Molecular Pathology Practice Questions

Q: Which of the following is true in Klinefelter syndrome?

Subnormal intelligence. **Explanation:** **Klinefelter Syndrome (47, XXY)** is the most common sex chromosome aneuploidy in males, occurring due to meiotic nondisjunction. **Why Option C is Correct:** While many individuals with Klinefelter syndrome have normal intelligence, there is a statistically significant shift in the IQ distribution. On average, the IQ is 10–15 points lower than siblings [1]. Most patients exhibit **subnormal intelligence** or specific cognitive deficits, particularly in verbal skills, reading, and executive function. The severity of intellectual impairment often correlates with the number of extra X chromosomes (e.g., 48, XXXY is more severe than 47, XXY). **Analysis of Incorrect Options:** * **A. Short stature:** Incorrect. Patients typically have **tall stature** [1] with disproportionately long legs (eunuchoid habitus) due to the extra copy of the *SHOX* gene located on the X chromosome. [1] * **B. Pituitary adenoma:** Incorrect. There is no established association between Klinefelter syndrome and pituitary adenomas. The hormonal profile shows primary testicular failure (hypergonadotropic hypogonadism) [2] with high FSH/LH and low testosterone. [1] * **C. Breast adenoma:** Incorrect. While **gynecomastia** (present in ~50% of cases) is a hallmark, it is a proliferation of glandular tissue, not an adenoma. Notably, these patients have a **20–50 times higher risk of male breast cancer** (carcinoma) compared to the general male population. [2] **High-Yield Clinical Pearls for NEET-PG:** * **Karyotype:** Most common is 47, XXY. * **Testicular Findings:** Small, firm testes (atrophy) with hyalinization and fibrosis of seminiferous tubules. [1] * **Hormonal Profile:** ↓ Testosterone, ↑ LH, ↑ FSH, ↑ Estradiol. [1] * **Associated Risks:** Increased risk of Germ Cell Tumors (specifically mediastinal extragonadal GCTs), Systemic Lupus Erythematosus (SLE), and Osteoporosis. [2]

Q: Comment on the diagnosis.

Turner syndrome. ***Turner syndrome*** - The **45,X monosomy** karyotype is pathognomonic for Turner syndrome, representing complete absence of one sex chromosome. - Clinical features include **short stature**, **webbed neck**, **shield chest**, and **primary amenorrhea** due to ovarian dysgenesis. *Klinefelter syndrome* - Characterized by **47,XXY karyotype** with an extra X chromosome, not the 45,X monosomy shown. - Presents with **tall stature**, **gynecomastia**, **small testes**, and **infertility** in males. *Down syndrome* - Results from **trisomy 21 (47,XX/XY,+21)** karyotype, not a sex chromosome abnormality. - Features include **intellectual disability**, **characteristic facial features**, and **congenital heart defects**. *Cri-du-chat syndrome* - Caused by **deletion of chromosome 5p (46,XX/XY,del(5p))**, not sex chromosome monosomy. - Characterized by **cat-like cry**, **microcephaly**, **intellectual disability**, and **growth retardation**.

Q: Down's syndrome is most commonly caused by?

Maternal nondisjunction. **Explanation:** Down’s syndrome (Trisomy 21) is the most common chromosomal aberration in humans. The correct answer is **Maternal nondisjunction** because approximately **95%** of cases are caused by a numerical error where chromosomes fail to separate during meiosis. 1. **Why Maternal Nondisjunction is Correct:** In about 90–95% of trisomy 21 cases, the extra chromosome is of maternal origin. This occurs due to failure of separation of homologous chromosomes during **Meiosis I** (most common) or sister chromatids during Meiosis II. The risk increases significantly with advanced maternal age (especially >35 years) due to the prolonged "dictyotene" stage of oocytes. 2. **Why other options are incorrect:** * **Paternal nondisjunction:** While it can occur, it accounts for only about 3–5% of cases. * **Translocation:** Seen in ~3–4% of cases. It usually involves a Robertsonian translocation between chromosomes 14 and 21. Unlike nondisjunction, this type can be inherited from a carrier parent and is independent of maternal age. * **Mosaicism:** Seen in ~1–2% of cases. It occurs due to mitotic nondisjunction *after* fertilization, resulting in two different cell lines (some with 46 and some with 47 chromosomes). These patients often have milder clinical features. **High-Yield Clinical Pearls for NEET-PG:** * **Most common cause:** Maternal nondisjunction (95%). * **Most common mechanism:** Meiosis I error. * **Recurrence risk:** ~1% for nondisjunction; up to 10–15% if the mother is a 14;21 translocation carrier. * **Screening:** Low AFP, Low Estriol, High hCG, and High Inhibin-A (Quadruple test) are characteristic markers.

Q: A normal couple has one daughter affected with Cystic fibrosis. They are now planning to have another child. What is the chance of siblings being affected by the disease?

25%. **Explanation:** **1. Understanding the Correct Answer (C):** Cystic Fibrosis (CF) is an **Autosomal Recessive (AR)** disorder. For a "normal" couple to have an affected child, both parents must be asymptomatic **obligate carriers** (genotype: **Aa**). According to Mendelian inheritance, when two carriers (Aa x Aa) conceive [1]: * 25% chance of an affected child (**aa**) * 50% chance of a carrier child (**Aa**) * 25% chance of a genetically normal child (**AA**) Therefore, for every subsequent pregnancy, there is a **25% (1 in 4)** risk of the sibling being affected. **2. Why Other Options are Incorrect:** * **A (0%):** This would only occur if at least one parent was homozygous dominant (AA) and not a carrier. * **B (50%):** This risk is associated with **Autosomal Dominant** conditions (if one parent is affected) or the risk of being a **carrier** in an AR condition. * **D (75%):** This represents the probability of a child being **unaffected** (Normal + Carrier) in an AR cross. **3. Clinical Pearls for NEET-PG:** * **Most common mutation:** ΔF508 on Chromosome 7 (CFTR gene) [2]. * **Diagnosis:** Sweat Chloride test (>60 mEq/L) is the gold standard [1]. * **Key Associations:** Meconium ileus (newborns), Bilateral Absence of Vas Deferens (infertility in males), and recurrent *Pseudomonas* infections [2]. * **Rule of Thumb:** In AR pedigrees, if the parents are normal but a child is affected, always assume both parents are carriers (25% recurrence risk) [1]. If an unaffected sibling of an affected child asks about their carrier status, the probability is **2/3** (since the 'aa' possibility is already ruled out) [1].

Question 1

Which of the following is true in Klinefelter syndrome?

Accepted Answer

Subnormal intelligence

Answer

Short stature

Answer

Pituitary adenoma

Answer

Breast adenoma

Question 2

Which one of the following is not a polygenic disorder?

Accepted Answer

Down's syndrome

Answer

Diabetes mellitus

Answer

Coronary heart disease

Answer

Congenital heart disease

Question 3

Comment on the diagnosis.

Accepted Answer

Turner syndrome

Answer

Klinefelter syndrome

Answer

Down syndrome

Answer

Cri-du-chat syndrome

Question 4

Down's syndrome is most commonly caused by?

Accepted Answer

Maternal nondisjunction

Answer

Paternal nondisjunction

Answer

Translocation

Answer

Mosaicism

Question 5

What is the most common microdeletion syndrome?

Accepted Answer

Velocardiofacial (VCF) syndrome

Answer

WAGR syndrome

Answer

Prader-Willi syndrome

Answer

Angelman syndrome

Question 6

A normal couple has one daughter affected with Cystic fibrosis. They are now planning to have another child. What is the chance of siblings being affected by the disease?

Accepted Answer

25%

Answer

0%

Answer

50%

Answer

75%

Question 7

What is the typical number of chromosomes in an individual with Klinefelter syndrome?

Accepted Answer

47

Answer

46

Answer

45

Answer

44

Question 8

Which of the following is false regarding cystic fibrosis?

Accepted Answer

Associated with chromosome 7p

Answer

Associated with the CFTR gene

Answer

Autosomal recessive inheritance

Answer

Recurrent respiratory tract infection

Question 9

Edward syndrome is characterized by which of the following chromosomal abnormalities?

Accepted Answer

Trisomy 18

Answer

Trisomy 13

Answer

Trisomy 21

Answer

Trisomy 20

Question 10

All are present in Fragile X syndrome, except:

Accepted Answer

Mental retardation and macroorchidism

Answer

Mental retardation and microorchidism

Answer

Mental retardation and microorchidism

Answer

Microorchidism and large facies

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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