Genetics and Disease Practice Questions

Q: Males who are sexually underdeveloped with rudimentary testes and prostate glands, sparse pubic and facial hair, long arms and legs and large hands and feet are likely to have which chromosome complement?

47, XXY. The clinical presentation described—hypogonadism (rudimentary testes/prostate), lack of secondary sexual characteristics (sparse hair), and **eunuchoid body habitus** (long extremities)—is the classic triad of **Klinefelter Syndrome** [1]. **1. Why 47, XXY is correct:** Klinefelter Syndrome is the most common cause of congenital hypogonadism in males [2]. The presence of an extra X chromosome leads to testicular dysgenesis [2]. Specifically, the destruction of seminiferous tubules results in low testosterone and elevated gonadotropins (Hypergonadotropic Hypogonadism) [1]. The increased height and long limbs are attributed to the overexpression of the **SHOX gene** (located on the X chromosome), which remains active and delays epiphyseal closure. **2. Analysis of Incorrect Options:** * **45, XYY (Jacob’s Syndrome):** These individuals are usually phenotypically normal, very tall, and may have cystic acne or behavioral issues, but they do not have underdeveloped genitalia or sparse hair. * **46, XY:** This is the normal male karyotype. * **45, X0 (Turner Syndrome):** This presents in females with short stature, webbed neck, and streak ovaries [3]. It is the polar opposite of the tall, male phenotype described. **3. High-Yield Clinical Pearls for NEET-PG:** * **Lab Findings:** ↓ Testosterone, ↑ LH, ↑ FSH, and ↑ Estradiol (leading to **Gynecomastia**) [1]. * **Histology:** Fibrosis and hyalinization of seminiferous tubules with **Leydig cell hyperplasia** [1]. * **Key Risk:** These patients have a significantly higher risk of **Breast Cancer** (20x) and **Extragonadal Germ Cell Tumors** [4]. * **Mental Health:** Often associated with mild intellectual disability or executive dysfunction [1].

Q: Turner's syndrome is characterized by which of the following findings, except?

Tall stature. **Explanation:** Turner’s syndrome (45,XO) is the most common sex chromosome abnormality in females [1], [5]. The hallmark of this condition is **short stature**, not tall stature [1]. This is primarily due to the haploinsufficiency of the **SHOX gene** (Short Stature Homeobox gene) located on the distal part of the X chromosome. **Why "Tall Stature" is the correct answer (the exception):** Patients with Turner’s syndrome typically have a height below the 3rd percentile. Growth failure is often the most consistent clinical feature. In contrast, tall stature is associated with conditions like Marfan syndrome, Klinefelter syndrome (47,XXY), or XYY syndrome [2]. **Analysis of incorrect options:** * **Renal malformations:** Approximately 30-50% of patients have renal anomalies, the most classic being the **Horseshoe kidney**. Other findings include duplication of the collecting system. * **Primary amenorrhea:** This occurs due to **gonadal dysgenesis** (streak ovaries) [4]. The accelerated loss of oocytes leads to premature ovarian failure, resulting in hypergonadotropic hypogonadism [3]. * **Lymphedema:** Congenital lymphedema of the hands and feet is a common neonatal presentation [5]. It is caused by lymphatic hypoplasia and often results in a "webbed neck" (cystic hygroma) later in life. **High-Yield Clinical Pearls for NEET-PG:** * **Cardiac:** Bicuspid aortic valve (most common) and Coarctation of the aorta. * **Dermatological:** Multiple pigmented nevi and high-arched palate. * **Endocrine:** Increased risk of Hashimoto’s thyroiditis and Celiac disease. * **Karyotype:** 45,XO is the most common, but mosaicism (45,X/46,XX) can present with milder features and secondary amenorrhea [5].

Q: What is the cause of thick pancreatic secretions in cystic fibrosis?

Defect in chloride channel leading to water reabsorption. **Explanation:** The fundamental defect in Cystic Fibrosis (CF) is a mutation in the **CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene**, which encodes a cAMP-regulated chloride channel. **Why Option C is Correct:** In the pancreas and respiratory tract, the CFTR protein normally pumps chloride ions *out* of the epithelial cells into the lumen. This creates an osmotic gradient that draws water into the secretions, keeping them hydrated and fluid. In CF, the defective channel prevents chloride secretion. Consequently, there is a compensatory **increase in sodium and water reabsorption** from the lumen into the cells to maintain isotonicity. This dehydration of the luminal surface leads to the formation of viscid, inspissated (thick) secretions that obstruct pancreatic ducts, leading to exocrine insufficiency and fibrosis. **Why Other Options are Incorrect:** * **Option A & B:** While mucin clearance is impaired, the primary pathology is not an overproduction of mucin or a simple mechanical failure of the epithelium; it is the secondary result of the underlying electrolyte and water imbalance. * **Option D:** The primary defect is in the **chloride channel**, not the sodium channel (ENaC). While sodium reabsorption is increased, it is a secondary physiological response to the chloride transport failure. **High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** Most common mutation is **ΔF508** (Class II defect: protein misfolding and trafficking failure). * **Sweat Gland Paradox:** Unlike the pancreas, in sweat glands, CFTR normally *reabsorbs* chloride. Therefore, CF patients have **high sweat chloride** (>60 mEq/L), which is the gold standard for diagnosis. * **Meconium Ileus:** The earliest clinical manifestation of CF in neonates. * **Infertility:** 95% of males are infertile due to **Congenital Bilateral Absence of Vas Deferens (CBAVD)**.

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

Reduced joint mobility. 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.

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

Hypokalemic alkalosis is seen.. **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**.

Q: Which cardiac anomaly is commonly seen in Noonan's syndrome?

Pulmonary Stenosis. Explanation: Noonan’s syndrome is an autosomal dominant multisystem disorder, often referred to as the "Male Turner Syndrome" (though it affects both sexes). It is primarily caused by mutations in the **RAS-MAPK signaling pathway**, most commonly involving the **PTPN11 gene**. **Why Pulmonary Stenosis is Correct:** Congenital heart disease occurs in approximately 80% of patients with Noonan’s syndrome. The most characteristic lesion is **Valvular Pulmonary Stenosis (PS)**, often due to dysplastic pulmonary valves (seen in ~50% of cases). The second most common cardiac finding is **Hypertrophic Cardiomyopathy (HCM)**, specifically asymmetrical septal hypertrophy. **Analysis of Incorrect Options:** * **A. Ventricular Septal Defect (VSD):** While VSD can occur in many genetic syndromes (like Down syndrome), it is not the defining or most common lesion in Noonan’s. * **B. Atrial Septal Defect (ASD):** ASD (specifically Secundum type) is the second most common *structural* defect after PS in Noonan’s, but PS remains the classic "textbook" association for exams. * **D. Coarctation of the Aorta:** This is the classic cardiac association for **Turner Syndrome (45, XO)** [1]. Distinguishing Noonan’s (PS) from Turner’s (Coarctation/Bicuspid Aortic Valve) is a frequent high-yield NEET-PG pivot point. **High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** PTPN11 mutation (50% of cases). * **Phenotype:** Short stature, webbed neck, hypertelorism, and low-set ears (similar to Turner’s) [1]. * **Key Distinctions from Turner’s:** Noonan’s patients have **normal karyotypes**, can be male, and frequently present with **bleeding diathesis** (Factor XI deficiency) and **cryptorchidism**. * **Mnemonic:** **N**oonan = **N**orth (Pulmonary valve is "superior/north" to the Aortic valve).

Q: A 22-year-old patient presents with multiple neural tumors, pigmented iris hamartomas, and numerous tan macules on his skin. His father, paternal uncle, and paternal grandfather had a similar condition. What is the most likely diagnosis for this patient?

Neurofibromatosis type I. ### Explanation **Neurofibromatosis type I (NF1)**, also known as von Recklinghausen disease, is an **autosomal dominant** neurocutaneous syndrome caused by a mutation in the *NF1* gene on **chromosome 17**. The gene encodes **neurofibromin**, a tumor suppressor that negatively regulates the RAS pathway. The diagnosis is confirmed by the presence of classic clinical features described in the vignette: * **Tan macules:** These are **Café-au-lait spots** (usually ≥6 required for diagnosis). * **Pigmented iris hamartomas:** Known as **Lisch nodules**, which are pathognomonic for NF1. * **Multiple neural tumors:** These represent **neurofibromas** (cutaneous or plexiform). * **Family History:** The involvement of the father, uncle, and grandfather confirms an autosomal dominant inheritance pattern with high penetrance. **Analysis of Incorrect Options:** * **A. Ependymoma:** While associated with Neurofibromatosis type II (NF2), it is not a feature of NF1. NF2 is characterized by bilateral acoustic neuromas (schwannomas) and is linked to chromosome 22 [1]. * **B. Huntington disease:** An autosomal dominant neurodegenerative disorder characterized by chorea and dementia, caused by CAG triplet repeats on chromosome 4. It lacks cutaneous manifestations. * **C. Marfan syndrome:** A connective tissue disorder (FBN1 mutation) presenting with tall stature, ectopia lentis, and aortic root dilation, but not neural tumors or Lisch nodules. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for NF1:** "17 letters in von Recklinghausen" = **Chromosome 17**. * **Optic Glioma:** The most common CNS tumor associated with NF1. * **Skeletal Deformities:** Sphenoid wing dysplasia and pseudoarthrosis of the tibia are specific diagnostic criteria. * **Crowe Sign:** Axillary or inguinal freckling is a highly specific clinical sign for NF1.

Q: An 18-year-old patient presents with sebaceous cysts on the scalp and back of the neck, and an osteoma on the right mandible. Radiographs reveal multiple impacted supernumerary teeth in both jaws. These findings suggest which of the following conditions?

Gardner's syndrome. **Explanation** The clinical triad of **sebaceous (epidermoid) cysts**, **osteomas** (particularly of the mandible and skull), and **supernumerary teeth** is pathognomonic for **Gardner’s Syndrome**. **1. Why Gardner’s Syndrome is Correct:** Gardner’s syndrome is a clinical variant of **Familial Adenomatous Polyposis (FAP)**, caused by a mutation in the **APC gene** on chromosome 5q21. It is characterized by the systemic manifestation of: * **Colonic polyps:** 100% risk of progression to colorectal carcinoma if not treated. * **Extra-colonic bone findings:** Osteomas (most common in the mandible). * **Dental abnormalities:** Impacted supernumerary teeth, odontomas, and congenitally missing teeth. * **Soft tissue tumors:** Epidermoid cysts, fibromas, and desmoid tumors. **2. Why the Other Options are Incorrect:** * **Cleidocranial dysostosis:** While it features supernumerary teeth, it is characterized by clavicular hypoplasia (allowing shoulders to touch) and delayed closure of fontanelles, not osteomas or sebaceous cysts. * **Ectodermal dysplasia:** This typically presents with **hypodontia** (missing teeth) and conical-shaped teeth, along with sparse hair and anhidrosis, which contradicts the "supernumerary teeth" finding. * **Osteogenesis imperfecta:** Characterized by blue sclera, hearing loss, and multiple fractures due to Type I collagen defects. It does not present with osteomas or sebaceous cysts. **High-Yield Clinical Pearls for NEET-PG:** * **CHRPE:** Congenital Hypertrophy of Retinal Pigment Epithelium is often the earliest detectable sign of Gardner’s syndrome. * **Desmoid Tumors:** These are aggressive fibroblastic tumors that often occur post-surgery in Gardner’s patients. * **Screening:** Patients with these extra-intestinal markers must undergo immediate **colonoscopy**, as malignant transformation of polyps occurs by age 40.

Question 1

Males who are sexually underdeveloped with rudimentary testes and prostate glands, sparse pubic and facial hair, long arms and legs and large hands and feet are likely to have which chromosome complement?

Accepted Answer

47, XXY

Answer

45, XYY

Answer

46, XY

Answer

45, X0

Question 2

A family consists of a husband, wife, and children. The wife's father has Huntington's chorea. Which statement is true regarding this genetic condition?

Accepted Answer

If the wife does not develop the disease by age 50, her children will not be affected.

Answer

The chance of a child inheriting the disease is 1:4.

Answer

The disease can manifest up to the age of 50.

Answer

Huntington's chorea is caused by a point mutation in a gene.

Question 3

Turner's syndrome is characterized by which of the following findings, except?

Accepted Answer

Tall stature

Answer

Renal malformations

Answer

Primary amenorrhea

Answer

Lymphedema

Question 4

What is the cause of thick pancreatic secretions in cystic fibrosis?

Accepted Answer

Defect in chloride channel leading to water reabsorption

Answer

Overproduction of mucin

Answer

Failure to clear mucin due to epithelial dysfunction

Answer

Defect in sodium channel leading to water reabsorption

Question 5

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

Accepted Answer

Reduced joint mobility

Answer

Arachnodactyly

Answer

Dislocation of the lens

Answer

Mitral regurgitation

Question 6

Which of the following conditions is associated with Turner syndrome?

Accepted Answer

Coarctation of the aorta

Answer

Aortic dissection

Answer

Aortic regurgitation

Answer

Pulmonic stenosis

Question 7

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

Accepted Answer

Hypokalemic alkalosis is seen.

Answer

21-alpha hydroxylase deficiency is the most common cause.

Answer

Males present with precocious puberty.

Answer

Females present with ambiguous genitalia.

Question 8

Which cardiac anomaly is commonly seen in Noonan's syndrome?

Accepted Answer

Pulmonary Stenosis

Answer

Ventricular Septal Defect (VSD)

Answer

Atrial Septal Defect (ASD)

Answer

Coarctation of the Aorta

Question 9

A 22-year-old patient presents with multiple neural tumors, pigmented iris hamartomas, and numerous tan macules on his skin. His father, paternal uncle, and paternal grandfather had a similar condition. What is the most likely diagnosis for this patient?

Accepted Answer

Neurofibromatosis type I

Answer

Ependymoma

Answer

Huntington disease

Answer

Marfan syndrome

Question 10

An 18-year-old patient presents with sebaceous cysts on the scalp and back of the neck, and an osteoma on the right mandible. Radiographs reveal multiple impacted supernumerary teeth in both jaws. These findings suggest which of the following conditions?

Accepted Answer

Gardner's syndrome

Answer

Cleidocranial dysostosis

Answer

Ectodermal dysplasia

Answer

Osteogenesis imperfecta

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?