Multifactorial Inheritance Disorders — MCQs
Which of the following disorders is most commonly associated with multifactorial inheritance?
The risk of recurrence of congenital heart disease for subsequent pregnancies in families with one affected child is:
The commonest mode of inheritance of congenital heart disease is
Risk of genetic diseases in consanguineous marriage between first cousins?
Which one of the following is an autosomal dominant disorder?
A researcher wants to determine whether there is an association between CRP values and the risk of MI or cancer. Four relative risk (RR) values were plotted $(0.5,1.5,1.7,1.8)$ with respect to CRP levels. What conclusion can be drawn?
What is the chance of a child having cystic fibrosis if both parents are carriers of the disease?
Neonate is brought at 3 weeks of age, with projectile vomiting. USG was performed and is shown below. When can the abdominal mass in this condition be best palpated?
An infant brought to the clinic with non-bilious projectile vomiting. The investigation of choice includes:
Identify the congenital defect seen in this baby.
Multifactorial Inheritance Disorders US Medical PG Practice Questions and MCQs
Question 1: Which of the following disorders is most commonly associated with multifactorial inheritance?
- A. Achondroplasia
- B. Lysosomal storage disease
- C. Cleft lip (Correct Answer)
- D. Huntington disease
Explanation: ***Cleft lip*** - **Cleft lip** is a classic example of a **multifactorial disorder**, resulting from the interaction of multiple genes and environmental factors. - Its recurrence risk is typically observed to be around 2-5% in affected families, consistent with **multifactorial inheritance**. *Achondroplasia* - Achondroplasia is an **autosomal dominant disorder**, caused by a single gene mutation in the **FGFR3 gene**. - It does not primarily involve the complex interplay of multiple genes and environmental factors characteristic of multifactorial inheritance. *Lysosomal storage disease* - Lysosomal storage diseases are a group of **autosomal recessive disorders**, each caused by a defect in a specific lysosomal enzyme. - They follow classic **Mendelian inheritance patterns** rather than multifactorial models. *Huntington disease* - Huntington disease is an **autosomal dominant neurodegenerative disorder**, caused by a trinucleotide repeat expansion in the **HTT gene**. - It exhibits a clear dominant inheritance pattern and does not involve multiple genes or significant environmental contributions in its etiology.
Question 2: The risk of recurrence of congenital heart disease for subsequent pregnancies in families with one affected child is:
- A. 10-12%
- B. 1%
- C. 2-6% (Correct Answer)
- D. 0.80%
Explanation: ***2-6%*** - The recurrence risk for **congenital heart disease (CHD)** in subsequent pregnancies after one affected child is generally cited as **2-6%**, reflecting an increased familial predisposition. - This risk is higher than the general population risk but still relatively low, primarily due to the complex, multifactorial etiology of most CHDs. *10-12%* - A **10-12% recurrence risk** is generally too high for most common congenital heart defects, which are typically multifactorial. - Such a high risk might be seen in specific **syndromic forms** of CHD (e.g., genetic aneuploidies or single gene defects), but not for isolated CHD in general. *1%* - A **1% recurrence risk** is comparable to the general population incidence of congenital heart disease (approximately 0.8-1%). - This value does not adequately reflect the established **increased risk for siblings** of an affected child, which is known to be higher than the background population risk. *0.80%* - **0.80%** represents the approximate **general population incidence** of congenital heart disease in live births without a prior affected sibling. - This figure does not account for the **increased familial risk** that exists once one child in a family is already affected.
Question 3: The commonest mode of inheritance of congenital heart disease is
- A. Autosomal recessive
- B. Multifactorial (Correct Answer)
- C. Sex-linked dominant
- D. Autosomal dominant
Explanation: ***Multifactorial*** - **Congenital heart disease (CHD)** is primarily caused by a combination of genetic predispositions and environmental factors [1]. - This **multifactorial inheritance** means that while genes play a role in susceptibility, specific environmental triggers during fetal development are also crucial [1], [4]. *Autosomal recessive* - This mode of inheritance is associated with conditions that only manifest if an individual inherits two copies of a **mutated gene**, one from each parent. - While some rare forms of CHD can be autosomal recessive, it is not the most common inheritance pattern for the majority of cases. *Sex-linked dominant* - **Sex-linked dominant** disorders are caused by mutations on the X chromosome and affect males and females differently, with affected fathers passing the trait to all their daughters but no sons. - This pattern is not typically observed as the primary mode of inheritance for general CHD. *Autosomal dominant* - In **autosomal dominant inheritance**, only one copy of an altered gene is needed for the condition to manifest [2]. - While certain syndromes associated with CHD can be autosomal dominant (e.g., Marfan syndrome), it is not the most frequent mode of inheritance for isolated CHD [3].
Question 4: Risk of genetic diseases in consanguineous marriage between first cousins?
- A. 1-2%
- B. 4-8% (Correct Answer)
- C. 8-10%
- D. 12-14%
- E. 2-4%
Explanation: ***4-8%*** - The risk of genetic diseases in offspring from a **first-cousin consanguineous marriage** is generally estimated to be **two- to threefold higher than the baseline risk** in the general population. - While the general population risk for a serious birth defect or genetic disease is around 3-4%, this increased risk typically places the range for first cousins at **4-8%**. *1-2%* - This percentage represents a **lower risk than what is typically observed** with first-cousin consanguinity. - The baseline risk for genetic disease in the general population is usually around 3-4%, and consanguineous unions significantly increase this risk. *2-4%* - This represents approximately the **baseline population risk** without consanguinity, not the increased risk seen with first-cousin marriages. - Students may incorrectly assume that first-cousin marriage does not significantly elevate the baseline genetic disease risk. *8-10%* - While there is an increased risk, this range is generally considered **higher than the average estimated risk** for first-cousin consanguineous marriages, which is typically quoted at 4-8%. - This higher range might be seen in cases of **more distant consanguinity** or in populations with a **higher prevalence of specific recessive conditions**. *12-14%* - This magnitude of risk is usually associated with **closer degrees of consanguinity**, such as uncle-niece or half-sibling relationships, rather than first cousins. - The **coefficient of inbreeding** for first cousins is 1/16, which carries a lower risk than these closer relationships.
Question 5: Which one of the following is an autosomal dominant disorder?
- A. Cystic fibrosis
- B. Hereditary spherocytosis (Correct Answer)
- C. Sickle cell anemia
- D. G-6PD deficiency
Explanation: ***Hereditary spherocytosis*** - It is characterized by **autosomal dominant inheritance** [1], leading to the destruction of red blood cells. - Mutations in proteins that maintain the **red blood cell membrane** integrity result in spherocyte formation [1]. *Cystic fibrosis* - This condition follows a **autosomal recessive inheritance pattern**, requiring two copies of the mutated gene for disease manifestation. - It is caused by mutations in the **CFTR gene**, affecting chloride transport and leading to thick secretions. *G-6PD deficiency* - This disorder is inherited in an **X-linked recessive manner** [2], primarily affecting males and transmitted through carrier females. - Characterized by **hemolytic anemia** triggered by certain medications or infections, it does not follow dominant inheritance [2]. *Sickle cell anemia* - Sickle cell anemia is also an **autosomal recessive disorder** [3], meaning affected individuals must inherit two copies of the sickle cell gene. - It results in a mutation in the **HBB gene**, leading to the production of abnormal hemoglobin (HbS) [3].
Question 6: A researcher wants to determine whether there is an association between CRP values and the risk of MI or cancer. Four relative risk (RR) values were plotted $(0.5,1.5,1.7,1.8)$ with respect to CRP levels. What conclusion can be drawn?
- A. CRP has no relationship
- B. CRP decreases & disease decreases
- C. CRP increases disease/cancer risk (Correct Answer)
- D. No association in first interval
- E. CRP shows protective effect in first interval
Explanation: ***CRP increases disease/cancer risk*** - A **relative risk (RR)** greater than 1 indicates an increased risk of the outcome (MI or cancer) in the exposed group (higher CRP levels) compared to the unexposed group. - The plots show RRs of 1.5, 1.7, and 1.8, all of which are greater than 1, consistently indicating that higher CRP levels are associated with an elevated risk for MI or cancer. - The overall trend across the four intervals demonstrates a positive association between CRP and disease risk. *CRP has no relationship* - This conclusion is incorrect because three of the four plotted RR values (1.5, 1.7, 1.8) are above 1, indicating a positive association or increased risk. - An RR of 1 signifies no relationship, but the majority of values clearly deviate from 1, showing a definite association. *CRP decreases & disease decreases* - While one RR value (0.5) suggests a decreased risk, the majority of the given RRs (1.5, 1.7, 1.8) are greater than 1, indicating an increased risk. - This option would only be true if all or most RR values were less than 1, implying a protective effect, which is not the overall trend here. *No association in first interval* - The first interval shows an RR of 0.5. An RR of 1 indicates no association, while an RR of 0.5 actually indicates a **decreased risk or protective effect**, rather than no association. - Therefore, stating "no association" for the first interval is inaccurate given the definition of relative risk. *CRP shows protective effect in first interval* - While the first interval RR of 0.5 does suggest a protective effect in isolation, this option fails to capture the **overall conclusion** from all four data points. - When interpreting multiple RR values together, the predominant pattern (three values >1) indicates an overall increased risk, making this a misleading conclusion for the study as a whole.
Question 7: What is the chance of a child having cystic fibrosis if both parents are carriers of the disease?
- A. 75%
- B. 25% (Correct Answer)
- C. 50%
- D. 0%
- E. 100%
Explanation: ***50%*** - If one parent is affected by cystic fibrosis (CF), they are **homozygous for the CFTR mutation**, while the normal parent is likely **homozygous for the normal allele**. - Each child has a **50% chance** of inheriting the **mutated allele** from the affected parent, resulting in an **autosomal recessive** inheritance pattern [1]. *70%* - This percentage does not reflect the inheritance probabilities associated with **autosomal recessive traits** [1], such as cystic fibrosis. - In heterozygous and normal arrangements, the calculation does not support a **70%** inheritance chance of the disease. *80%* - Similarly, an **80% chance** is inaccurate as cystic fibrosis requires two mutated alleles for the disease to manifest [1]. - The inheritance pattern does not allow for a higher than **50% chance** when one parent is normal. *25%* - A **25% chance** applies if both parents were carriers of the CFTR mutation [1]. However, with only one affected parent, this percentage does not apply. - The maximum **chance of inheritance** from one affected and one normal parent is accurately stated as **50%**. **References:** [1] 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. 53-54.
Question 8: Neonate is brought at 3 weeks of age, with projectile vomiting. USG was performed and is shown below. When can the abdominal mass in this condition be best palpated?
- A. During feeding (Correct Answer)
- B. In umbilical area
- C. In epigastric area
- D. In Right upper quadrant
Explanation: ***During feeding*** - In **hypertrophic pyloric stenosis**, the characteristic **"olive" mass** formed by the thickened pylorus is most easily palpable **during feeding or immediately after vomiting**. - During this time, the infant’s abdominal muscles are relaxed, making palpation of the mass in the **epigastrium (right upper quadrant)** more successful. *In umbilical area* - The umbilical area is typically where **omphaloceles** or **umbilical hernias** are found, not the pyloric mass. - The pylorus is located much higher in the epigastric region, to the right of the midline. *In epigastric area* - While the pyloric mass is located in the **epigastric area**, palpation is more difficult when the infant is crying or agitated. - The question asks when it can be *best* palpated, emphasizing the conditions under which it is most detectable. *In Right upper quadrant* - The pylorus is indeed located in the **right upper quadrant/epigastrium**. - However, the optimal timing for palpation is during feeding or after vomiting, as the infant's abdomen is relaxed at that point.
Question 9: An infant brought to the clinic with non-bilious projectile vomiting. The investigation of choice includes:
- A. Sigmoidoscopy
- B. Abdominal ultrasonography (Correct Answer)
- C. Barium meal
- D. Flexible Endoscopy
Explanation: ***Abdominal ultrasonography*** - **Abdominal ultrasonography** is the **investigation of choice** for **hypertrophic pyloric stenosis** presenting with non-bilious projectile vomiting in infants. - It is **non-invasive**, avoids **radiation exposure**, and has high sensitivity and specificity (>95%). - USG demonstrates a **thickened pyloric muscle** (>3 mm), **elongated pyloric channel** (>15-17 mm), and **absent or reduced passage of gastric contents** through the pylorus. - The characteristic **"target sign"** or **"doughnut sign"** on transverse view and **"cervix sign"** on longitudinal view are diagnostic. *Barium meal* - A **barium meal** (upper GI series) can demonstrate the characteristic **"string sign"** or **"shoulder sign"** in pyloric stenosis, showing a narrowed pyloric channel. - However, it is **not the first-line investigation** due to **radiation exposure**, being more time-consuming, and less practical in sick infants. - It may be used when **USG is inconclusive** or unavailable, but has been largely replaced by ultrasound in modern practice. *Flexible Endoscopy* - **Flexible endoscopy** is an **invasive procedure** and is not the first-line diagnostic tool for pyloric stenosis in infants. - It may be considered in atypical cases to rule out other diagnoses like **gastroesophageal reflux disease (GERD)**, **esophagitis**, or **gastritis**. *Sigmoidoscopy* - **Sigmoidoscopy** examines the **lower gastrointestinal tract** (sigmoid colon and rectum) and is completely **irrelevant** to the diagnosis of non-bilious projectile vomiting. - This presentation indicates an **upper GI pathology** (pyloric stenosis), not a lower GI condition. - Sigmoidoscopy is used for conditions like **inflammatory bowel disease** or **rectal bleeding**.
Question 10: Identify the congenital defect seen in this baby.
- A. Craniorachischisis totalis (Correct Answer)
- B. Cystic hygroma
- C. Cervical meningocele
- D. Encephalocele
Explanation: ***Craniorachischisis totalis*** - This is a severe form of **neural tube defect** characterized by complete failure of closure of the neural tube, involving both the **cranial and spinal regions**. - The image shows an extensive defect affecting the entire length of the neural axis, with exposed brain tissue and spinal cord, which is consistent with **craniorachischisis totalis**. *Cystic hygroma* - A **cystic hygroma** is a congenital malformation of the lymphatic system, typically appearing as a multicystic mass, most commonly in the **neck or axilla**. - It does not involve exposed brain or spinal cord tissue and has a different appearance than the extensive defect shown in the image. *Cervical meningocele* - A **cervical meningocele** is a type of spina bifida where only the **meninges** (membranes surrounding the spinal cord) protrude through a defect in the cervical spine. - While it involves the spine, it is usually a localized sac-like protrusion, and the brain itself is not extensively exposed as seen in the image. *Encephalocele* - An **encephalocele** is a neural tube defect where there is a protrusion of brain tissue and/or meninges through an opening in the **skull**, typically at the back of the head. - While it involves the brain, it is generally a localized defect of the skull, not extending the entire length of the spine and cranium as depicted in the image.
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