Genetics and Disease — MCQs

Genetics and Disease Indian Medical PG Practice Questions and MCQs

Question 21: Which of the following is NOT a feature of Marfan's syndrome?

A. Arachnodactyly
B. Reduced joint mobility (Correct Answer)
C. Dislocation of the lens
D. Mitral regurgitation

Explanation: Marfan’s syndrome is an autosomal dominant connective tissue disorder caused by a mutation in the **FBN1 gene** on chromosome 15, which encodes **fibrillin-1**. Fibrillin-1 is essential for the structural integrity of the extracellular matrix and the regulation of TGF-β. **Why "Reduced joint mobility" is the correct answer:** In Marfan’s syndrome, the defect in fibrillin leads to connective tissue laxity. Therefore, patients typically present with **joint hypermobility** (hyperextensibility), not reduced mobility. Reduced joint mobility and contractures are more characteristic of **Congenital Contractural Arachnodactyly (Beals Syndrome)**, which involves the FBN2 gene. **Analysis of incorrect options:** * **Arachnodactyly:** This refers to abnormally long, slender fingers ("spider-like"). It is a classic skeletal feature of Marfan’s, often assessed via the Walker-Murdoch (wrist) and Steinberg (thumb) signs. * **Dislocation of the lens (Ectopia lentis):** This occurs in ~60% of patients. Characteristically, the dislocation is **upward and outward (superior-temporal)** due to weakness in the ciliary zonules. * **Mitral regurgitation:** Cardiovascular complications are the leading cause of mortality. Mitral valve prolapse (MVP) leading to mitral regurgitation is common [1], alongside the more life-threatening **cystic medial necrosis** of the aorta, which leads to aortic root dilation and dissection. **High-Yield Clinical Pearls for NEET-PG:** * **Ghent Criteria:** Used for diagnosis (focuses on FBN1 mutation, Ectopia lentis, and Aortic root aneurysm). * **Arm span to Height ratio:** Typically >1.05 in Marfan’s. * **Homocystinuria vs. Marfan’s:** Both present with tall stature and ectopia lentis. However, Homocystinuria features **downward** lens dislocation, intellectual disability, and a prothrombotic state. * **Management:** Beta-blockers or ARBs (Losartan) are used to slow the rate of aortic root dilation.

Question 22: Which of the following diseases is X-linked?

A. Thalassemia
B. Colour blindness (Correct Answer)
C. Sickle cell anemia
D. Galactosemia

Explanation: The correct answer is **Colour blindness**. This condition is inherited in an **X-linked recessive** pattern. The genes responsible for the red and green photopigments are located on the X chromosome. Because males have only one X chromosome (XY), a single mutated copy of the gene causes the disease. Females (XX) are typically asymptomatic carriers unless they inherit two mutated copies. **Analysis of Incorrect Options:** * **Thalassemia (A):** This is an **Autosomal Recessive** disorder. It involves mutations in the globin gene clusters located on Chromosome 16 (Alpha-thalassemia) and Chromosome 11 (Beta-thalassemia). * **Sickle cell anemia (C):** This is an **Autosomal Recessive** disorder caused by a point mutation in the $\beta$-globin gene on Chromosome 11, leading to the substitution of Valine for Glutamic acid at the 6th position. * **Galactosemia (D):** This is an **Autosomal Recessive** metabolic disorder, most commonly caused by a deficiency of the enzyme Galactose-1-phosphate uridyltransferase (GALT). **High-Yield Clinical Pearls for NEET-PG:** * **Common X-linked Recessive Disorders:** Remember the mnemonic **"G-CHESS"**: **G**6PD deficiency, **C**olour blindness/Chronic Granulomatous Disease, **H**emophilia A & B, **E**mer-Dreifuss muscular dystrophy, **S**teinert’s (Myotonic) dystrophy (some forms), and **S**pinal Muscular Atrophy. Also include **Duchenne Muscular Dystrophy [1]** and **Lesch-Nyhan Syndrome**. * **Rule of Thumb:** Most enzyme deficiencies are Autosomal Recessive, while structural protein defects are often Autosomal Dominant. * **X-linked Dominant:** Examples include Alport Syndrome and Vitamin D-resistant rickets (Hypophosphatemic rickets).

Question 23: Which of the following is NOT an X-linked dominant condition?

A. Familial hypophosphatemic rickets
B. Rett syndrome
C. Fragile X syndrome
D. Duchenne's muscular dystrophy (Correct Answer)

Explanation: **Explanation:** The correct answer is **D. Duchenne’s muscular dystrophy (DMD)**. **1. Why D is correct:** Duchenne’s muscular dystrophy is an **X-linked recessive (XLR)** disorder caused by a mutation in the *DMD* gene, which encodes the protein dystrophin [1]. In XLR conditions, males are primarily affected because they have only one X chromosome (hemizygous). Females are typically asymptomatic carriers unless they have Turner syndrome or skewed X-inactivation. **2. Why the other options are incorrect:** * **A. Familial hypophosphatemic rickets:** This is the classic prototype of **X-linked dominant (XLD)** inheritance. It involves a mutation in the *PHEX* gene, leading to phosphate wasting in the kidneys. * **B. Rett syndrome:** This is an **XLD** neurodevelopmental disorder (mutation in *MECP2*). It is almost exclusively seen in females because it is usually lethal in hemizygous males in utero. * **C. Fragile X syndrome:** This is inherited as an **XLD** condition with variable expressivity and incomplete penetrance. It is caused by a CGG trinucleotide repeat expansion in the *FMR1* gene. **3. NEET-PG High-Yield Clinical Pearls:** * **X-Linked Dominant Rule:** An affected father will pass the trait to **all** of his daughters but **none** of his sons. * **DMD vs. Becker’s:** Both are XLR. DMD is a "frameshift" mutation (complete absence of dystrophin), while Becker’s is an "in-frame" mutation (truncated/functional dystrophin), leading to a milder phenotype. * **Gower’s Sign:** Classically seen in DMD due to proximal muscle weakness. * **Other XLD conditions to remember:** Alport syndrome (some forms), Incontinentia Pigmenti, and Focal Dermal Hypoplasia (Goltz syndrome).

Question 24: Which of the following conditions is not primarily caused by a genetic mutation?

A. Diabetes mellitus type II (Correct Answer)
B. Cystic fibrosis
C. Hemophilia
D. Alpha 1 antitrypsin deficiency

Explanation: The core concept tested here is the distinction between **monogenic (Mendelian) disorders** and **multifactorial (polygenic) diseases**. [1] **Why Diabetes Mellitus Type II (DM-II) is the correct answer:** DM-II is a **multifactorial disease**. While it has a strong genetic predisposition (often stronger than Type I), it is not caused by a single primary mutation. Instead, it results from a complex interplay between **polygenic susceptibility** (multiple gene variants) and **environmental triggers** such as obesity, sedentary lifestyle, and aging. [1] It does not follow a classic Mendelian inheritance pattern. **Why the other options are incorrect:** * **Cystic Fibrosis:** A classic **Autosomal Recessive** disorder caused by mutations in the *CFTR* gene on chromosome 7. [2] * **Hemophilia:** An **X-linked Recessive** bleeding disorder caused by mutations in genes encoding Factor VIII (Hemophilia A) or Factor IX (Hemophilia B). * **Alpha-1 Antitrypsin Deficiency:** An **Autosomal Codominant** disorder caused by mutations in the *SERPINA1* gene, leading to emphysema and liver cirrhosis. **NEET-PG High-Yield Pearls:** * **Strongest Genetic Link:** Between DM-I and DM-II, **DM-II** has a higher concordance rate in monozygotic twins (up to 90%). * **MODY (Maturity Onset Diabetes of the Young):** Unlike DM-II, MODY is **monogenic** (Autosomal Dominant). The most common type is **MODY 3** (*HNF1-alpha* mutation). * **Polygenic vs. Monogenic:** Most common chronic diseases (HTN, DM-II, CAD) are polygenic, whereas rare "textbook" diseases are usually monogenic. [1]

Question 25: Dissecting haematoma is a clinical complication occurring in which of the following conditions?

A. Turner's syndrome
B. Klinefelter's syndrome
C. Down's syndrome
D. Marfan syndrome (Correct Answer)

Explanation: Explanation: Marfan Syndrome (Correct Answer): Marfan syndrome is an autosomal dominant connective tissue disorder caused by a mutation in the FBN1 gene on chromosome 15, which encodes Fibrillin-1 [1]. Fibrillin-1 is essential for the structural integrity of elastic fibers. A deficiency leads to cystic medial necrosis (degeneration of the aortic media). This structural weakness makes the aorta highly susceptible to a dissecting haematoma (Aortic Dissection), where blood enters the media through an intimal tear [2]. This is the most common cause of mortality in these patients [1, 2]. Why other options are incorrect: * Turner’s Syndrome (45, XO): While Turner’s syndrome is associated with cardiovascular issues like Coarctation of the Aorta and bicuspid aortic valve (which can predispose to dissection), it is not the primary "textbook" association for dissecting haematoma compared to the systemic elastic fiber defect in Marfan syndrome [2]. * Klinefelter’s Syndrome (47, XXY): This condition is characterized by hypogonadism and infertility. Cardiovascular complications are rare, though there is a slightly increased risk of mitral valve prolapse and venous thromboembolism. * Down’s Syndrome (Trisomy 21): The most common cardiac associations are Endocardial Cushion Defects (ASD/VSD). It does not involve the cystic medial necrosis required for a dissecting haematoma. High-Yield Clinical Pearls for NEET-PG: * Aortic Dissection: The most common site is the ascending aorta (Stanford Type A). * Marfanoid Habitus: Seen in Marfan syndrome, Homocystinuria, and MEN 2B. * Ocular Finding: Marfan syndrome typically presents with ectopia lentis (upward dislocation), whereas Homocystinuria presents with downward dislocation. * Diagnostic Criteria: The Ghent Nosology is used for diagnosing Marfan syndrome.

Question 26: Cystic fibrosis affects all systems EXCEPT:

A. Respiratory
B. Endocrine (Correct Answer)
C. Hepatobiliary
D. Genitourinary

Explanation: **Explanation:** Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the **CFTR gene**, which encodes a chloride channel [1]. This defect leads to the production of thick, viscid secretions in **exocrine glands**. **Why "Endocrine" is the correct answer:** The primary pathology of CF involves **exocrine dysfunction**. While CF frequently leads to "Cystic Fibrosis-Related Diabetes" (CFRD), this occurs because the thick secretions obstruct the pancreatic ducts, leading to secondary scarring and destruction of the islet cells (an **exocrine-driven** destruction of endocrine tissue). The endocrine system as a whole (pituitary, thyroid, adrenal) is not primarily affected by CFTR mutations. **Analysis of Incorrect Options:** * **Respiratory:** This is the most common cause of morbidity [2]. Thick mucus leads to bronchiectasis, recurrent infections (notably *Pseudomonas*), and nasal polyps [1]. * **Hepatobiliary:** Obstruction of bile ductules leads to focal biliary cirrhosis, neonatal cholestasis, and gallstones. * **Genitourinary:** Over 95% of males are infertile due to **Congenital Bilateral Absence of the Vas Deferens (CBAVD)** [1]. In females, thick cervical mucus can reduce fertility. **High-Yield Clinical Pearls for NEET-PG:** * **Gold Standard Diagnosis:** Sweat Chloride Test (>60 mEq/L). * **Most Common Mutation:** ΔF508 (Class II mutation - protein misfolding). * **Pancreatic Status:** 85-90% of patients have pancreatic exocrine insufficiency (malabsorption/steat同年rhea). * **GI Complication:** Meconium ileus is a classic presenting sign in neonates. * **Microbiology:** *Staphylococcus aureus* is common in early childhood; *Pseudomonas aeruginosa* is the dominant pathogen in adults.

Question 27: A patient presents with multiple odontogenic cysts, excessive length of bones, and hyperexcitability of joints. What is the most likely diagnosis?

A. Ehlers-Danlos syndrome
B. Marfan syndrome (Correct Answer)
C. Down syndrome
D. Reiter's syndrome

Explanation: ### Explanation **Correct Answer: B. Marfan syndrome** **Why it is correct:** Marfan syndrome is an autosomal dominant connective tissue disorder caused by a mutation in the **FBN1 gene** on chromosome 15, which encodes **Fibrillin-1**. This leads to a defect in the extracellular matrix and TGF-̢ signaling. * **Skeletal Features:** The "excessive length of bones" refers to **dolichostenomelia** (long, thin limbs) and arachnodactyly. * **Joints:** Defective fibrillin leads to ligamentous laxity, manifesting as **hyperexcitability (hypermobility) of joints**. * **Oral/Dental:** While less common than cardiovascular issues, Marfan syndrome is associated with high-arched palates, dental crowding, and **odontogenic cysts** (specifically keratocystic odontogenic tumors). **Why the other options are incorrect:** * **A. Ehlers-Danlos syndrome:** While it features joint hypermobility and skin hyperextensibility, it does not typically present with the "excessive length of bones" (marfanoid habitus) or specific odontogenic cysts. * **C. Down syndrome:** Characterized by Trisomy 21, presenting with intellectual disability, flat facial profile, and hypotonia, but not the tall stature or long bone overgrowth seen here. * **D. Reiter’s syndrome (Reactive Arthritis):** A triad of urethritis, conjunctivitis, and arthritis following an infection. It does not involve genetic bone overgrowth or odontogenic cysts. **High-Yield Clinical Pearls for NEET-PG:** * **Cardiovascular:** The most common cause of death is **Aortic Root Dilatation** leading to dissection or Mitral Valve Prolapse (MVP). * **Ocular:** **Ectopia Lentis** (dislocation of the lens) is classic; specifically **upward and outward (superotemporal)** displacement. (Contrast with Homocystinuria: Downward and inward). * **Steinberg Sign:** Thumb projects beyond the ulnar border of the clenched fist. * **Walker-Murdoch Sign:** Thumb and fifth finger overlap when encircling the opposite wrist.

Question 28: Which of the following conditions is associated with Turner syndrome?

A. Coarctation of the aorta (Correct Answer)
B. Aortic dissection
C. Aortic regurgitation
D. Pulmonic stenosis

Explanation: **Explanation:** **Turner Syndrome (45, XO)** is a common chromosomal abnormality in females characterized by short stature, streak ovaries, and specific congenital cardiovascular malformations [1]. **1. Why Coarctation of the Aorta is Correct:** Approximately 30% of patients with Turner syndrome have congenital heart defects. The most classic and high-yield association is **Coarctation of the Aorta** (pre-ductal type), occurring in about 10–15% of cases. The underlying mechanism is related to lymphatic obstruction during fetal development, which alters hemodynamics in the developing aorta. In coarctation of the aorta, radiofemoral delay may be noted and some female patients have the features of Turner's syndrome [3]. Additionally, **Bicuspid Aortic Valve (BAV)** is the most common overall cardiac anomaly (up to 30%). **2. Analysis of Incorrect Options:** * **B. Aortic Dissection:** While patients with Turner syndrome are at a significantly increased risk for aortic dissection (due to BAV or hypertension), it is a *complication* or an acquired event rather than a primary congenital condition associated with the syndrome's diagnosis. * **C. Aortic Regurgitation:** This may occur secondary to a bicuspid aortic valve or aortic root dilation, but it is not the primary diagnostic association tested in the context of congenital defects. * **D. Pulmonic Stenosis:** This is the classic cardiac association for **Noonan Syndrome** (often called "Pseudo-Turner syndrome" because of similar physical features like webbed neck, but occurring in both males and females with a 46, XX/XY karyotype) [2]. **NEET-PG High-Yield Pearls:** * **Most common cardiac anomaly:** Bicuspid Aortic Valve. * **Most characteristic vascular anomaly:** Coarctation of the Aorta. * **Karyotype:** 45, XO (Monosomy X) is most common [1]; Mosaicism (45,X/46,XX) carries a lower risk of anomalies. * **Renal association:** Horseshoe kidney. * **Dermatoglyphics:** Increased total ridge count on fingertips. * **Gold Standard Diagnosis:** Chromosomal Karyotyping.

Question 29: Thalassemia shows which kind of inheritance?

A. Autosomal recessive (Correct Answer)
B. Autosomal dominant
C. X-linked recessive
D. X-linked dominant

Explanation: **Explanation:** **1. Why Autosomal Recessive is Correct:** Thalassemia is a quantitative hemoglobinopathy characterized by the reduced synthesis of alpha or beta-globin chains [1]. It follows an **autosomal recessive** pattern of inheritance. This means a child must inherit one mutated gene from each parent (two copies total) to manifest the clinical disease (Thalassemia Major). If an individual inherits only one mutated gene, they become a carrier (Thalassemia Trait/Minor), who is usually asymptomatic but can pass the gene to offspring. **2. Why Other Options are Incorrect:** * **Autosomal Dominant:** In these disorders, a single copy of the mutant gene is sufficient to cause the disease (e.g., Marfan Syndrome, Achondroplasia). Thalassemia carriers do not manifest the full disease phenotype. * **X-linked Recessive:** These involve mutations on the X chromosome and primarily affect males (e.g., Hemophilia A/B, G6PD deficiency). Thalassemia affects males and females with equal frequency and severity. * **X-linked Dominant:** These are rare conditions where a single mutation on the X chromosome causes disease in both sexes (e.g., Alport Syndrome, Vitamin D resistant rickets). **3. High-Yield Clinical Pearls for NEET-PG:** * **Beta-Thalassemia:** Caused by mutations in the HBB gene on **Chromosome 11** [2]. * **Alpha-Thalassemia:** Caused by deletions in the HBA1/HBA2 genes on **Chromosome 16**. * **Microcytic Hypochromic Anemia:** Thalassemia is a classic differential; it is distinguished from Iron Deficiency Anemia by a **Mentzer Index < 13** (MCV/RBC count). * **Target Cells:** A characteristic finding on the peripheral blood smear. * **Hb Electrophoresis:** The gold standard for diagnosis (shows increased HbA2 and HbF in Beta-Thalassemia) [1].

Question 30: Which of the following statements about congenital adrenal hyperplasia is not true?

A. 21-alpha hydroxylase deficiency is the most common cause.
B. Males present with precocious puberty.
C. Females present with ambiguous genitalia.
D. Hypokalemic alkalosis is seen. (Correct Answer)

Explanation: **Explanation:** Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders characterized by a deficiency in enzymes required for cortisol synthesis [1]. **Why Option D is the correct answer (Not True):** In the most common form of CAH (21-hydroxylase deficiency), there is a lack of mineralocorticoids (aldosterone). This leads to "salt-wasting," characterized by **hyponatremia, hyperkalemia, and metabolic acidosis**. Therefore, the statement that "hypokalemic alkalosis is seen" is false. Hypokalemic alkalosis is instead characteristic of conditions with mineralocorticoid excess, such as Conn’s syndrome or 11-beta hydroxylase deficiency (where 11-deoxycorticosterone builds up). **Analysis of Incorrect Options:** * **Option A:** Correct. **21-alpha hydroxylase deficiency** accounts for >90% of CAH cases. * **Option B:** Correct. Excess androgens lead to **isosexual precocious puberty** in males (early development of secondary sexual characteristics but small testes). * **Option C:** Correct. In females, high levels of adrenal androgens in utero cause virilization, leading to **ambiguous genitalia** (clitoromegaly, labial fusion) at birth. **High-Yield Clinical Pearls for NEET-PG:** 1. **21-Hydroxylase Deficiency:** Most common; presents with salt-wasting, hypotension, and high **17-hydroxyprogesterone** levels [1]. 2. **11-Beta Hydroxylase Deficiency:** Second most common; presents with **hypertension** and hypokalemia due to the buildup of 11-deoxycorticosterone (DOC). 3. **17-Alpha Hydroxylase Deficiency:** Presents with hypertension but **delayed puberty/primary amenorrhea** (decreased sex hormones). 4. **Mnemonic:** If the enzyme starts with **1** (11, 17), it causes **HTN** (Hypertension). If the enzyme ends with **1** (11, 21), it causes **Virilization**.

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