are nonconsanguineous and Bernadette indicates she is of Western European ancestry. What information would be most helpful to you in determining their future offspring's risk for cystic fibrosis? A. What mutations were included on the mutation screen Tom had B. Which Western European country/countries Bernadette's ancestors came from C. Whether Tom's parents are consanguineous D. The age at which Tom's brother was diagnosed

A. What mutations were included on the mutation screen Tom had

A 26-year-old woman of Norwegian descent seeks genetic counseling. Her brother died at age 8 of documented cystic fibrosis. Both of their parents are deceased. The woman undergoes DNA testing for 70 CF mutations, which collectively detects approximately 90% of CF carriers of northern European descent. Testing reveals that she is negative for all 70 mutations. What is the probability that she is a heterozygous carrier of CF? A. 2/3 B. 1/6 C. 1/5 D. 1/25

B 1/6

A woman and her husband discover they are both carriers of Tay Sachs after their fourth child is diagnosed with Tay Sachs disease, an autosomal recessive disorder. The couple had previously had three healthy children. After their fourth child is diagnosed with Tay Sachs disease, they go on to have another two healthy children that do not have Tay Sachs disease. What is the chance that their seventh child will have Tay Sachs disease? A. 1 in 7 B. 1 in 4 C. 1 in 128 D. 1 in 14

B. 1 in 4

The scientific literature supports the idea that once a couple has had a child with a neural tube defect, the empirical recurrence risk for subsequent offspring is around 4%; however, recent population data suggests recurrence risks are likely much lower than previously published. Why? A. As prenatal diagnostic imaging via ultrasound improves, more babies with neural tube defects are being identified before birth. B. Widespread folate supplementation has drastically decreased recurrence risks for this class of birth defect. C. More couples are choosing to terminate pregnancies affected with neural tube defects. D. Neural tube defects are primarily caused by teratogenic exposures to drugs which are no longer prescribed.

B. Widespread folate supplementation has drastically decreased recurrence risks for this class of birth defect.

A father is known to be affected with Beals syndrome, an autosomal dominant connective tissue disorder. He wants his child to be seen in the genetics clinic for an evaluation. The geneticist notes that in 80% of cases the ears have a crumpled appearance. The child's ear appears normal; what is his adjusted risk of being affected with this condition? A. 1/2 B. 1/6 C. 1/11 D. 1/25

B. 1/6

Rebekah, a 27-year-old woman is screened for a fully penetrant autosomal dominant disorder. Clinical symptoms for this disease do not generally appear until the fourth decade of life. Rebekah's mother had the disease and died in her early 40s. The screening test detects affected individuals with a 98% sensitivity and a 5% false positive rate. Rebekah tests positive. What now is the best estimate of her risk of developing the disease? A. 90% B. 95% C. 97.5% D. 98% E. 99%

B. 95%

A woman who has two brothers and a maternal uncle with non-specific X-linked mental retardation is referred for genetic counseling. She already has two unaffected sons. There are no diagnostic tests available to help determine whether or not she is a carrier. Which of the following is correct? A. The prior probability that she is a carrier is 1 in 4 B. The probability that she is a carrier can be calculated using Bayes' Theorem to be 1 in 5 C. The probability that her next son will be affected or that her next daughter will be a carrier is 1 in 5 D. The probability that the maternal grandmother is a carrier is 1 in 2

B. The probability that she is a carrier can be calculated using Bayes' Theorem to be 1 in 5

A 22-year-old man is at 50% risk of having inherited a mutation for a dominantly inherited disorder. He has no signs of the disorder, but the condition displays age-dependent penetrance, so that 20% of individuals at age 22 would expect to be affected. What is his approximate risk of having inherited the mutation? Answers: A. 0.86 B. 0.52 C. 0.44 D. 0.24 E. 0.20

C. 0.44

A pregnant couple comes for genetic counseling because they recently discovered they have the same father who happens to have an autosomal recessive form of albinism. What is the chance that their child will also have albinism? A. 1/2 B. 1/3 C. 1/4 D. 1/6 E. 1/9

C. 1/4

Which of the following statements is true in regards to first-cousin matings? A. First-cousin matings are at an approximately 10-fold increased risk for birth defects as compared to nonconsanguineous matings. B. First-cousins who have had one offspring with a birth defect are at no higher risk for subsequent offspring with birth defects than they were based on consanguinity alone. C. First-cousin matings are about twice as likely to result in birth defects as the offspring of nonconsanguineous matings. D. The offspring of first-cousin matings are at increased risk for single gene disorders but not for isolated birth defects.

C. First-cousin matings are about twice as likely to result in birth defects as the offspring of nonconsanguineous matings.

Many disorders are not caused by single gene inheritance, but are multifactorial. In counseling situations involving these disorders, how are recurrence risks identified? A. Single gene inheritance risks are multiplied by a multifactorial fraction, chosen to represent the contribution from other genetic factors plus the environmental influence B. Bayes' theorem is applied, using modifications of the 'prior' risk calculation utilized among single-gene defects C. The risks are determined empirically, based on previous observations of disease recurrence among actual families D. Recurrence risks cannot be determined for non-Mendelian disorders

C. The risks are determined empirically, based on previous observations of disease recurrence among actual families

John is a 42-year-old man with hemophilia A. John's daughter, Susan, is married to Fred, who also has hemophilia A. Susan and Fred are expecting their first child, and ultrasound demonstrates the fetus is a boy. The probability that Fred and Susan's new son will have hemophilia A is closest to which of the following? A. 1 B. 3/4 C. 2/3 D. 1/2 E. 1/4

D. 1/2

A molecular genetic test for a specific autosomal recessive disease can identify 80% of carriers. The test identifies a man as a definite carrier. Assuming a population carrier risk of 1 in 25, what is the probability that this man's spouse is a carrier if she had a negative genetic test? A. Slightly greater than 0.032 B. Exactly 0.032 C. Slightly less than 0.032 D. Slightly greater than 0.008 E. Exactly 0.008

MAYBE D. Slightly greater than 0.008

Published consanguinity risks may be slightly elevated due to....

being derived from communities in which first cousin marriages are widespread and could have a higher degree of relationship than expected.

If a variant has been seen in _____% of the populate it is less likely to be disease causing

greater than 2%

Having a first degree relative with a common disease of adulthood raises an individual's risk for that disease approximately _______ relative to the general population

twofold to threefold