Carrier screening for genetic disorders US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Carrier screening for genetic disorders. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Carrier screening for genetic disorders US Medical PG Question 1: A genetic counselor sees a family for the first time for genetic assessment. The 24-year-old businessman and his 19-year-old sister are concerned about having a mutant allele and have decided to get tested. Their grandfather and great aunt both have Huntington’s disease which became apparent when they turned 52. Their father who is 47 years old appears healthy. The geneticist discusses both the benefits and risks of getting tested and orders some tests. Which of the following tests would best provide evidence for whether the siblings are carriers or not?
- A. Gel electrophoresis
- B. Restriction enzyme digestion products
- C. Polymerase chain reaction (Correct Answer)
- D. Pyrosequencing
- E. DNA isolation and purification
Carrier screening for genetic disorders Explanation: ***Polymerase chain reaction***
- **PCR is the essential first step** for detecting Huntington's disease carrier status by **amplifying the CAG trinucleotide repeat region** in the *HTT* gene.
- After PCR amplification, **fragment analysis** (capillary electrophoresis or gel electrophoresis) is used to determine the exact number of CAG repeats, which distinguishes carriers (≥36 repeats) from non-carriers (<27 repeats).
- Among the options listed, **PCR is the critical enabling technology** without which carrier testing cannot proceed.
- The complete diagnostic test is called "CAG repeat analysis" or "trinucleotide repeat analysis," which uses PCR as its foundation.
*Gel electrophoresis*
- **Gel electrophoresis** can be used to visualize the size of PCR-amplified DNA fragments and may help distinguish expanded repeats from normal-sized alleles.
- However, modern laboratories typically use **capillary electrophoresis** (automated fragment analysis) for more precise repeat counting.
- Gel electrophoresis alone, without prior PCR amplification, cannot detect the CAG repeat expansion.
*Restriction enzyme digestion products*
- Huntington's disease is caused by a **CAG trinucleotide repeat expansion**, not a point mutation that creates or abolishes restriction enzyme sites.
- **Restriction fragment length polymorphism (RFLP)** analysis is not the primary method for detecting dynamic repeat expansions.
- This approach was historically used for linkage analysis before direct repeat testing became available.
*Pyrosequencing*
- **Pyrosequencing** is designed for **sequencing short DNA stretches** and detecting single nucleotide polymorphisms (SNPs).
- It is **not suitable for quantifying long trinucleotide repeat expansions** like those in Huntington's disease, where repeat numbers can range from 10 to over 100.
- **Fragment analysis** is the standard method for measuring repeat length, not sequencing.
*DNA isolation and purification*
- **DNA isolation** is a necessary preliminary step for any genetic testing but provides no diagnostic information by itself.
- It simply extracts genomic DNA from blood or tissue samples, which must then be analyzed using specific molecular techniques like PCR and fragment analysis.
Carrier screening for genetic disorders US Medical PG Question 2: A 19-year-old male from rural West Virginia presents to his family medicine doctor to discuss why he is having trouble getting his wife pregnant. On exam, he is 6 feet 2 inches with a frail frame and broad hips for a male his size. He is noted to have mild gynecomastia, no facial hair, and small, underdeveloped testes. He claims that although he has a lower libido than most of his friends, he does have unprotected sex with his wife. His past medical history is notable for developmental delay and difficulties in school. What is the most likely chromosomal abnormality in this patient?
- A. Trisomy 13
- B. 45: XO
- C. Trisomy 21
- D. 47: XYY
- E. 47: XXY (Correct Answer)
Carrier screening for genetic disorders Explanation: ***47: XXY***
- The patient's presentation with **infertility**, small testes, **gynecomastia**, eunuchoid body habitus (tall, frail frame, broad hips), lack of facial hair, and **developmental delay** are classic features of **Klinefelter syndrome (47, XXY)**.
- This chromosomal abnormality leads to primary **hypogonadism** due to the presence of an extra X chromosome in males.
*Trisomy 13*
- Trisomy 13, or **Patau syndrome**, is characterized by severe developmental anomalies, including **cleft lip and palate**, polydactyly, and severe neurological defects.
- Infants with Trisomy 13 rarely survive beyond the first year and do not present with the described signs of hypogonadism or gynecomastia in adolescence.
*45: XO*
- **45, XO** or **Turner syndrome** affects females and is characterized by **short stature**, primary amenorrhea, webbed neck, and **gonadal dysgenesis (streak gonads)**.
- This karyotype is incompatible with a male phenotype and the symptoms described.
*Trisomy 21*
- Trisomy 21, or **Down syndrome**, is associated with distinct facial features, intellectual disability, and congenital heart defects.
- While individuals with Down syndrome may have fertility issues, they do not typically present with the specific combination of **gynecomastia**, eunuchoid habitus, and **small testes** seen in this patient.
*47: XYY*
- **47, XYY syndrome** is associated with increased height and potentially some learning difficulties, but typically does not cause the significant **hypogonadism**, **gynecomastia**, or **small testes** seen in this patient.
- Men with 47, XYY usually have normal sexual development and fertility, though some may experience learning disabilities or behavioral problems.
Carrier screening for genetic disorders US Medical PG Question 3: A 35-year-old woman gravida 2, para 1, comes to the physician for her first prenatal visit. Pregnancy and delivery of her first child were uncomplicated. She is not sure about the date of her last menstrual period. Pelvic examination shows a uterus consistent in size with a 10-week gestation. An ultrasound examination confirms the gestational age and shows one fetus with no indication of multiple gestations. During counseling on pregnancy risks and possible screening and diagnostic tests, the patient states she would like to undergo screening for Down syndrome. She would prefer immediate and secure screening with a low risk to herself and the fetus. Which of the following is the most appropriate next step in management at this time?
- A. Nuchal translucency, pregnancy-associated plasma protein-A, human chorionic gonadotropin
- B. Maternal serum α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A
- C. Chorionic villus sampling
- D. Amniocentesis
- E. Cell-free fetal DNA testing (Correct Answer)
Carrier screening for genetic disorders Explanation: ***Cell-free fetal DNA testing***
- This is the most appropriate choice given the patient's desire for **immediate and secure screening with low risk** because it is a **non-invasive prenatal screening (NIPS)** method offering high sensitivity and specificity for Down syndrome, particularly in higher-risk pregnancies.
- It involves a simple maternal blood draw and can be performed as early as **10 weeks of gestation**, perfectly aligning with the patient's current gestational age and desire for early screening.
*Nuchal translucency, pregnancy-associated plasma protein-A, human chorionic gonadotropin*
- This combination represents the **first-trimester combined screen**, which is typically performed between 11 and 14 weeks of gestation. While suitable for early screening, **cell-free DNA testing offers higher detection rates and lower false-positive rates** for Down syndrome.
- The patient specifically asked for the most **secure and least risky** screening, and NIPS outperforms the combined screen in terms of diagnostic accuracy for aneuploidies.
*Maternal serum α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A*
- This refers to the **quad screen**, which is typically performed in the **second trimester (15-20 weeks)**, making it too late for the patient's desire for immediate screening at 10 weeks gestational age.
- While a widely used screening tool, the quad screen has a **lower detection rate** for Down syndrome compared to cell-free DNA testing.
*Chorionic villus sampling*
- **Chorionic villus sampling (CVS)** is a **diagnostic, invasive procedure** that carries a small risk of miscarriage (approximately 1 in 455 or 0.22%) and is not a screening test.
- Although it can be performed earlier (typically between 10 and 13 weeks), the patient specifically requested a **low-risk screening** option, which CVS is not.
*Amniocentesis*
- **Amniocentesis** is also an **invasive diagnostic procedure** with a risk of miscarriage (approximately 1 in 900 or 0.11%) and is typically performed in the **second trimester (15-20 weeks)**.
- This option is unsuitable because the patient is at 10 weeks gestation and desires **immediate and low-risk screening**, not a diagnostic procedure with procedural risks a few weeks later.
Carrier screening for genetic disorders US Medical PG Question 4: A healthy 29-year-old nulligravid woman comes to the physician for genetic counseling prior to conception. Her brother has a disease that has resulted in infertility, a right-sided heart, and frequent sinus and ear infections. No other family members are affected. The intended father has no history of this disease. The population prevalence of this disease is 1 in 40,000. Which of the following best represents the chance that this patient’s offspring will develop her brother's disease?
- A. 25%
- B. 66%
- C. 0.2% (Correct Answer)
- D. 0.7%
- E. 1%
Carrier screening for genetic disorders Explanation: ***0.2%***
- The brother's symptoms (infertility, right-sided heart, frequent infections) are characteristic of **Kartagener syndrome**, a form of **primary ciliary dyskinesia (PCD)**, which has an **autosomal recessive** inheritance pattern.
- Since the patient's parents are obligate heterozygotes (carriers), the patient has a 2/3 chance of being a carrier. Given the population prevalence of 1/40,000 for an autosomal recessive disease, the carrier frequency (2pq) is approximately **2 x sqrt(1/40,000) = 2 x 1/200 = 1/100**. The chance of her child inheriting the disease is (2/3 chance of patient being carrier) x (1/100 chance of partner being carrier) x (1/4 chance of affected offspring) = 2/1200 ≈ **0.00166 or 0.166%**, which is closest to 0.2%.
*25%*
- This would be the risk if both parents were known carriers, and it represents the chance of an affected offspring from two heterozygotes.
- In this scenario, the woman's partner's carrier status is unknown and based on population prevalence, making the overall risk much lower.
*66%*
- This is the probability that the patient (the healthy sister of an affected individual with an autosomal recessive disease) is a **carrier**.
- This value alone does not account for the partner's carrier status or the final Mendelian inheritance probability (1/4) for an affected child.
*0.7%*
- This percentage is too high; it might result from incorrect calculation of the population carrier frequency or misapplication of probabilities.
- The correct carrier frequency for the partner is 1/100, which is significantly lower than what would lead to a 0.7% final risk.
*1%*
- This value is also too high and likely results from a miscalculation of either the carrier frequency or the overall probability.
- A 1% chance would suggest a much higher population carrier frequency or a different inheritance scenario.
Carrier screening for genetic disorders US Medical PG Question 5: A 27-year-old G1P0 female presents for her first prenatal visit. She is in a monogamous relationship with her husband, and has had two lifetime sexual partners. She has never had a blood transfusion and has never used injection drugs. Screening for which of the following infections is most appropriate to recommend this patient?
- A. Syphilis and HIV
- B. Syphilis, HIV, and HBV (Correct Answer)
- C. Syphilis, HIV, HBV, and chlamydia
- D. Syphilis, HIV, and chlamydia
- E. No routine screening is recommended for this patient
Carrier screening for genetic disorders Explanation: ***Syphilis, HIV, and HBV***
- The **American College of Obstetricians and Gynecologists (ACOG)** and the **Centers for Disease Control and Prevention (CDC)** recommend universal screening for syphilis, HIV, and hepatitis B virus (HBV) in all pregnant women at the first prenatal visit.
- This **routine screening** is crucial due to the potential for vertical transmission and severe adverse outcomes for the neonate if untreated.
*Syphilis and HIV*
- While screening for syphilis and HIV is essential, it is **incomplete** as it omits HBV, which is also universally recommended for antenatal screening.
- This option does not align with the standard comprehensive screening guidelines for pregnancy.
*Syphilis, HIV, HBV, and chlamydia*
- Although syphilis, HIV, and HBV screening are appropriate, adding **chlamydia** to the universal prenatal screening for *all* pregnant women in the first trimester is not standard practice unless specific risk factors are present or local prevalence is high.
- Chlamydia screening is typically recommended for pregnant women who are **25 years or younger** or those with **risk factors** for sexually transmitted infections (STIs).
*Syphilis, HIV, and chlamydia*
- This option incorrectly includes chlamydia as a universal screen for all pregnant women while **omitting HBV**, which is universally recommended.
- Missing HBV screening leaves a critical gap in prenatal care, as it can be transmitted vertically and cause severe neonatal disease.
*No routine screening is recommended for this patient*
- This statement is incorrect as **universal screening** for syphilis, HIV, and HBV is recommended for all pregnant women, regardless of reported risk factors or monogamous relationships.
- Maternal infection can still occur, and screening helps prevent severe outcomes for both mother and child through timely detection and intervention.
Carrier screening for genetic disorders US Medical PG Question 6: A 46-year-old woman presents to her primary care physician for her annual examination. At her prior exam one year earlier, she had a Pap smear which was within normal limits. Which of the following health screenings is recommended for this patient?
- A. Colorectal screening (Correct Answer)
- B. Blood glucose and/or HbA1c screening
- C. Blood pressure at least once every 3 years
- D. Yearly Pap smear
- E. Bone mineral density screening
Carrier screening for genetic disorders Explanation: ***Colorectal screening***
- **Colorectal cancer screening** is generally recommended to start at age **45 years** for individuals at average risk.
- This patient is 46 years old, making immediate colorectal screening appropriate based on current guidelines.
*Blood glucose and/or HbA1c screening*
- **Blood glucose or HbA1c screening** for diabetes is recommended starting at age **35 for all adults** or earlier if there are risk factors such as obesity or a family history of diabetes.
- While this patient is 46, this screening should have already been initiated, and it is not the *most* uniquely recommended screening for this specific age that might have been overlooked.
*Blood pressure at least once every 3 years*
- **Blood pressure screening** should be performed **at least annually** for adults aged 40 and older, or more frequently if there are risk factors.
- Screening only every 3 years is insufficient for a 46-year-old patient.
*Yearly Pap smear*
- **Pap smear frequency** has changed; for women aged 30-65 with normal results, screening is recommended every **3 years** with cytology alone, or every 5 years with high-risk HPV testing alone or co-testing.
- A yearly Pap smear is no longer typical practice for a woman with normal prior results and no specific risk factors.
*Bone mineral density screening*
- **Bone mineral density (BMD) screening** for osteoporosis is typically recommended for women starting at age **65 years** or earlier if they have significant risk factors.
- This patient is 46 years old and has no mentioned risk factors, so BMD screening is not routinely indicated at this age.
Carrier screening for genetic disorders US Medical PG Question 7: A 28-year-old G2P1 female is concerned that she may give birth to another child with Down syndrome. She states that she may not be able to take care of another child with this disorder. Which of the following tests can confirm the diagnosis of Down syndrome in utero?
- A. Ultrasound
- B. Triple marker test
- C. Integrated test
- D. Quadruple marker test
- E. Amniocentesis (Correct Answer)
Carrier screening for genetic disorders Explanation: ***Amniocentesis***
- **Amniocentesis** is a **diagnostic procedure** that involves collecting amniotic fluid to obtain fetal cells for **karyotyping**, which can definitively confirm the presence of an extra chromosome 21, the cause of Down syndrome.
- This test is typically performed between **15 and 20 weeks of gestation** and carries a small risk of complication but offers conclusive results.
*Ultrasound*
- **Ultrasound** is a **screening tool** that can detect anatomical features suggestive of Down syndrome, such as **nuchal translucency** or heart defects, but it cannot definitively diagnose the condition.
- It identifies **markers** that increase the suspicion of Down syndrome, prompting further diagnostic testing, but does not provide genetic confirmation.
*Triple marker test*
- The **triple marker test** is a **screening test** that measures levels of **alpha-fetoprotein (AFP)**, **unconjugated estriol (uE3)**, and **human chorionic gonadotropin (hCG)** in maternal blood.
- While it can estimate the risk of Down syndrome, it is not a diagnostic test and only provides a **risk assessment**, not a definitive diagnosis.
*Integrated test*
- The **integrated test** combines results from first-trimester screening (nuchal translucency and PAPP-A) and second-trimester screening (quadruple marker test) to provide a **single risk assessment**.
- Like other screening tests, it calculates a **risk probability** for Down syndrome but does not offer a definitive diagnosis.
*Quadruple marker test*
- The **quadruple marker test** measures AFP, uE3, hCG, and **inhibin A** in maternal blood during the second trimester.
- It is a **screening test** used to assess the risk of Down syndrome and open neural tube defects, but it is not a diagnostic tool.
Carrier screening for genetic disorders US Medical PG Question 8: A 34-year-old gravida 2 para 1 woman at 16 weeks gestation presents for prenatal care. Her prenatal course has been uncomplicated. She takes no medications besides her prenatal vitamin which she takes every day, and she has been compliant with routine prenatal care. She has a 7-year-old daughter who is healthy. The results of her recent quadruple screen are listed below:
AFP: Low
hCG: Low
Estriol: Low
Inhibin-A: Normal
Which of the following is the most appropriate next step to confirm the diagnosis?
- A. Chorionic villus sampling
- B. Amniocentesis (Correct Answer)
- C. Ultrasound for nuchal translucency
- D. Folic acid supplementation
- E. Return to clinic in 4 weeks
Carrier screening for genetic disorders Explanation: ***Amniocentesis***
- The presented quad screen results (low AFP, low hCG, low estriol, normal Inhibin-A) are highly suggestive of **trisomy 18 (Edwards syndrome)**. Amniocentesis is a **definitive diagnostic test** that can confirm aneuploidy by providing a fetal karyotype.
- While typically performed between **15 and 20 weeks gestation**, it can differentiate between trisomy 18 and trisomy 21 (Down syndrome), which usually presents with high hCG and high Inhibin-A.
*Chorionic villus sampling (CVS)*
- **CVS** is typically performed earlier in pregnancy, between **10 and 13 weeks gestation**, meaning it is too late to perform at 16 weeks gestation.
- While it can provide a fetal karyotype for genetic diagnosis, the gestational age presented in the vignette makes this option currently inappropriate.
*Ultrasound for nuchal translucency*
- **Nuchal translucency (NT)** is part of the first-trimester screening, usually measured between **11 and 14 weeks gestation**.
- At 16 weeks gestation, measuring NT would be **outside the appropriate timeframe**, and the second-trimester quad screen has already been completed, making further screening rather than diagnosis less useful.
*Folic acid supplementation*
- **Folic acid supplementation** is crucial before and during early pregnancy to prevent neural tube defects, which would be associated with high AFP.
- The patient is already taking prenatal vitamins (which contain folic acid), and her quad screen results are not indicative of a neural tube defect but rather a chromosomal abnormality.
*Return to clinic in 4 weeks*
- The abnormal quad screen results indicate a **high risk for aneuploidy**, specifically trisomy 18, which requires immediate follow-up and definitive diagnosis.
- Delaying further assessment for 4 weeks would be clinically inappropriate and could increase patient anxiety and potentially reduce options for further management.
Carrier screening for genetic disorders US Medical PG Question 9: A 25-year-old man with a genetic disorder presents for genetic counseling because he is concerned about the risk that any children he has will have the same disease as himself. Specifically, since childhood he has had difficulty breathing requiring bronchodilators, inhaled corticosteroids, and chest physiotherapy. He has also had diarrhea and malabsorption requiring enzyme replacement therapy. If his wife comes from a population where 1 in 10,000 people are affected by this same disorder, which of the following best represents the likelihood a child would be affected as well?
- A. 0.01%
- B. 2%
- C. 0.5%
- D. 1% (Correct Answer)
- E. 50%
Carrier screening for genetic disorders Explanation: ***Correct Option: 1%***
- The patient's symptoms (difficulty breathing requiring bronchodilators, inhaled corticosteroids, and chest physiotherapy; diarrhea and malabsorption requiring enzyme replacement therapy) are classic for **cystic fibrosis (CF)**, an **autosomal recessive disorder**.
- For an autosomal recessive disorder with a prevalence of 1 in 10,000 in the general population, **q² = 1/10,000**, so **q = 1/100 = 0.01**. The carrier frequency **(2pq)** is approximately **2q = 2 × (1/100) = 1/50 = 0.02**.
- The affected man is **homozygous recessive (aa)** and will always pass on the recessive allele. His wife has a **1/50 chance of being a carrier (Aa)**. If she is a carrier, she has a **1/2 chance of passing on the recessive allele**.
- Therefore, the probability of an affected child = **(Probability wife is a carrier) × (Probability wife passes recessive allele) = 1/50 × 1/2 = 1/100 = 1%**.
*Incorrect Option: 0.01%*
- This percentage is too low and does not correctly account for the carrier frequency in the population and the probability of transmission from a carrier mother.
*Incorrect Option: 2%*
- This represents approximately the carrier frequency (1/50 ≈ 2%), but does not account for the additional 1/2 probability that a carrier mother would pass on the recessive allele.
*Incorrect Option: 0.5%*
- This value would be correct if the carrier frequency were 1/100 instead of 1/50, which does not match the given population prevalence.
*Incorrect Option: 50%*
- **50%** would be the risk if both parents were carriers of an autosomal recessive disorder (1/4 chance = 25% for affected, but if we know one parent passes the allele, conditional probability changes). More accurately, 50% would apply if the disorder were **autosomal dominant** with one affected parent, which is not the case here.
Carrier screening for genetic disorders US Medical PG Question 10: A 46-year-old man presents with increasing fatigue and weakness for the past 3 months. He works as a lawyer and is handling a complicated criminal case which is very stressful, and he attributes his fatigue to his work. He lost 2.3 kg (5.0 lb) during this time despite no change in diet or activity level. His past history is significant for chronic constipation and infrequent episodes of bloody stools. Family history is significant for his father and paternal uncle who died of colon cancer and who were both known to possess a genetic mutation for the disease. He has never had a colonoscopy or had any genetic testing performed. Physical examination is significant for conjunctival pallor. A colonoscopy is performed and reveals few adenomatous polyps. Histopathologic examination shows high-grade dysplasia and genetic testing reveals the same mutation as his father and uncle. The patient is concerned about his 20-year-old son. Which of the following is the most appropriate advice regarding this patient's son?
- A. The son doesn't need to be tested now.
- B. An immediate colonoscopy should be ordered for the son.
- C. Screening can be started by 50 years of age as the son’s risk is similar to the general population.
- D. The son should undergo a prophylactic colonic resection.
- E. A genetic test followed by colonoscopy for the son should be ordered. (Correct Answer)
Carrier screening for genetic disorders Explanation: ***A genetic test followed by colonoscopy for the son should be ordered.***
- Given the patient's strong family history of **colon cancer** with a known genetic mutation and the patient's own diagnosis of **high-grade dysplasia** and the same mutation, his son is at a significantly increased risk.
- **Genetic testing** will determine if the son has inherited the mutation, and if positive, early and regular **colonoscopic surveillance** is crucial due to the highly aggressive nature of familial colon cancer syndromes.
*The son doesn't need to be tested now.*
- This statement is incorrect because the son is at a very high risk of inheriting a **known pathogenic genetic mutation** that predisposes to colon cancer.
- Delaying testing could lead to a delayed diagnosis of potentially cancerous or pre-cancerous lesions, missing the opportunity for **early intervention**.
*An immediate colonoscopy should be ordered for the son.*
- While a colonoscopy may be warranted, the initial step should be **genetic testing** to confirm the presence of the mutation.
- If the genetic test is negative, the urgency and frequency of colonoscopies would be different, potentially aligning with general population guidelines or slightly earlier, but not necessarily immediately at age 20 without genetic confirmation.
*Screening can be started by 50 years of age as the son’s risk is similar to the general population.*
- This advice is dangerously incorrect, as the son's risk is *not* similar to the general population due to a strong and **documented family history** of colon cancer with a **known genetic mutation**.
- Waiting until 50 years of age would likely result in delayed detection of advanced adenomas or even cancer, as familial syndromes typically present at a much **younger age**.
*The son should undergo a prophylactic colonic resection.*
- **Prophylactic colonic resection** is a major surgical procedure and is typically reserved for individuals with established diagnoses of certain high-risk syndromes, such as **Familial Adenomatous Polyposis (FAP)**, often after they have developed numerous polyps.
- This decision should only be made after **genetic confirmation** of the mutation, thorough evaluation of polyp burden, and shared decision-making with the patient and multidisciplinary team, and not as an initial step.
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