Genetic Basis of Developmental Disorders — MCQs
What is the relationship between maternal age and the risk of having a child with Down syndrome?
Which one of the following is an autosomal recessive disorder?
An affected male does not have affected children but an affected female always has affected children. Type of inheritance?
What is the genotype of Klinefelter syndrome?
Kinky hair disease is a disorder where an affected child has peculiar white stubby hair, does not grow, brain degeneration is seen and dies by age of two years. Mrs A is hesitant about having children because her two sisters had sons who died from kinky hair disease. Her mother's brother also died of the same condition. Which of the following is the possible mode of inheritance in her family?
Which of the following is the MOST accurate test for detecting neural tube defects?
Which of the following is a characteristic feature of Down syndrome?
18 weeks pregnant female presents with no high risk of NTD and low risk of trisomy 21 on quad test. What is the most appropriate next step in management?
Wilson's disease has which of the following inheritance?
A patient presents with headache, confusion, and a diagnosis of a brain tumor. The family history reveals brain and kidney tumors. What is the most likely diagnosis?
Genetic Basis of Developmental Disorders Indian Medical PG Practice Questions and MCQs
Question 1: What is the relationship between maternal age and the risk of having a child with Down syndrome?
- A. Is not influenced by maternal age
- B. Decreases with increasing maternal age
- C. Increases with increasing paternal age
- D. Increases with increasing maternal age (Correct Answer)
Explanation: ***Increases with increasing maternal age*** - The risk of having a child with **Down syndrome (Trisomy 21)** significantly **increases with advanced maternal age**, particularly after 35 years. - This is primarily due to the increased likelihood of **nondisjunction during meiosis I** in older oocytes. *Is not influenced by maternal age* - This statement is incorrect as there is a well-established and **strong correlation** between advanced maternal age and the incidence of chromosomal abnormalities. - Epidemiological studies consistently show a **rising curve** of Down syndrome risk with increasing maternal age. *Decreases with increasing maternal age* - This is the opposite of the observed epidemiological and biological reality for Down syndrome. - The risk actually **exponentially increases** as the mother ages beyond 35 years. *Increases with increasing paternal age* - While advanced paternal age is associated with an increased risk of some **single-gene dominant disorders** (e.g., achondroplasia, Marfan syndrome), its contribution to Down syndrome risk is minor compared to maternal age. - **Paternal age** has a much weaker and less consistent association with aneuploidies like Down syndrome.
Question 2: Which one of the following is an autosomal recessive disorder?
- A. Albinism (Correct Answer)
- B. Marfan’s syndrome
- C. Neurofibromatosis-1
- D. Huntington's disease
Explanation: ***Albinism*** - **Albinism** is an **autosomal recessive disorder** characterized by a partial or complete lack of melanin pigment in the skin, hair, and eyes [1], [2]. - This condition is inherited when an individual receives **two copies of the defective gene**, one from each parent [1]. *Huntington's disease* - **Huntington's disease** is an **autosomal dominant disorder**, meaning only one copy of the mutated gene is sufficient to cause the disease. - It is characterized by progressive neurodegeneration, leading to uncontrolled movements, cognitive decline, and psychiatric problems. *Marfan's syndrome* - **Marfan's syndrome** is an **autosomal dominant disorder** affecting connective tissue, primarily impacting the skeletal, ocular, and cardiovascular systems. - It results from a mutation in the **FBN1 gene** which encodes for fibrillin-1, a component of elastic fibers. *Neurofibromatosis-1* - **Neurofibromatosis type 1 (NF1)** is an **autosomal dominant disorder** caused by a mutation in the NF1 gene, leading to the growth of tumors along nerves. - Clinical features include **café-au-lait spots**, neurofibromas, and Lisch nodules. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 150-151. [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. 119-120.
Question 3: An affected male does not have affected children but an affected female always has affected children. Type of inheritance?
- A. Autosomal recessive
- B. Mitochondrial (Correct Answer)
- C. X linked recessive
- D. X linked dominant
Explanation: ***Correct Option: Mitochondrial*** - This pattern describes **mitochondrial inheritance**, where all children of an **affected mother** inherit the condition because mitochondria are exclusively inherited from the ovum (maternal inheritance). - An **affected father** cannot pass on the condition to his children, as sperm contribute only nuclear DNA and essentially no mitochondria. - This is the **only inheritance pattern** where an affected male has no affected children while an affected female has all children affected. *Incorrect Option: Autosomal recessive* - This pattern would typically show affected individuals having unaffected parents (who are carriers) and both males and females being affected in equal proportions. - It does not explain the complete absence of transmission from an affected father or universal transmission from an affected mother. - An affected individual could have unaffected children if their partner is not a carrier. *Incorrect Option: X linked recessive* - In **X-linked recessive inheritance**, affected males cannot pass the trait to their sons, but all their daughters would be carriers (not affected). - An affected mother would pass the trait to all her sons (affected) and make all her daughters carriers (not affected), which does not match the described pattern of all children being affected. *Incorrect Option: X linked dominant* - In **X-linked dominant inheritance**, an affected father passes the trait to all his daughters but none of his sons (contradicts "no affected children"). - An affected mother has a 50% chance of passing the trait to **each child**, which is inconsistent with all children of an affected female being affected.
Question 4: What is the genotype of Klinefelter syndrome?
- A. 47,XXY (Correct Answer)
- B. Trisomy 13
- C. 47,XXX
- D. 45,X
Explanation: ***47,XXY*** - This genotype represents the presence of an **extra X chromosome** in males, which is the defining characteristic of Klinefelter syndrome. - Individuals with this syndrome typically have **47 chromosomes** instead of the usual 46. *45,X* - This genotype describes **Turner syndrome**, which is characterized by the absence of one X chromosome in females [1]. - Individuals with Turner syndrome are typically female and present with a distinct set of physical features and health issues. *47,XXX* - This genotype is known as **Triple X syndrome** or **Trisomy X**, which affects females who have an extra X chromosome. - While it involves an extra sex chromosome, it is distinct from Klinefelter syndrome both in terms of affected sex and clinical presentation. *Trisomy 13* - This refers to **Patau syndrome**, a severe chromosomal disorder caused by an extra copy of chromosome 13. - It is an **autosomal trisomy** and is not related to sex chromosome abnormalities like Klinefelter syndrome. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 191-192.
Question 5: Kinky hair disease is a disorder where an affected child has peculiar white stubby hair, does not grow, brain degeneration is seen and dies by age of two years. Mrs A is hesitant about having children because her two sisters had sons who died from kinky hair disease. Her mother's brother also died of the same condition. Which of the following is the possible mode of inheritance in her family?
- A. X-linked recessive (Correct Answer)
- B. Autosomal dominant
- C. X-linked dominant
- D. Autosomal recessive
Explanation: ***X-linked recessive*** - Kinky hair disease (Menkes disease) is an **X-linked recessive disorder**, meaning that males are predominantly affected, and females are carriers. - The pattern of inheritance in the family (sons of sisters, and a maternal uncle affected) is highly suggestive of **X-linked recessive inheritance**, as healthy female carriers can pass the gene to their sons. *Autosomal dominant* - In **autosomal dominant** inheritance, the disease would affect individuals in every generation, and both males and females would be affected equally. - This pattern of inheritance does not explain why only sons are dying and why sisters (who are likely carriers) are unaffected but have affected children. *X-linked dominant* - In **X-linked dominant** inheritance, affected fathers would pass the trait to all their daughters, and affected mothers would pass it to half of their children. - The disease would also be more common in females, which contradicts the described pattern of only sons being affected and dying. *Autosomal recessive* - In **autosomal recessive** inheritance, both parents must be carriers for a child to be affected, and typically, there would be a 25% chance of recurrence in each pregnancy. - This mode doesn't explain the observation of affected maternal uncles and sons from sisters, which points more directly to an X-linked pattern where females are carriers.
Question 6: Which of the following is the MOST accurate test for detecting neural tube defects?
- A. USG (Correct Answer)
- B. Placentography
- C. Chromosomal analysis
- D. Amniocentesis
Explanation: ***USG (Ultrasound)*** - **High-resolution ultrasound** is the **gold standard and most accurate imaging modality** for detecting **neural tube defects (NTDs)** due to its ability to directly visualize anatomical structures of the fetus. - **Diagnostic accuracy**: Detection rate >95% for anencephaly and 80-90% for open spina bifida with targeted anomaly scan at 18-20 weeks. - Can identify specific features such as **lemon sign** (frontal bone scalloping), **banana sign** (cerebellar compression), direct visualization of **spina bifida**, **anencephaly**, or **encephalocele**. - **Non-invasive, safe, and widely available**, making it the primary diagnostic tool in clinical practice. *Amniocentesis* - **Amniocentesis** measures **alpha-fetoprotein (AFP)** and **acetylcholinesterase (AChE)** in amniotic fluid, which are elevated in open NTDs. - While highly accurate as a **confirmatory test** (near 99% sensitivity with both markers), it is **invasive** with risk of miscarriage (0.1-0.3%). - Used primarily when ultrasound findings are **equivocal** or for **biochemical confirmation**, not as the first-line diagnostic test. - In modern practice, ultrasound has largely replaced amniocentesis for NTD diagnosis due to superior imaging technology. *Chromosomal analysis* - **Chromosomal analysis** (karyotyping) detects **chromosomal abnormalities** like trisomies (Down syndrome, Edwards syndrome). - NTDs are **structural malformations**, not chromosomal abnormalities, though some chromosomal disorders may have associated structural defects. - Does not directly diagnose NTDs. *Placentography* - **Placentography** is used to localize the **placenta** in cases of suspected **placenta previa** or for guiding invasive procedures. - Provides no information about **fetal anatomy** and is not used for detecting NTDs.
Question 7: Which of the following is a characteristic feature of Down syndrome?
- A. Trisomy 18
- B. Robertsonian translocation involving chromosome 21
- C. Trisomy 21 (Correct Answer)
- D. Trisomy 13
Explanation: ***Trisomy 21*** - **Down syndrome** is the most common autosomal chromosome abnormality and is characterized by the presence of an extra copy of chromosome 21 [1, 2]. - This extra genetic material leads to the characteristic physical features, intellectual disability, and medical conditions associated with the syndrome [1, 2]. *Trisomy 18* - **Trisomy 18**, also known as **Edwards syndrome**, is a serious chromosomal disorder distinct from Down syndrome [2]. - It is characterized by severe developmental problems, including **heart defects**, **kidney malformations**, and **severe intellectual disability**, with generally a much shorter life expectancy [2, 3]. *Robertsonian translocation involving chromosome 21* - A **Robertsonian translocation** involving chromosome 21 is a cause of Down syndrome, but it is not the characteristic feature itself; rather, it is a specific **chromosomal rearrangement** that can lead to an extra copy of chromosome 21 material [1, 2]. - This specific type of translocation accounts for only a small percentage (2-3%) of all Down syndrome cases, while **Trisomy 21** (nondisjunction) is the most common cause [1, 2]. *Trisomy 13* - **Trisomy 13**, also known as **Patau syndrome**, is a distinct chromosomal disorder characterized by the presence of an extra copy of chromosome 13 [2]. - It is associated with severe birth defects, including **cleft lip/palate**, **polydactyly**, and severe neurological problems, and is usually fatal within the first year of life [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 170-171. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 171-172. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169.
Question 8: 18 weeks pregnant female presents with no high risk of NTD and low risk of trisomy 21 on quad test. What is the most appropriate next step in management?
- A. Repeat non-invasive screening test.
- B. Perform invasive diagnostic testing.
- C. Perform amniotic fluid analysis.
- D. Perform a detailed fetal ultrasound. (Correct Answer)
Explanation: ***Perform a detailed fetal ultrasound.*** - A **detailed fetal ultrasound** (often referred to as an **anatomy scan**) at around 18-22 weeks is a standard component of prenatal care for all pregnant women, regardless of screening test results. - This ultrasound evaluates fetal anatomy for structural anomalies, assesses fetal growth, and confirms gestational age, providing crucial information even with low-risk screening. *Repeat non-invasive screening test.* - Repeating a non-invasive screening test (like another quad screen or NIPT) is generally **not indicated** when initial results show a low risk and there are no other clinical concerns. - Such tests are primarily for screening purposes, and a second low-risk result would offer little additional actionable information, as their positive predictive value is low. *Perform invasive diagnostic testing.* - **Invasive diagnostic testing**, such as **amniocentesis** or **chorionic villus sampling (CVS)**, carries a risk of miscarriage and is reserved for situations with a high risk of chromosomal abnormalities or genetic conditions. - Given the low-risk quad screen results for trisomy 21 and no high risk for NTDs, invasive testing is **not warranted** at this stage. *Perform amniotic fluid analysis.* - **Amniotic fluid analysis** is part of an amniocentesis, an **invasive diagnostic procedure** designed to detect chromosomal abnormalities or genetic disorders. - This procedure is typically reserved for cases where screening tests indicate a high risk or there is a clinical suspicion of a genetic condition; it's **not a routine step** after a low-risk quad screen.
Question 9: Wilson's disease has which of the following inheritance?
- A. It is an acquired disease
- B. Autosomal recessive (Correct Answer)
- C. X-linked recessive
- D. Autosomal dominant
Explanation: ***Autosomal recessive*** - Wilson's disease is caused by mutations in the **ATP7B gene**, which codes for a copper-transporting ATPase. - For an individual to develop the disease, they must inherit **two copies of the mutated gene**, one from each parent. *It is an acquired disease* - Wilson's disease is a **genetic disorder**, meaning it is inherited, not acquired through environmental factors or lifestyle [1]. - While symptoms may manifest later in life, the underlying cause is a **predisposing genetic mutation** [1]. *X-linked recessive* - X-linked recessive disorders primarily affect males as they have only one X chromosome; however, Wilson's disease **affects both sexes equally**. - The gene responsible for Wilson's disease, **ATP7B**, is located on **chromosome 13**, an autosome, not on the X chromosome. *Autosomal dominant* - In autosomal dominant inheritance, only **one copy of the mutated gene** is sufficient to cause the disease, and it is usually seen in every generation. - Wilson's disease requires **two mutated copies** of the gene to manifest, and carriers (heterozygotes) are typically asymptomatic.
Question 10: A patient presents with headache, confusion, and a diagnosis of a brain tumor. The family history reveals brain and kidney tumors. What is the most likely diagnosis?
- A. Neurofibromatosis
- B. Li-Fraumeni syndrome
- C. VHL syndrome (Correct Answer)
- D. Churg-Strauss syndrome
Explanation: ***VHL syndrome*** - **Von Hippel-Lindau (VHL) syndrome** is an inherited disorder characterized by the growth of tumors and cysts in various parts of the body, including the **brain (hemangioblastomas)** and **kidneys (renal cell carcinoma)**. - The presentation of a brain tumor, kidney tumors, and a positive family history for both organs strongly points to VHL syndrome. *Neurofibromatosis* - **Neurofibromatosis (NF)** typically presents with **cafe-au-lait spots**, neurofibromas, optic gliomas, and Lisch nodules. - While it involves brain tumors, kidney tumors are not a primary feature of NF. *Li-Fraumeni syndrome* - **Li-Fraumeni syndrome** is associated with an increased risk of various cancers, including **sarcomas**, **breast cancer**, **adrenocortical carcinomas**, and **leukemia**. - While brain tumors can occur, the specific combination of brain and kidney tumors with a clear family history is less characteristic of Li-Fraumeni than VHL syndrome. *Churg-Strauss syndrome* - **Churg-Strauss syndrome (Eosinophilic Granulomatosis with Polyangiitis)** is a systemic vasculitis characterized by **asthma**, **eosinophilia**, and **granulomatous inflammation**. - It does not involve the development of brain or kidney tumors.
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