Molecular Pathology Practice Questions

Q: Which of the following conditions is not associated with an increased risk of malignancy?

Turner syndrome. **Explanation:** The question evaluates the association between chromosomal aneuploidies and the risk of malignancy. While many genetic syndromes predispose individuals to cancer due to genomic instability or hormonal imbalances, **Turner Syndrome (45, XO)** is generally **not** associated with an overall increased risk of malignancy compared to the general population. In fact, the risk of breast cancer is significantly lower in Turner patients due to ovarian dysgenesis and low estrogen levels. The only specific risk is a **gonadoblastoma**, which occurs only if there is cryptic Y-chromosome mosaicism (45,X/46,XY). **Analysis of Options:** * **Down’s Syndrome (Trisomy 21):** Strongly associated with a 10–20 fold increased risk of **Acute Leukemia** (AMKL/M7 in children <3 years and ALL in older children). * **Noonan Syndrome:** Often called "Pseudo-Turner," this autosomal dominant condition is associated with an increased risk of **Juvenile Myelomonocytic Leukemia (JMML)** and certain solid tumors like neuroblastoma. * **Klinefelter Syndrome (47, XXY):** These patients have a significantly higher risk of **Breast Cancer** (20–50 times higher than normal males) and **Extragonadal Germ Cell Tumors** (specifically mediastinal teratomas). **NEET-PG High-Yield Pearls:** 1. **Turner Syndrome:** Most common cause of primary amenorrhea; characterized by "streak ovaries," webbed neck, and coarctation of the aorta. 2. **Klinefelter Syndrome:** Most common cause of male hypogonadism and infertility; associated with taurodontism. 3. **Cancer Association:** Always remember the "Down-Leukemia" and "Klinefelter-Breast Cancer" links, as these are frequent examiners' favorites.

Q: Which of the following conditions is NOT inherited in an autosomal recessive pattern?

Marfan's syndrome. **Explanation:** The correct answer is **Marfan’s syndrome** because it follows an **Autosomal Dominant (AD)** inheritance pattern. It is caused by a mutation in the **FBN1 gene** on chromosome 15, which encodes **Fibrillin-1**, a critical glycoprotein for the structural integrity of the extracellular matrix. Since it is dominant, a single mutated allele from one parent is sufficient to cause the disease. **Analysis of Options:** * **Sickle cell anemia (A):** This is a classic **Autosomal Recessive (AR)** disorder caused by a point mutation in the HBB gene (Glu6Val). Clinical manifestation occurs only in the homozygous state (HbSS). * **Phenylketonuria (B):** An **AR** metabolic disorder involving a deficiency of the enzyme phenylalanine hydroxylase. It requires two defective alleles for the phenotype to appear. * **Wilson’s disease (D):** An **AR** disorder of copper metabolism caused by mutations in the **ATP7B gene** on chromosome 13. **NEET-PG High-Yield Pearls:** 1. **Marfan’s Syndrome:** Look for "Tall stature, Ectopia lentis (upward dislocation), and Aortic root dilatation." It exhibits **pleiotropy** (one gene affecting multiple systems). 2. **Mnemonic for AR diseases:** "Many Metabolic" diseases are AR (e.g., Glycogen storage diseases, Galactosemia, Cystic Fibrosis, and most enzyme deficiencies). 3. **Mnemonic for AD diseases:** "Structural" proteins are often AD (e.g., Marfan’s, Achondroplasia, Hereditary Spherocytosis, Osteogenesis Imperfecta) [1]. 4. **Exceptions:** Most enzyme deficiencies are AR, but **Hunter Syndrome** and **G6PD deficiency** are X-linked Recessive.

Q: Which of the following is true for Klinefelter's syndrome?

Tall stature. **Explanation:** **Klinefelter Syndrome (47, XXY)** is the most common cause of male hypogonadism and occurs due to meiotic non-disjunction of sex chromosomes. 1. **Why "Tall Stature" is correct:** Patients with Klinefelter syndrome possess an extra X chromosome. The **SHOX gene** (Short Stature Homeobox gene), located on the distal short arms of the X and Y chromosomes, remains active. An extra copy of the SHOX gene leads to increased skeletal growth, resulting in **tall stature** and elongated lower limbs (eunuchoid body habitus) [1]. 2. **Why the other options are incorrect:** * **Option A (45, XO):** This is the karyotype for **Turner Syndrome**, which presents in females with short stature and streak ovaries [1]. * **Option C (Normal IQ):** While many patients have near-normal intelligence, there is a statistically significant association with **mild intellectual disability** or learning disabilities (specifically verbal lag). The degree of impairment often increases with the number of extra X chromosomes (e.g., 48, XXXY). * **Option D (Normal testes):** This is incorrect. The hallmark of Klinefelter is **testicular dysgenesis**. Patients present with small, firm testes, hyalinization of seminiferous tubules, and Leydig cell hyperplasia. **High-Yield Clinical Pearls for NEET-PG:** * **Karyotype:** Most commonly 47, XXY. * **Hormonal Profile:** Low Testosterone, **High FSH and LH** (Hypergonadotropic hypogonadism), and increased Estradiol. * **Clinical Features:** Gynecomastia (increased risk of male breast cancer), infertility (azoospermia), and reduced secondary male sexual characteristics. * **Barr Body:** Positive (due to the extra X chromosome). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 173-174.

Question 1

Which of the following conditions is not associated with an increased risk of malignancy?

Accepted Answer

Turner syndrome

Answer

Down's syndrome

Answer

Noonan syndrome

Answer

Klinefelter syndrome

Question 2

Which of the following is an autosomal dominant metabolic disorder?

Accepted Answer

Familial hypercholesterolemia

Answer

Cystic fibrosis

Answer

Phenylketonuria

Answer

Alpha-1 anti-trypsin deficiency

Question 3

A female patient presents with a 2 x 2 cm firm mass in the upper outer quadrant of the breast. She has a family history of ovarian carcinoma. Which investigation needs to be done to assess for a specific gene mutation?

Accepted Answer

BRCA-2

Answer

p53

Answer

Her 2/Neu gene

Answer

C-myc gene

Question 4

Which of the following conditions is NOT inherited in an autosomal recessive pattern?

Accepted Answer

Marfan's syndrome

Answer

Sickle cell anemia

Answer

Phenylketonuria

Answer

Wilson's disease

Question 5

Which of the following is true for Klinefelter's syndrome?

Accepted Answer

Tall stature

Answer

45, XO

Answer

Normal Intelligence Quotient

Answer

Normal testes and genitalia

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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