FMF CGE Exam Questions and Answers - 300
Practice Questions with Solutions Newest Complete
Questions And Correct Detailed Answers| Already
Graded A+
1. A 30-year-old woman with a history of recurrent early pregnancy losses undergoes cytogenetic
analysis of products of conception. The karyotype shows a balanced translocation between
chromosomes 2 and 5, with breakpoints at 2q21 and 5p15.1. Which of the following is the most
likely mechanism leading to her recurrent miscarriages?
A. Unbalanced segregation during meiosis I producing gametes with partial trisomy and monosomy
B. Maternal age-related nondisjunction causing aneuploidy in the embryo
C. Imprinting defects due to disruption of imprinted genes at the breakpoints
D. Uniparental disomy for chromosome 2 or 5 resulting from trisomy rescue
Answer: A
Rationale: Balanced translocation carriers are at risk of producing unbalanced gametes due to alternate,
adjacent-1, or adjacent-2 segregation during meiosis. Unbalanced segregation leads to partial trisomy
and monosomy, which are usually lethal and cause early miscarriages. Nondisjunction (B) is not directly
related to the translocation. Imprinting defects (C) are less likely unless breakpoints disrupt imprinted
regions, but the main mechanism is segregation. Uniparental disomy (D) is rare and not the primary
cause.
2. A 45-year-old man is diagnosed with familial adenomatous polyposis (FAP) and undergoes
genetic testing. A heterozygous germline pathogenic variant in the APC gene is identified. His
25-year-old daughter, who is asymptomatic, requests predictive testing. She is counseled that if she
inherits the variant, her lifetime risk of colorectal cancer is approximately 90%, and prophylactic
colectomy is recommended. Which of the following ethical principles is most directly challenged
when considering the daughter's request for testing?
A. Beneficence, because the test may cause psychological harm without clear medical benefit
B. Nonmaleficence, because the test results could lead to discrimination by insurers
C. Autonomy, because the daughter has the right to make an informed decision about testing
D. Justice, because the test is expensive and may not be equally accessible
Answer: A
Rationale: Predictive testing for FAP in an asymptomatic adult offers clear medical benefit (surveillance
and prophylactic surgery), so beneficence is not challenged; rather, the principle of nonmaleficence is
relevant because of potential psychological harm and discrimination, but the most direct challenge is to
autonomy (C) as the daughter has the right to choose. However, the question asks which is 'most directly
challenged'-the daughter's autonomy is respected, so it is not challenged. The correct answer is A
because the test may cause anxiety and stigma, but since medical benefit exists, beneficence is not truly
violated. Actually, the best answer is C, because the daughter's autonomy is challenged if the provider
Page 1
,refuses testing. Let me re-evaluate: The scenario describes that she is counseled and recommended
colectomy if positive. The ethical challenge is that her autonomy may be overridden if she is pressured to
test or if results are used against her will. However, the principle most challenged is beneficence because
the test may cause harm without clear benefit? No, benefit is clear. I think the intended answer is C, but
the explanation must justify. Given typical ethics questions, the correct answer is C because autonomy is
the right to choose, which must be respected.
3. A 28-year-old woman undergoes first-trimester combined screening for aneuploidy. Nuchal
translucency (NT) is 3.5 mm (99th percentile for crown-rump length), PAPP-A is 0.3 MoM, and
free -hCG is 2.5 MoM. The calculated risk for trisomy 21 is 1:10. She declines invasive testing. At
20 weeks, ultrasound reveals a ventricular septal defect, echogenic intracardiac focus, and a sandal
gap. Which of the following additional findings is most likely to be present?
A. Absent nasal bone
B. Single umbilical artery
C. Choroid plexus cyst
D. Echogenic bowel
Answer: A
Rationale: The combination of increased NT, low PAPP-A, high ²-hCG, and soft markers (VSD, EIF,
sandal gap) is highly suspicious for trisomy 21. Absent nasal bone is another soft marker for trisomy 21,
commonly seen in the second trimester. Single umbilical artery (B) is associated with trisomy 18, as are
choroid plexus cysts (C) and echogenic bowel (D) (though echogenic bowel can also be seen in trisomy
21, but less specific). The most specific additional marker for trisomy 21 among the options is absent
nasal bone.
4. A couple with a history of a child affected by cystic fibrosis (CF) presents for prenatal diagnosis.
The mother is a known carrier of the F508del mutation, and the father's carrier status is unknown.
The father undergoes expanded carrier screening and is found to have a heterozygous pathogenic
variant in the CFTR gene, but it is a different mutation (G551D). The couple is counseled that the
fetus has a 1 in 4 chance of being affected. However, the fetus is found to have compound
heterozygosity for F508del and G551D. Which of the following best describes the expected
phenotype?
A. Classic CF with pancreatic insufficiency and progressive lung disease
B. Mild CF with pancreatic sufficiency and later onset of respiratory symptoms
C. CFTR-related disorder with congenital bilateral absence of the vas deferens
D. No clinical disease because G551D is a benign variant
Answer: A
Rationale: F508del is a severe mutation causing class II defect, and G551D is a class III gating mutation.
Compound heterozygotes for these two mutations typically have classic CF with pancreatic insufficiency
and severe lung disease, though G551D is associated with some residual function and may be milder
than F508del homozygotes. However, the combination still leads to classic CF. Mild CF (B) is more
typical for mutations with residual function (e.g., R117H). CBAVD (C) is seen in men with CFTR
mutations but without classic CF. G551D is pathogenic, not benign (D).
Page 2
,5. A 32-year-old woman with a family history of breast cancer undergoes genetic testing for
hereditary cancer syndromes. She is found to have a deletion encompassing exons 1-2 of the
BRCA1 gene. Which of the following mechanisms is most likely to have generated this deletion?
A. Non-allelic homologous recombination (NAHR) between Alu repeats
B. Non-homologous end joining (NHEJ) after a double-strand break
C. Nucleotide excision repair (NER) malfunction
D. Mismatch repair (MMR) deficiency leading to microsatellite instability
Answer: A
Rationale: Large genomic deletions in BRCA1 are often mediated by NAHR between Alu repeats, which
are abundant in the BRCA1 region. NHEJ (B) typically causes small insertions/deletions, not large
deletions. NER (C) repairs bulky DNA adducts, not double-strand breaks. MMR deficiency (D) leads to
microsatellite instability, not large deletions.
6. A 38-year-old woman undergoes amniocentesis at 16 weeks for advanced maternal age. The
karyotype is 46,XX, but array comparative genomic hybridization (aCGH) reveals a 1.2 Mb
duplication at 15q11.2 encompassing the TUBGCP5, CYFIP1, NIPA2, and NIPA1 genes. The
parents are phenotypically normal and their aCGH results are normal. Which of the following is
the most appropriate interpretation and counseling?
A. This is a benign variant; no further action is needed
B. This is a variant of uncertain significance; parental testing is recommended
C. This is a pathogenic duplication associated with autism and intellectual disability
D. This duplication is likely pathogenic and indicates a risk for Prader-Willi syndrome
Answer: B
Rationale: The 15q11.2 BP1-BP2 duplication (Burnside-Butler syndrome) is a known susceptibility locus
for neurodevelopmental disorders, but it is not fully penetrant and is often inherited from unaffected
parents. Given normal parental arrays, the duplication is de novo, but its clinical significance is
uncertain because it may be a low-penetrance risk factor. Thus, it is a variant of uncertain significance
(VUS). It is not benign (A) because it has been associated with phenotypes. It is not definitively
pathogenic (C) because many carriers are normal. It is not Prader-Willi (D) which involves deletion of
15q11.2-q13.
7. A 29-year-old woman with a body mass index (BMI) of 32 kg/m² undergoes first-trimester
screening. Her nuchal translucency is 1.8 mm (50th percentile), and serum markers are PAPP-A
0.45 MoM and free -hCG 1.8 MoM. The calculated risk for trisomy 21 is 1:200. She is counseled
about noninvasive prenatal testing (NIPT). Which of the following factors is most likely to affect
the accuracy of NIPT in this patient?
A. Maternal obesity reduces the fetal fraction, increasing the risk of test failure
B. Low PAPP-A indicates placental dysfunction, leading to false-positive results
C. Increased BMI alters the kinetics of cell-free DNA, causing false negatives
D. The presence of a vanishing twin could lead to discordant results
Answer: A
Rationale: Maternal obesity is associated with lower fetal fraction due to dilution of cell-free fetal DNA
by maternal DNA, which can lead to test failure or false-negative results. Low PAPP-A (B) is not directly
related to NIPT accuracy. Increased BMI does not alter kinetics (C) but reduces fetal fraction. Vanishing
Page 3
, twin (D) can cause false positives, but the question asks for the most likely factor affecting accuracy;
obesity is a known confounder.
8. A 35-year-old woman with a history of a child with a neural tube defect (NTD) is planning a
pregnancy. She is currently taking a multivitamin containing 400 mcg of folic acid. Which of the
following is the most appropriate recommendation to reduce the risk of NTD recurrence?
A. Increase folic acid supplementation to 4 mg daily, starting at least 1 month before conception and continuing
through the first trimester
B. Continue current multivitamin and add a separate folic acid supplement of 400 mcg
C. Switch to a prenatal vitamin with 800 mcg folic acid and add a daily serving of folate-rich foods
D. Prescribe a high-dose folic acid of 5 mg daily only after a positive pregnancy test
Answer: A
Rationale: For women with a previous NTD, the recommended dose is 4 mg (4000 mcg) of folic acid
daily, starting at least 1 month before conception and continuing through the first 12 weeks of
pregnancy. This is based on evidence that high-dose folic acid reduces recurrence risk. Option B (800
mcg total) is insufficient. Option D is too late, as neural tube closure occurs by day 28 post-conception.
9. A 40-year-old woman presents for genetic counseling after receiving a positive NIPT result for
monosomy X (45,X). Confirmatory amniocentesis reveals a mosaic karyotype: 45,X[20]/46,XX[10].
Which of the following is the most likely clinical outcome?
A. Typical Turner syndrome with short stature, webbed neck, and ovarian failure
B. Mild or no phenotypic abnormalities, depending on the distribution of the 46,XX cell line
C. Male phenotype with ambiguous genitalia due to Y chromosome material
D. High risk for neurodevelopmental delay and congenital heart defects
Answer: B
Rationale: Mosaicism for 45,X/46,XX often results in a milder phenotype or even normal phenotype if the
normal cell line is predominant in critical tissues. Many women with this mosaicism are fertile and have
few Turner stigmata. Typical Turner syndrome (A) is more common with non-mosaic 45,X. Male
phenotype (C) requires Y chromosome material. Neurodevelopmental delay (D) is not typical for Turner
mosaicism.
10. A 27-year-old woman undergoes chorionic villus sampling (CVS) at 11 weeks for a family
history of Duchenne muscular dystrophy (DMD). The fetal DNA analysis shows a deletion of exons
45-50 in the DMD gene. The mother is a known carrier of the same deletion. Which of the
following is the most appropriate next step in management?
A. Offer termination of pregnancy because the fetus is male and will be affected
B. Perform fetal muscle biopsy to confirm the diagnosis
C. Determine fetal sex by karyotype; if female, she will be a carrier but unaffected
D. Recommend prenatal corticosteroid therapy to delay disease onset
Answer: C
Rationale: DMD is X-linked; a male fetus with a deletion will be affected, but a female fetus with one
deletion is a carrier and usually asymptomatic. Since the deletion is known, the first step is to determine
fetal sex. If female, the child will be a carrier but not affected, and termination is not necessary. Option
A is premature without sex determination. Muscle biopsy (B) is invasive and not needed. Corticosteroids
Page 4
Practice Questions with Solutions Newest Complete
Questions And Correct Detailed Answers| Already
Graded A+
1. A 30-year-old woman with a history of recurrent early pregnancy losses undergoes cytogenetic
analysis of products of conception. The karyotype shows a balanced translocation between
chromosomes 2 and 5, with breakpoints at 2q21 and 5p15.1. Which of the following is the most
likely mechanism leading to her recurrent miscarriages?
A. Unbalanced segregation during meiosis I producing gametes with partial trisomy and monosomy
B. Maternal age-related nondisjunction causing aneuploidy in the embryo
C. Imprinting defects due to disruption of imprinted genes at the breakpoints
D. Uniparental disomy for chromosome 2 or 5 resulting from trisomy rescue
Answer: A
Rationale: Balanced translocation carriers are at risk of producing unbalanced gametes due to alternate,
adjacent-1, or adjacent-2 segregation during meiosis. Unbalanced segregation leads to partial trisomy
and monosomy, which are usually lethal and cause early miscarriages. Nondisjunction (B) is not directly
related to the translocation. Imprinting defects (C) are less likely unless breakpoints disrupt imprinted
regions, but the main mechanism is segregation. Uniparental disomy (D) is rare and not the primary
cause.
2. A 45-year-old man is diagnosed with familial adenomatous polyposis (FAP) and undergoes
genetic testing. A heterozygous germline pathogenic variant in the APC gene is identified. His
25-year-old daughter, who is asymptomatic, requests predictive testing. She is counseled that if she
inherits the variant, her lifetime risk of colorectal cancer is approximately 90%, and prophylactic
colectomy is recommended. Which of the following ethical principles is most directly challenged
when considering the daughter's request for testing?
A. Beneficence, because the test may cause psychological harm without clear medical benefit
B. Nonmaleficence, because the test results could lead to discrimination by insurers
C. Autonomy, because the daughter has the right to make an informed decision about testing
D. Justice, because the test is expensive and may not be equally accessible
Answer: A
Rationale: Predictive testing for FAP in an asymptomatic adult offers clear medical benefit (surveillance
and prophylactic surgery), so beneficence is not challenged; rather, the principle of nonmaleficence is
relevant because of potential psychological harm and discrimination, but the most direct challenge is to
autonomy (C) as the daughter has the right to choose. However, the question asks which is 'most directly
challenged'-the daughter's autonomy is respected, so it is not challenged. The correct answer is A
because the test may cause anxiety and stigma, but since medical benefit exists, beneficence is not truly
violated. Actually, the best answer is C, because the daughter's autonomy is challenged if the provider
Page 1
,refuses testing. Let me re-evaluate: The scenario describes that she is counseled and recommended
colectomy if positive. The ethical challenge is that her autonomy may be overridden if she is pressured to
test or if results are used against her will. However, the principle most challenged is beneficence because
the test may cause harm without clear benefit? No, benefit is clear. I think the intended answer is C, but
the explanation must justify. Given typical ethics questions, the correct answer is C because autonomy is
the right to choose, which must be respected.
3. A 28-year-old woman undergoes first-trimester combined screening for aneuploidy. Nuchal
translucency (NT) is 3.5 mm (99th percentile for crown-rump length), PAPP-A is 0.3 MoM, and
free -hCG is 2.5 MoM. The calculated risk for trisomy 21 is 1:10. She declines invasive testing. At
20 weeks, ultrasound reveals a ventricular septal defect, echogenic intracardiac focus, and a sandal
gap. Which of the following additional findings is most likely to be present?
A. Absent nasal bone
B. Single umbilical artery
C. Choroid plexus cyst
D. Echogenic bowel
Answer: A
Rationale: The combination of increased NT, low PAPP-A, high ²-hCG, and soft markers (VSD, EIF,
sandal gap) is highly suspicious for trisomy 21. Absent nasal bone is another soft marker for trisomy 21,
commonly seen in the second trimester. Single umbilical artery (B) is associated with trisomy 18, as are
choroid plexus cysts (C) and echogenic bowel (D) (though echogenic bowel can also be seen in trisomy
21, but less specific). The most specific additional marker for trisomy 21 among the options is absent
nasal bone.
4. A couple with a history of a child affected by cystic fibrosis (CF) presents for prenatal diagnosis.
The mother is a known carrier of the F508del mutation, and the father's carrier status is unknown.
The father undergoes expanded carrier screening and is found to have a heterozygous pathogenic
variant in the CFTR gene, but it is a different mutation (G551D). The couple is counseled that the
fetus has a 1 in 4 chance of being affected. However, the fetus is found to have compound
heterozygosity for F508del and G551D. Which of the following best describes the expected
phenotype?
A. Classic CF with pancreatic insufficiency and progressive lung disease
B. Mild CF with pancreatic sufficiency and later onset of respiratory symptoms
C. CFTR-related disorder with congenital bilateral absence of the vas deferens
D. No clinical disease because G551D is a benign variant
Answer: A
Rationale: F508del is a severe mutation causing class II defect, and G551D is a class III gating mutation.
Compound heterozygotes for these two mutations typically have classic CF with pancreatic insufficiency
and severe lung disease, though G551D is associated with some residual function and may be milder
than F508del homozygotes. However, the combination still leads to classic CF. Mild CF (B) is more
typical for mutations with residual function (e.g., R117H). CBAVD (C) is seen in men with CFTR
mutations but without classic CF. G551D is pathogenic, not benign (D).
Page 2
,5. A 32-year-old woman with a family history of breast cancer undergoes genetic testing for
hereditary cancer syndromes. She is found to have a deletion encompassing exons 1-2 of the
BRCA1 gene. Which of the following mechanisms is most likely to have generated this deletion?
A. Non-allelic homologous recombination (NAHR) between Alu repeats
B. Non-homologous end joining (NHEJ) after a double-strand break
C. Nucleotide excision repair (NER) malfunction
D. Mismatch repair (MMR) deficiency leading to microsatellite instability
Answer: A
Rationale: Large genomic deletions in BRCA1 are often mediated by NAHR between Alu repeats, which
are abundant in the BRCA1 region. NHEJ (B) typically causes small insertions/deletions, not large
deletions. NER (C) repairs bulky DNA adducts, not double-strand breaks. MMR deficiency (D) leads to
microsatellite instability, not large deletions.
6. A 38-year-old woman undergoes amniocentesis at 16 weeks for advanced maternal age. The
karyotype is 46,XX, but array comparative genomic hybridization (aCGH) reveals a 1.2 Mb
duplication at 15q11.2 encompassing the TUBGCP5, CYFIP1, NIPA2, and NIPA1 genes. The
parents are phenotypically normal and their aCGH results are normal. Which of the following is
the most appropriate interpretation and counseling?
A. This is a benign variant; no further action is needed
B. This is a variant of uncertain significance; parental testing is recommended
C. This is a pathogenic duplication associated with autism and intellectual disability
D. This duplication is likely pathogenic and indicates a risk for Prader-Willi syndrome
Answer: B
Rationale: The 15q11.2 BP1-BP2 duplication (Burnside-Butler syndrome) is a known susceptibility locus
for neurodevelopmental disorders, but it is not fully penetrant and is often inherited from unaffected
parents. Given normal parental arrays, the duplication is de novo, but its clinical significance is
uncertain because it may be a low-penetrance risk factor. Thus, it is a variant of uncertain significance
(VUS). It is not benign (A) because it has been associated with phenotypes. It is not definitively
pathogenic (C) because many carriers are normal. It is not Prader-Willi (D) which involves deletion of
15q11.2-q13.
7. A 29-year-old woman with a body mass index (BMI) of 32 kg/m² undergoes first-trimester
screening. Her nuchal translucency is 1.8 mm (50th percentile), and serum markers are PAPP-A
0.45 MoM and free -hCG 1.8 MoM. The calculated risk for trisomy 21 is 1:200. She is counseled
about noninvasive prenatal testing (NIPT). Which of the following factors is most likely to affect
the accuracy of NIPT in this patient?
A. Maternal obesity reduces the fetal fraction, increasing the risk of test failure
B. Low PAPP-A indicates placental dysfunction, leading to false-positive results
C. Increased BMI alters the kinetics of cell-free DNA, causing false negatives
D. The presence of a vanishing twin could lead to discordant results
Answer: A
Rationale: Maternal obesity is associated with lower fetal fraction due to dilution of cell-free fetal DNA
by maternal DNA, which can lead to test failure or false-negative results. Low PAPP-A (B) is not directly
related to NIPT accuracy. Increased BMI does not alter kinetics (C) but reduces fetal fraction. Vanishing
Page 3
, twin (D) can cause false positives, but the question asks for the most likely factor affecting accuracy;
obesity is a known confounder.
8. A 35-year-old woman with a history of a child with a neural tube defect (NTD) is planning a
pregnancy. She is currently taking a multivitamin containing 400 mcg of folic acid. Which of the
following is the most appropriate recommendation to reduce the risk of NTD recurrence?
A. Increase folic acid supplementation to 4 mg daily, starting at least 1 month before conception and continuing
through the first trimester
B. Continue current multivitamin and add a separate folic acid supplement of 400 mcg
C. Switch to a prenatal vitamin with 800 mcg folic acid and add a daily serving of folate-rich foods
D. Prescribe a high-dose folic acid of 5 mg daily only after a positive pregnancy test
Answer: A
Rationale: For women with a previous NTD, the recommended dose is 4 mg (4000 mcg) of folic acid
daily, starting at least 1 month before conception and continuing through the first 12 weeks of
pregnancy. This is based on evidence that high-dose folic acid reduces recurrence risk. Option B (800
mcg total) is insufficient. Option D is too late, as neural tube closure occurs by day 28 post-conception.
9. A 40-year-old woman presents for genetic counseling after receiving a positive NIPT result for
monosomy X (45,X). Confirmatory amniocentesis reveals a mosaic karyotype: 45,X[20]/46,XX[10].
Which of the following is the most likely clinical outcome?
A. Typical Turner syndrome with short stature, webbed neck, and ovarian failure
B. Mild or no phenotypic abnormalities, depending on the distribution of the 46,XX cell line
C. Male phenotype with ambiguous genitalia due to Y chromosome material
D. High risk for neurodevelopmental delay and congenital heart defects
Answer: B
Rationale: Mosaicism for 45,X/46,XX often results in a milder phenotype or even normal phenotype if the
normal cell line is predominant in critical tissues. Many women with this mosaicism are fertile and have
few Turner stigmata. Typical Turner syndrome (A) is more common with non-mosaic 45,X. Male
phenotype (C) requires Y chromosome material. Neurodevelopmental delay (D) is not typical for Turner
mosaicism.
10. A 27-year-old woman undergoes chorionic villus sampling (CVS) at 11 weeks for a family
history of Duchenne muscular dystrophy (DMD). The fetal DNA analysis shows a deletion of exons
45-50 in the DMD gene. The mother is a known carrier of the same deletion. Which of the
following is the most appropriate next step in management?
A. Offer termination of pregnancy because the fetus is male and will be affected
B. Perform fetal muscle biopsy to confirm the diagnosis
C. Determine fetal sex by karyotype; if female, she will be a carrier but unaffected
D. Recommend prenatal corticosteroid therapy to delay disease onset
Answer: C
Rationale: DMD is X-linked; a male fetus with a deletion will be affected, but a female fetus with one
deletion is a carrier and usually asymptomatic. Since the deletion is known, the first step is to determine
fetal sex. If female, the child will be a carrier but not affected, and termination is not necessary. Option
A is premature without sex determination. Muscle biopsy (B) is invasive and not needed. Corticosteroids
Page 4
