Genetic Counseling and Risk Assessment — MCQs

10 questions

A 25-year-old man presents for a routine examination and is found to have an early diastolic murmur on examination. Clinical findings suggest hypertrophic cardiomyopathy. The family pedigree shows affected individuals in three consecutive generations with both males and females affected, and no generation is skipped. What is the most likely mode of inheritance of this genetic condition?

Which of the following is least commonly associated with Down's syndrome?

Differential expression of the same gene depending on parent of origin is referred to as

Which of the following conditions is least likely to be inherited in a familial manner?

Which of the following represents the current recommendation for offering screening for Down's syndrome during pregnancy?

24 yr old mother with 7 week POG presents to ANC OPD with accidental low-dose radiation exposure. What is the most appropriate immediate management?

Molecular genetic testing is used to detect all of the following except?

What is the most common genetic abnormality in cystic fibrosis?

HNPCC has defect in which

Q10

In amyloidosis, beta pleated sheets can be directly visualized at the molecular level using:

Genetic Counseling and Risk Assessment Indian Medical PG Practice Questions and MCQs

Question 1: A 25-year-old man presents for a routine examination and is found to have an early diastolic murmur on examination. Clinical findings suggest hypertrophic cardiomyopathy. The family pedigree shows affected individuals in three consecutive generations with both males and females affected, and no generation is skipped. What is the most likely mode of inheritance of this genetic condition?

A. AD (Correct Answer)
B. AR
C. XLD
D. XLR

Explanation: ***AD (Autosomal Dominant)*** - The presence of affected individuals in **three consecutive generations** without skipping generations is a hallmark of autosomal dominant inheritance [1]. - Both **males and females are affected** equally, indicating it is not X-linked [1]. *AR (Autosomal Recessive)* - **Autosomal recessive** conditions typically **skip generations** and affect siblings, as carriers can pass on the gene without expressing the disease. - Such conditions often show a **25% recurrence risk** in offspring of two carrier parents, which is not suggested here. *XLD (X-linked Dominant)* - **X-linked dominant** inheritance would show **affected fathers passing the trait to all their daughters** but none of their sons, which is not specified. - Affected mothers would have a **50% chance** of passing the trait to each child, regardless of sex. *XLR (X-linked Recessive)* - **X-linked recessive** conditions predominantly affect **males**, and affected fathers cannot pass the trait to their sons. - Females are typically carriers, and affected males often have unaffected parents, which would imply skipping generations.

Question 2: Which of the following is least commonly associated with Down's syndrome?

A. Periodontal disease
B. Delayed eruption of deciduous teeth
C. Premature loss of deciduous teeth (Correct Answer)
D. Retrognathia

Explanation: ***Premature loss of deciduous teeth*** - **Premature loss of deciduous teeth** is the **least commonly associated** feature with Down syndrome among the given options. - While individuals with Down syndrome have increased periodontal disease that can lead to tooth loss, **premature exfoliation of deciduous teeth as a primary developmental feature is uncommon**. - Tooth loss, when it occurs, is typically a **secondary consequence** of severe periodontal destruction rather than an intrinsic developmental anomaly causing premature shedding. - Unlike the delayed eruption pattern which is a consistent finding, premature loss is not a characteristic feature of Down syndrome itself. *Delayed eruption of deciduous teeth* - This is a **common characteristic** of Down syndrome, not the least common. - Infants with Down syndrome frequently experience **delayed eruption of both deciduous and permanent teeth**, reflecting the generalized slower maturation seen in this condition. - Dental developmental delay is well-documented and consistently observed. *Periodontal disease* - This is **very common** in Down syndrome, with prevalence rates of 58-96%. - Individuals have significantly **increased prevalence and severity of periodontal disease** due to compromised immune function, poor oral hygiene, and specific anatomical factors. - One of the most consistent oral manifestations of Down syndrome. *Retrognathia* - **Retrognathia** (recessed lower jaw) is a **common craniofacial feature** in Down syndrome. - Contributes to difficulties in feeding, speech, and can impact airway patency. - Part of the characteristic facial phenotype.

Question 3: Differential expression of the same gene depending on parent of origin is referred to as

A. Mosaicism
B. Nonpenetrance
C. Anticipation
D. Genomic imprinting (Correct Answer)

Explanation: ***Genomic imprinting*** - This phenomenon describes the differential expression of a gene based on its **parent of origin**, meaning that the gene is expressed only from the allele inherited from a specific parent (either maternal or paternal). - This differential expression occurs without altering the underlying DNA sequence and is often mediated by **epigenetic mechanisms** such as DNA methylation. *Mosaicism* - This refers to the presence of **two or more populations of cells** with different genotypes within a single individual who has developed from a single fertilized egg. - It does not involve differential expression of the same gene based on parental origin, but rather **genetic differences arising after fertilization**. *Nonpenetrance* - **Nonpenetrance** describes a situation where an individual carries a disease-causing gene mutation but **does not express the associated phenotype** or clinical symptoms. - This concept explains variability in disease manifestation, not differential gene expression based on parental origin. *Anticipation* - **Anticipation** is a phenomenon in genetic disorders where the symptoms become **more severe** and/or appear at an **earlier age** in successive generations. - This is often seen in disorders caused by expansion of trinucleotide repeats, such as Huntington's disease, and is not related to parent-of-origin gene expression.

Question 4: Which of the following conditions is least likely to be inherited in a familial manner?

A. Factor V Leiden mutation (Correct Answer)
B. Hemophilia
C. Sickle cell anemia
D. Acquired thrombotic thrombocytopenic purpura (TTP)

Explanation: ***Thalassemia*** - Thalassemia is a **genetic blood disorder** caused by mutations in hemoglobin genes [1], but biomarkers for diagnosis can sometimes arise **de novo**. - It exhibits **incomplete penetrance** and variable expressivity, meaning not all family members may express the trait despite sharing genes. *Hemophilia* - Hemophilia is a **X-linked recessive** disorder predominantly affecting males, passed from carrier mothers to sons [2]. - The condition leads to **deficiencies in blood clotting factors**, which are inherited in a recognizable familial pattern, though about 30% of patients have no family history due to new mutations [2]. *Factor V Leiden mutation* - Factor V Leiden is an **autosomal dominant** genetic mutation leading to increased clotting risk, often inherited from affected parents. - It presents as a familial tendency towards **venous thromboembolism**, clearly identifying its transmission. *Sickle cell anemia* - Sickle cell anemia is an **autosomal recessive** disorder, requiring two copies of the mutated gene for expression, commonly inherited within families [1]. - It leads to characteristic **sickle-shaped red blood cells**, with a clear familial pattern of inheritance [1]. It is important to distinguish that **hereditary disorders** are by definition transmitted through generations and are therefore **familial**.

Question 5: Which of the following represents the current recommendation for offering screening for Down's syndrome during pregnancy?

A. 35
B. No screening necessary
C. 30
D. All in the reproductive age group (Correct Answer)

Explanation: ***All in the reproductive age group*** - The American College of Obstetricians and Gynecologists (ACOG) and other major medical bodies recommend that **all pregnant women**, regardless of age, be offered **screening for Down syndrome** and other aneuploidies. - This recommendation reflects the principle of **patient autonomy** and the availability of safe and effective screening methods for all pregnancies, not just those considered high-risk based on maternal age. *30* - While the risk of Down syndrome increases with maternal age, **screening is not exclusively recommended for women aged 30**; rather, it is offered to all pregnant women. - Focusing only on this age group would **miss cases** in younger women and limit informed decision-making. *35* - Historically, **maternal age 35** was considered the threshold for offering invasive diagnostic testing due to the significantly increased risk of Down syndrome. - However, current guidelines emphasize universal screening, as a substantial number of babies with Down syndrome are born to women **younger than 35** due to higher birth rates in this group. *No screening necessary* - This option is incorrect as **screening is routinely offered** to all pregnant women to provide information about the risk of conditions like Down syndrome. - Deciding to forgo screening or diagnostic testing is a personal choice, but the **option to screen should always be available** to the patient.

Question 6: 24 yr old mother with 7 week POG presents to ANC OPD with accidental low-dose radiation exposure. What is the most appropriate immediate management?

A. Reassure and continue pregnancy (Correct Answer)
B. Perform detailed fetal anomaly scan
C. Advise medical termination of pregnancy
D. Advise genetic counseling and testing

Explanation: ***Reassure and continue pregnancy*** - **Low-dose radiation exposure** (typically defined as <50 mGy) during pregnancy is generally associated with a very low risk of fetal anomalies or adverse outcomes. The patient should be reassured that the risk to the fetus is minimal. - The threshold for concern for teratogenic effects from radiation is significantly higher than a low dose, and **medical termination of pregnancy** is not indicated in such cases. - This is the most appropriate **immediate management** for accidental low-dose radiation exposure at 7 weeks gestation. *Perform detailed fetal anomaly scan* - While anomaly scans are part of routine prenatal care, performing an immediate, detailed scan solely due to **low-dose radiation exposure** at 7 weeks is not the most appropriate *immediate* management. The risk of anomalies from such exposure is extremely low and unlikely to be detectable at 7 weeks. - A more detailed scan may be considered at later gestational ages (e.g., 18-20 weeks) as part of standard care, but not as an emergency response to low-dose exposure. *Advise medical termination of pregnancy* - Medical termination is **not indicated** for accidental **low-dose radiation exposure**. Termination is only considered in cases of *extremely high* and confirmed doses (e.g., >100 mGy), which carry a significant risk of severe fetal anomalies or mortality. - Such high doses are rare in accidental exposures and would necessitate a thorough dose assessment by a radiation physicist before considering any drastic measures. - Since the scenario specifies low-dose exposure, termination would be inappropriate and potentially harmful counseling. *Advise genetic counseling and testing* - **Genetic counseling** and testing would be indicated for known genetic risks, advanced maternal age, or suspicion of chromosomal abnormalities, none of which are suggested by accidental **low-dose radiation exposure**. - Radiation-induced effects are typically teratogenic rather than directly causing inheritable genetic mutations that would be detected by standard genetic testing.

Question 7: Molecular genetic testing is used to detect all of the following except?

A. Deletion
B. Translocation (Correct Answer)
C. Amplification
D. Point mutation

Explanation: ***Translocation*** - **Translocations** are chromosomal rearrangements that were historically detected primarily by **cytogenetic methods** (karyotyping, conventional FISH), rather than by traditional molecular genetic testing methods focused on DNA sequencing [3]. - While modern molecular techniques like **RT-PCR for fusion transcripts** (e.g., BCR-ABL), **NGS-based fusion detection**, and **targeted breakpoint sequencing** can now detect translocations, the classic distinction is that translocations involve large-scale structural chromosomal changes better visualized by cytogenetics [2], [3]. - In the traditional classification, molecular genetic testing referred primarily to **sequence-based methods** (PCR, Sanger sequencing) that detect smaller-scale DNA changes rather than gross chromosomal rearrangements. *Deletion* - **Deletions** are readily detected by molecular genetic testing using PCR, Sanger sequencing, MLPA (Multiplex Ligation-dependent Probe Amplification), and NGS [5]. - These techniques identify missing DNA sequences by analyzing changes in fragment size, read depth, or absence of expected amplification products [2], [5]. *Amplification* - **Amplification** (increased gene copy number) is detected by molecular methods including **quantitative PCR (qPCR)**, **digital PCR**, and **NGS-based copy number analysis** [4]. - These techniques quantify gene copy numbers to identify amplifications like HER2 amplification in breast cancer. *Point mutation* - **Point mutations** are the primary target of classic molecular genetic testing [1]. - Detected by **Sanger sequencing**, **allele-specific PCR**, **NGS panels**, and other sequence-based methods that identify single nucleotide changes in DNA [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 185. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-186. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 342-343. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 344. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 183-184.

Question 8: What is the most common genetic abnormality in cystic fibrosis?

A. ΔF508 (Correct Answer)
B. R117H
C. G551D
D. G542X

Explanation: ***ΔF508*** - This mutation accounts for approximately **70% of all cystic fibrosis (CF) cases** worldwide, making it the most common genetic abnormality [1]. - It results in the deletion of a **phenylalanine residue** at position 508 in the **CFTR protein**, leading to misfolding and degradation [1]. *R117H mutation* - This is a rare **splice-site mutation** that can cause a milder form of CF or CFTR-related disorders. - It results in reduced CFTR protein function but is not the most common mutation. *G551D mutation* - This mutation is a **class III gating mutation**, meaning it impairs the opening of the **chloride channel** rather than its synthesis or trafficking. - It is relatively rare and is specifically targeted by CFTR modulator therapies like ivacaftor. *G542X mutation* - This is a **class I nonsense mutation** that introduces a premature stop codon, leading to a truncated and non-functional CFTR protein [1]. - While it causes severe CF, it is less common than the ΔF508 mutation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, p. 476.

Question 9: HNPCC has defect in which

A. Mismatch repair gene (Correct Answer)
B. Base excision repair
C. Point mutation
D. Nucleotide excision repair

Explanation: ***Mismatch repair gene*** - **HNPCC (hereditary non-polyposis colorectal cancer)**, also known as Lynch syndrome, is caused by inherited mutations in genes responsible for **DNA mismatch repair** [1]. - These genes, such as **MLH1, MSH2, MSH6, and PMS2**, normally correct errors that occur during DNA replication, preventing the accumulation of mutations. *Base pair excision* - **Base excision repair** is a distinct DNA repair pathway that primarily fixes small base lesions, such as damaged or modified bases. - This mechanism is not primarily implicated in the development of HNPCC. *Point mutation* - A **point mutation** refers to a single nucleotide change in a DNA sequence, which can be the *result* of a defective repair mechanism but is not the defect itself. - While mismatch repair defects lead to an increased rate of point mutations, the underlying *defect* in HNPCC is in the repair system, not in the mutation type. *Nucleotide excision* - **Nucleotide excision repair** is a major pathway for removing bulky, helix-distorting DNA lesions, such as those caused by UV radiation. - Defects in this pathway are associated with conditions like **xeroderma pigmentosum**, not HNPCC. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, p. 817.

Question 10: In amyloidosis, beta pleated sheets can be directly visualized at the molecular level using:

A. Electron microscope
B. X-ray crystallography (Correct Answer)
C. Congo red stain
D. Cryo-electron microscopy

Explanation: ***Congo red stain*** - Congo red stain is **specific** for detecting amyloid deposits, showing a characteristic **apple-green birefringence** under polarized light [1]. - The presence of **beta-pleated sheets** is a key feature of the amyloid fibrils that this stain highlights, confirming amyloidosis [1]. *Spiral electron microscope* - The **spiral electron microscope** is not a standard technique used for identifying amyloid structures or deposits. - It does not provide the **specificity** required to visualize amyloid-related beta-pleated sheets. *Electron microscope* - While electron microscopy can visualize amyloid fibrils [2], it does not specifically confirm the **beta-pleated sheet** structure like Congo red does. - This technique requires more complex preparations and does not have the same **ease of interpretation** for diagnosing amyloidosis. *X-ray crystallography* - X-ray crystallography is primarily used to determine the **three-dimensional** structure of crystalline substances, not specific to amyloid detection. - It does not provide direct evidence of **amyloid deposits** like Congo red staining does. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 268-269. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 135-136.

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