Genetics and Disease Practice Questions

Q: A middle-aged man notices that he can no longer fit in his shoes and observes enlargement of his jaw and phalanges. Which hormone mediates these effects?

Somatomedin. ### Explanation The clinical presentation of increasing shoe size, jaw enlargement (prognathism), and phalangeal thickening in an adult is classic for **Acromegaly**, which results from the hypersecretion of Growth Hormone (GH) after epiphyseal closure [2]. **Why Somatomedin is Correct:** While GH is the primary hormone secreted by the pituitary adenoma, its peripheral effects—especially linear and bony growth—are mediated by **Somatomedin C**, also known as **Insulin-like Growth Factor 1 (IGF-1)** [1]. GH stimulates the liver to produce IGF-1, which then acts on tissues to promote protein synthesis and skeletal growth [1]. In clinical practice, measuring serum IGF-1 is the most reliable screening test for Acromegaly because it has a longer half-life and lacks the pulsatile secretion pattern of GH [3]. **Why the Other Options are Incorrect:** * **ACTH (A):** Stimulates the adrenal cortex to produce cortisol. Excess leads to Cushing’s syndrome (moon face, buffalo hump), not bony enlargement. * **TRH (B):** A hypothalamic hormone that stimulates the release of TSH and Prolactin. It does not mediate bone or soft tissue growth. * **TGF-beta (D):** A cytokine involved in cell growth, differentiation, and development, but it is not the mediator of GH-induced systemic growth in Acromegaly. **High-Yield Clinical Pearls for NEET-PG:** * **Screening Test:** Serum IGF-1 levels (Somatomedin C). * **Confirmatory Test:** Oral Glucose Tolerance Test (OGTT) with GH measurement [3]. Failure to suppress GH <1 ng/mL after 75g glucose is diagnostic. * **Most Common Cause:** Somatotroph adenoma of the anterior pituitary. * **Radiology:** Look for "spade-like" phalanges on X-ray and enlargement of the sella turcica on MRI. * **Treatment of Choice:** Transsphenoidal surgery [3]. Medical management includes Somatostatin analogues (Octreotide).

Q: If both parents are carriers for an autosomal recessive disorder, what are the chances of their offspring being affected?

1 in 1. **Explanation** In autosomal recessive (AR) inheritance, a disease manifests only when an individual inherits two copies of the mutated gene (homozygous state). When both parents are **carriers** (heterozygous, Aa), the probability of inheritance for each pregnancy is determined by the Punnett square: * **AA (25%):** Unaffected, non-carrier. * **Aa (50%):** Unaffected, carrier. * **aa (25%):** **Affected.** Therefore, the chance of an offspring being affected is **1 in 4 (25%)**. **Note on the provided answer key:** In standard genetics, the correct answer is **A (1 in 4)**. If the provided key marks **D (1 in 1)** as correct, it is likely a typographical error in the source material or refers to a specific scenario where both parents are *affected* (aa x aa), not carriers. For NEET-PG, always follow the 1:2:1 genotypic ratio for carrier parents. **Analysis of Options:** * **A (1 in 4):** Correct. Represents the 25% probability of inheriting two recessive alleles (aa). * **B (1 in 2):** Incorrect. This represents the probability of an offspring being a **carrier** (50%). * **C (1 in 3):** Incorrect. This is the probability of an **unaffected** child being a carrier (conditional probability). * **D (1 in 1):** Incorrect for carriers. This only occurs if both parents are homozygous affected (aa x aa). **Clinical Pearls for NEET-PG:** 1. **Consanguinity:** Increases the risk of AR disorders by increasing the likelihood that both parents carry the same rare mutation. 2. **Horizontal Transmission:** AR disorders typically appear in a single generation (siblings) rather than every generation. 3. **Common Examples:** Cystic Fibrosis, Sickle Cell Anemia, Thalassemia, and most Inborn Errors of Metabolism (except Hunter Syndrome and Fabry disease, which are X-linked).

Q: Which of the following is not an autosomal dominant disorder?

Alkaptonuria. The correct answer is **Alkaptonuria** because it is an **Autosomal Recessive (AR)** disorder, whereas the other options are primarily inherited in an Autosomal Dominant (AD) pattern. **1. Why Alkaptonuria is the correct answer:** Alkaptonuria is a rare metabolic disorder caused by a deficiency of the enzyme **homogentisate 1,2-dioxygenase**. This leads to the accumulation of homogentisic acid. It follows an autosomal recessive inheritance pattern. Clinically, it is characterized by the "classic triad": dark urine (on standing), ochronosis (bluish-black pigmentation of connective tissues), and ochronotic arthritis. **2. Why the other options are incorrect:** * **Polycystic Kidney Disease (PKD):** While there is an AR form (ARPKD), the most common form (90% of cases) is **Autosomal Dominant (ADPKD)**, caused by mutations in *PKD1* or *PKD2* genes. In medical exams, "PKD" without qualification usually refers to the AD form. * **Ehlers-Danlos Syndrome (EDS):** Most common subtypes (like Hypermobile and Classical) follow an **Autosomal Dominant** inheritance, though rare variants can be recessive. * **Osteogenesis Imperfecta (OI):** The majority of cases (Type I-IV), involving mutations in *COL1A1* or *COL1A2*, are inherited as **Autosomal Dominant** traits. **NEET-PG High-Yield Pearls:** * **Mnemonic for AD disorders:** "Very Powerful DOMINANT" (Von Willebrand, Polycystic kidney, Dystrophia myotonica, Osteogenesis imperfecta, Marfan, Intermittent porphyria, Noonan, Achondroplasia, Neurofibromatosis, Tuberous sclerosis). * **Alkaptonuria Diagnosis:** Ferric chloride test (turns urine persistent black) and Benedict’s test (positive for reducing sugars). * **Treatment:** Nitisinone is used to reduce the production of homogentisic acid.

Q: Which of the following diseases is NOT caused by a point mutation?

Hereditary sensory and motor neuropathy type 1. ### Explanation The correct answer is **Hereditary Sensory and Motor Neuropathy Type 1 (HSMN-1)**, also known as **Charcot-Marie-Tooth disease type 1A (CMT1A)**. **1. Why HSMN-1 is the correct answer:** Unlike the other options, CMT1A is typically caused by a **large-scale DNA duplication**, not a point mutation. Specifically, it involves a **1.5 Mb duplication** of the **PMP22 gene** on chromosome 17. This leads to an overexpression of the peripheral myelin protein 22, resulting in abnormal myelin structure and function. **2. Why the other options are incorrect:** * **Hemochromatosis:** Most commonly caused by a point mutation in the **HFE gene** (C282Y or H63D), where a single nucleotide change leads to an amino acid substitution [1]. * **Achondroplasia:** This is the most common cause of dwarfism and is caused by a specific point mutation in the **FGFR3 gene** (G380R), leading to a gain-of-function [2]. * **Alpha-1 Antitrypsin Deficiency:** The most severe form (PiZZ) is caused by a single point mutation (Glu342Lys) in the **SERPINA1 gene**, causing protein misfolding and accumulation in the liver [1]. ### NEET-PG Clinical Pearls * **CMT1A (HSMN-1):** Look for "stork leg" or "inverted champagne bottle" appearance of legs, pes cavus, and "onion bulb" formation on nerve biopsy due to repeated demyelination and remyelination. * **Achondroplasia:** 80% of cases are due to *de novo* mutations, often associated with advanced paternal age [2]. * **Point Mutations vs. Repeat Expansions:** Remember that Huntington’s and Fragile X are caused by **trinucleotide repeat expansions**, while CMT1A is a **duplication**. These are high-yield distinctions for "not a point mutation" questions [3].

Q: A 22-year-old man presents with arm span greater than height, subluxed lenses, and dilation of the aorta. What is the most likely diagnosis?

Marfan syndrome. **Explanation:** The clinical triad of **skeletal abnormalities** (arm span > height), **ectopia lentis** (subluxed lenses), and **aortic root dilation** is the classic presentation of **Marfan Syndrome** [1]. **1. Why Marfan Syndrome 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** [1]. Fibrillin-1 is essential for the structural integrity of the extracellular matrix and the regulation of TGF-β. * **Skeletal:** Patients exhibit a "marfanoid habitus" (tall stature, arachnodactyly, and an increased arm span-to-height ratio). * **Ocular:** Upward and outward (superotemporal) subluxation of the lens is a hallmark. * **Cardiovascular:** Cystic medial necrosis leads to aortic root dilation, which can progress to aortic dissection—the most common cause of mortality [1]. **2. Why Other Options are Incorrect:** * **Ehlers-Danlos Syndrome:** Characterized by skin hyperextensibility and joint hypermobility. While it involves vascular issues, it typically lacks the tall stature and specific lens subluxation seen here. * **Werner Syndrome:** A rare progeroid (premature aging) syndrome characterized by short stature, cataracts, and skin changes, not marfanoid features. * **Laurence-Moon-Biedl Syndrome:** A ciliopathy presenting with obesity, retinitis pigmentosa, polydactyly, and hypogonadism. **NEET-PG High-Yield Pearls:** * **Lens Subluxation:** Marfan = **Upward** (Superior); Homocystinuria = **Downward** (Interior). * **Diagnosis:** Based on the **Ghent Criteria**. * **Management:** Beta-blockers or ARBs (Losartan) are used to slow the rate of aortic dilation. * **Most common cause of death:** Aortic dissection/rupture [1].

Q: Which one of the following conditions is inherited in an autosomal recessive pattern?

Homocystinuria. **Explanation:** **Homocystinuria (Option A)** is the correct answer. It is an **autosomal recessive (AR)** metabolic disorder, most commonly caused by a deficiency of the enzyme **cystathionine beta-synthase (CBS)**. In NEET-PG, a high-yield rule of thumb is that almost all **inborn errors of metabolism** (enzyme deficiencies) follow an autosomal recessive inheritance pattern [1] (exceptions include Hunter syndrome and Fabry disease). **Analysis of Incorrect Options:** * **G6PD Deficiency (Option B):** This is an **X-linked recessive** condition. It is the most common red cell enzyme deficiency worldwide, leading to episodic hemolysis under oxidative stress. * **Myotonic Dystrophy (Option C):** This follows an **autosomal dominant** pattern. It is characterized by "anticipation" due to CTG trinucleotide repeat expansions on chromosome 19. * **Otospongiosis/Otosclerosis (Option D):** This is typically inherited in an **autosomal dominant** pattern with variable penetrance. It is a common cause of progressive conductive hearing loss in young adults. **Clinical Pearls for NEET-PG:** * **Homocystinuria vs. Marfan Syndrome:** Both present with tall stature and arachnodactyly. However, Homocystinuria features **downward (inferomedial)** lens subluxation, intellectual disability, and a high risk of **thromboembolism**. Marfan syndrome features upward (superotemporal) ectopia lentis and normal intelligence. * **Diagnosis:** Screened via the **Cyanide-nitroprusside test** (positive urine test). * **Treatment:** A subset of patients responds to high doses of **Vitamin B6 (Pyridoxine)**, which acts as a cofactor for the CBS enzyme [2].

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]

Question 1

A middle-aged man notices that he can no longer fit in his shoes and observes enlargement of his jaw and phalanges. Which hormone mediates these effects?

Accepted Answer

Somatomedin

Answer

Adrenocorticotropic hormone (ACTH)

Answer

Thyrotropin-releasing hormone (TRH)

Answer

Transforming growth factor beta (TGF-beta)

Question 2

Which disease is caused by the over-expression of a trinucleotide repeat?

Accepted Answer

Huntington's disease

Answer

Parkinson's disease

Answer

Caisson's disease

Answer

Addison's disease

Question 3

If both parents are carriers for an autosomal recessive disorder, what are the chances of their offspring being affected?

Accepted Answer

1 in 1

Answer

1 in 4

Answer

1 in 2

Answer

1 in 3

Question 4

Which of the following is not an autosomal dominant disorder?

Accepted Answer

Alkaptonuria

Answer

Polycystic kidney disease

Answer

Ehlers-Danlos syndrome

Answer

Osteogenesis imperfecta

Question 5

Which of the following diseases is NOT caused by a point mutation?

Accepted Answer

Hereditary sensory and motor neuropathy type 1

Answer

Hemochromatosis

Answer

Achondroplasia

Answer

Alpha 1 antitrypsin deficiency

Question 6

A 22-year-old man presents with arm span greater than height, subluxed lenses, and dilation of the aorta. What is the most likely diagnosis?

Accepted Answer

Marfan syndrome

Answer

Ehlers-Danlos syndrome

Answer

Werner syndrome

Answer

Laurence-Moon-Biedl syndrome

Question 7

Which one of the following conditions is inherited in an autosomal recessive pattern?

Accepted Answer

Homocystinuria

Answer

G6PD deficiency

Answer

Myotonic dystrophy

Answer

Otospongiosis

Question 8

Which of the following is true in Klinefelter syndrome?

Accepted Answer

Subnormal intelligence

Answer

Short stature

Answer

Pituitary adenoma

Answer

Breast adenoma

Question 9

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 10

If a parent is heterozygous and the other parent is homozygous for an autosomal-recessive gene, what will be the genetic outcome for their children?

Accepted Answer

50% of children will be affected, and the rest will be carriers.

Answer

75% of children will be affected.

Answer

No child will be affected, but all will be carriers.

Answer

25% of children will be affected, and the rest will be carriers.

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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