Genetics and Disease — MCQs

Genetics and Disease Indian Medical PG Practice Questions and MCQs

Question 271: Which one of the following is an autosomal recessive disorder?

A. Cystic fibrosis (Correct Answer)
B. Huntington's disease
C. Marfan syndrome
D. Neurofibromatosis type 1

Explanation: ***Cystic fibrosis*** - **Cystic fibrosis** is caused by mutations in the **CFTR gene**, leading to defective **chloride channel** function. - It is an **autosomal recessive disorder**, meaning an individual must inherit two copies of the mutated gene (one from each parent) to be affected. *Huntington's disease* - **Huntington's disease** is an **autosomal dominant disorder** caused by a mutation in the HTT gene. - Only one copy of the mutated gene is sufficient to cause the disease, resulting in progressive neurodegeneration. *Marfan syndrome* - **Marfan syndrome** is an **autosomal dominant disorder** affecting connective tissue, caused by mutations in the FBN1 gene. - It results in skeletal, ocular, and cardiovascular abnormalities due to defective **fibrillin-1**. *Neurofibromatosis type 1* - **Neurofibromatosis type 1** is an **autosomal dominant disorder** caused by mutations in the NF1 gene. - It is characterized by multiple neurofibromas, café-au-lait macules, and Lisch nodules.

Question 272: What is the mode of inheritance for the most common form of hypophosphatemic rickets?

A. Autosomal Recessive (AR)
B. Autosomal Dominant (AD)
C. X-Linked Recessive (XR)
D. X-Linked Dominant (XD) (Correct Answer)

Explanation: ***X-Linked Dominant (XD)*** - The most common form of hypophosphatemic rickets is **X-linked hypophosphatemic rickets (XLH)**, which is inherited in an X-linked dominant pattern. - This condition is caused by mutations in the **PHEX gene** on the X chromosome, leading to impaired phosphate reabsorption in the kidneys. *Autosomal Recessive (AR)* - While some rare forms of hypophosphatemic rickets exist with **autosomal recessive** inheritance, they are not the most common. - These forms typically involve mutations in genes affecting phosphate transport or vitamin D metabolism, distinct from the primary defect in XLH. *Autosomal Dominant (AD)* - There are also rare **autosomal dominant** forms of hypophosphatemic rickets, such as hereditary hypophosphatemic rickets with hypercalciuria (HHRH) or autosomal dominant hypophosphatemic rickets (ADHR). - However, these are less common than the X-linked dominant form (XLH). *X-Linked Recessive (XR)* - **X-linked recessive** inheritance typically affects males more severely and exclusively, with carrier females usually unaffected or mildly affected. - In X-linked dominant conditions like XLH, both males and females are affected, though females may exhibit variable expressivity.

Question 273: Which of the following statements is NOT true about Alport's syndrome?

A. It is inherited in an X-linked pattern.
B. It causes nerve deafness.
C. It leads to glomerulonephritis.
D. It is caused by mutations in type I collagen. (Correct Answer)

Explanation: ***It is caused by mutations in type I collagen.*** - Alport's syndrome is primarily caused by mutations in genes encoding **type IV collagen**, not type I collagen [1]. - These mutations lead to defects in the **glomerular basement membrane**, inner ear, and eye [1]. *It is inherited in an X-linked pattern.* - The most common form of Alport's syndrome (around 85%) is inherited in an **X-linked recessive pattern**, due to mutations in the *COL4A5* gene. - This means males are typically more severely affected than females. *It causes nerve deafness.* - Individuals with Alport's syndrome often develop **sensorineural hearing loss**, which is a form of nerve deafness. - This symptom usually progresses from high-frequency hearing loss to profound deafness. *It leads to glomerulonephritis.* - The characteristic renal feature of Alport's syndrome is a progressive **glomerulonephritis**, eventually leading to **end-stage renal disease (ESRD)**. - This is due to the structural defects in the **glomerular basement membrane**, causing hematuria and proteinuria [1].

Question 274: Which of the following conditions is associated with ectopia lentis?

A. Homocystinuria (Correct Answer)
B. Alport syndrome
C. Lowe syndrome
D. Sulphite oxidase deficiency

Explanation: ***Homocystinuria*** - **Ectopia lentis** (lens dislocation) is a common and characteristic ocular manifestation of homocystinuria. - The lens typically dislocates **downward and inward**, differentiating it from Marfan syndrome. *Alport syndrome* - Characterized by **glomerulonephritis**, **sensorineural hearing loss**, and ocular abnormalities. - Ocular manifestations include **anterior lenticonus** (which can be mistaken for ectopia lentis in some descriptions), posterior polymorphous corneal dystrophy, and retinal flecks, but not classic ectopia lentis. *Lowe syndrome* - Also known as oculocerebrorenal syndrome of Lowe, it primarily affects the **eyes, brain, and kidneys**. - Ocular features include **congenital cataracts** and glaucoma, but not ectopia lentis. *Sulphite oxidase deficiency* - This is a rare metabolic disorder affecting the metabolism of sulfur-containing amino acids, leading to severe neurological symptoms. - While it can manifest with **cataracts** and **lens subluxation** in some cases, ectopia lentis is more characteristically associated with homocystinuria, and the overall clinical picture of sulphite oxidase deficiency is dominated by severe neurological impairment.

Question 275: What is Reifenstein syndrome?

A. Partial androgen insensitivity syndrome due to receptor mutation. (Correct Answer)
B. Complete androgen insensitivity syndrome with female external genitalia
C. 5-alpha reductase deficiency causing ambiguous genitalia
D. Gonadal dysgenesis with streak gonads

Explanation: Partial androgen insensitivity syndrome due to receptor mutation. - **Reifenstein syndrome** is a form of **partial androgen insensitivity syndrome (PAIS)**, characterized by varying degrees of undervirilization in 46,XY individuals. [4] - It results from mutations in the **androgen receptor (AR) gene**, leading to impaired androgen signaling. [4] *Complete androgen insensitivity syndrome with female external genitalia* - This describes **complete androgen insensitivity syndrome (CAIS)**, where affected individuals are 46,XY with completely female external genitalia, normal breast development, but no uterus. [4] - Unlike Reifenstein syndrome, there are no signs of virilization. [4] *5-alpha reductase deficiency causing ambiguous genitalia* - **5-alpha reductase deficiency** impedes the conversion of testosterone to the more potent **dihydrotestosterone (DHT)**, which is crucial for external male genital development. - While it causes **ambiguous genitalia**, it's a defect in hormone metabolism, not the androgen receptor itself. *Gonadal dysgenesis with streak gonads* - **Gonadal dysgenesis** refers to conditions where the gonads (testes or ovaries) fail to develop or develop abnormally, often leading to **streak gonads**. [3] - This is a primary gonadal developmental defect, distinct from disorders of androgen action or synthesis. [1], [2]

Question 276: What is the complete classic triad of findings that defines Young's syndrome?

A. Azoospermia, bronchiectasis, and chronic sinusitis (Correct Answer)
B. Oligospermia, bronchiectasis, and chronic sinusitis
C. Azoospermia, asthma, and chronic rhinitis
D. Azoospermia, chronic bronchitis, and nasal polyps

Explanation: ***Azoospermia, bronchiectasis, and chronic sinusitis*** - Young's syndrome is characterized by the triad of **azoospermia** (due to obstructive epididymal dysfunction), **bronchiectasis**, and **chronic sinusitis** [1]. - This syndrome primarily affects **middle-aged men** and is often mistaken for cystic fibrosis due to similar respiratory symptoms. *Azoospermia, asthma, and chronic rhinitis* - This option incorrectly lists **asthma** and **chronic rhinitis** instead of bronchiectasis and chronic sinusitis. - While respiratory symptoms are part of Young's syndrome, specifically **bronchiectasis** and **sinusitis** are key [1]. *Oligospermia, bronchiectasis, and chronic sinusitis* - This option is incorrect because Young's syndrome is defined by **azoospermia** (complete absence of sperm), not just **oligospermia** (low sperm count). - The obstructive nature of the epididymal dysfunction in Young's syndrome leads to a complete lack of sperm. *Azoospermia, chronic bronchitis, and nasal polyps* - This option incorrectly identifies **chronic bronchitis** and **nasal polyps** as part of the classic triad. - The correct respiratory components are **bronchiectasis** and **chronic sinusitis**, which signify persistent inflammation and structural lung changes rather than simply bronchitis.

Question 277: Which condition is associated with calcification of the intervertebral disc?

A. Gout
B. Rheumatoid
C. Alkaptonuria (Correct Answer)
D. Psoriasis

Explanation: ***Alkaptonuria*** - **Alkaptonuria** is a rare autosomal recessive disorder characterized by a deficiency of the enzyme **homogentisate 1,2-dioxygenase**, leading to the accumulation of **homogentisic acid**. - This accumulation results in the deposition of a **dark pigment (ochre pigment)** in connective tissues, including the intervertebral discs, causing **calcification (ochronosis)** and early degenerative arthritis. *Gout* - **Gout** is caused by the deposition of **monosodium urate crystals** in joints and soft tissues, leading to inflammation and pain [1]. - While it can affect various joints, it does not typically cause **calcification of intervertebral discs**; rather, it can form tophi in periarticular soft tissues [1]. *Rheumatoid* - **Rheumatoid arthritis** is a chronic autoimmune inflammatory disease primarily affecting the **synovial lining of joints**, leading to joint destruction and deformity. - It does not involve the **calcification of intervertebral discs**; spinal involvement is usually restricted to the cervical spine, particularly the atlantoaxial joint. *Psoriasis* - **Psoriasis** is a chronic inflammatory skin condition, which in some cases can be associated with **psoriatic arthritis**, an inflammatory arthritis. - Psoriatic arthritis primarily affects peripheral joints, the sacroiliac joints, and the spine, but it does not cause **calcification of the intervertebral discs** as seen in alkaptonuria.

Question 278: Which syndrome is characterized by oro-cutaneous hamartomatous tumors, gastrointestinal polyps, and abnormalities of the breast, thyroid gland, and genitourinary system?

A. Juvenile polyposis - involves juvenile polyps in the gastrointestinal tract, without systemic hamartomas.
B. Cowden's syndrome - a genetic disorder involving multiple hamartomas and systemic abnormalities, including breast, thyroid, and genitourinary systems. (Correct Answer)
C. Peutz-Jeghers syndrome - features pigmented lesions and gastrointestinal hamartomas, without systemic involvement.
D. Familial adenomatous polyposis (FAP) - involves multiple adenomatous polyps and a high risk of colorectal cancer.

Explanation: **Cowden's syndrome** - It is an **autosomal dominant** disorder caused by a germline mutation in the **PTEN tumor suppressor gene**. - Characterized by **multiple hamartomas** in various tissues, including distinctive mucocutaneous lesions (e.g., facial trichilemmomas, oral papillomas), gastrointestinal polyps, and an increased risk of specific cancers, such as those of the **breast**, **thyroid**, and **genitourinary system**. *Juvenile polyposis* - This syndrome is characterized by the presence of **juvenile polyps** predominantly in the colon and rectum, with a potential for malignant transformation [1]. - It is generally not associated with the wide array of oro-cutaneous hamartomas or systemic abnormalities seen in Cowden's Syndrome. *Peutz-Jeghers syndrome* - Characterized by **melanin spots** on the buccal mucosa, lips, and digits, along with characteristic **hamartomatous polyps** mainly in the small intestine [1]. - While it involves gastrointestinal polyps, it typically does not present with the extensive oro-cutaneous hamartomas or the specific systemic abnormalities of the breast, thyroid, and genitourinary system that define Cowden's syndrome. *Familial adenomatous polyposis (FAP)* - Defined by the development of **hundreds to thousands of adenomatous polyps** in the colon and rectum, driven by a mutation in the **APC gene** [2]. - While it involves numerous gastrointestinal polyps and a high risk of colorectal cancer, it does not typically feature the oro-cutaneous hamartomas or the distinct systemic abnormalities (breast, thyroid, genitourinary) characteristic of Cowden's syndrome [2].

Question 279: A 43-year-old man who had a subarachnoid hemorrhage from an intracranial aneurysm 8 years ago and has also experienced progressive renal impairment associated with hematuria is most likely to have which diagnosis?

A. A genetic condition causing hypertension due to sodium retention
B. A genetic disorder causing renal cysts and associated with intracranial aneurysms (Correct Answer)
C. A condition characterized by cystic dilation of renal pyramids
D. An autoimmune condition causing glomerulonephritis and pulmonary hemorrhage

Explanation: **A genetic disorder causing renal cysts and associated with intracranial aneurysms** - The combination of **intracranial aneurysm** causing subarachnoid hemorrhage and **progressive renal impairment with hematuria** strongly points to an underlying genetic disorder like **Autosomal Dominant Polycystic Kidney Disease (ADPKD)** [1]. - ADPKD is characterized by the development of numerous **renal cysts**, leading to renal dysfunction, and is associated with extrarenal manifestations, including a significantly increased risk of developing **intracranial aneurysms**. *A condition characterized by cystic dilation of renal pyramids* - This description refers to **medullary sponge kidney**, a condition involving cystic dilation of the collecting ducts in the renal pyramids. - While it can cause hematuria and kidney stones, it is **not typically associated with intracranial aneurysms or progressive renal failure of the severity described**. *A genetic condition causing hypertension due to sodium retention* - Conditions like **Liddle's syndrome** or **Gordon's syndrome (pseudohypoaldosteronism type II)** cause hypertension due to dysregulation of sodium handling in the kidneys. - However, these conditions do **not typically lead to progressive renal impairment with hematuria** or have an association with **intracranial aneurysms**. *An autoimmune condition causing glomerulonephritis and pulmonary hemorrhage* - This describes **Goodpasture's syndrome (anti-GBM disease)**, an autoimmune condition characterized by a rapidly progressive glomerulonephritis and often pulmonary hemorrhage. - While it causes renal impairment and hematuria, it is **not associated with intracranial aneurysms**, and the presentation is usually more acute and severe.

Question 280: Which one of the following diseases is classified as an autosomal dominant disorder?

A. Hemochromatosis
B. Phenylketonuria
C. Maturity onset diabetes of the young (Correct Answer)
D. Glucose-6 phosphate dehydrogenase deficiency

Explanation: ***Maturity onset diabetes of the young*** - **Maturity onset diabetes of the young (MODY)** is a genetically heterogeneous group of single-gene disorders characterized by beta-cell dysfunction and impaired insulin secretion, typically inherited in an **autosomal dominant pattern** [1]. - A single copy of the mutated gene is sufficient to cause the condition, leading to diabetes usually before the age of 25, often without obesity or autoantibodies [1]. *Hemochromatosis* - **Hemochromatosis** is typically inherited in an **autosomal recessive pattern**, meaning two copies of the mutated gene (e.g., *HFE* gene) are required for the disease to manifest. - It leads to excessive iron absorption and tissue iron overload. *Phenylketonuria* - **Phenylketonuria (PKU)** is an **autosomal recessive disorder** caused by a deficiency in the enzyme **phenylalanine hydroxylase**, necessitating two mutated gene copies for the disease to occur. - This leads to the accumulation of phenylalanine, causing neurological damage if untreated. *Glucose-6 phosphate dehydrogenase deficiency* - **Glucose-6 phosphate dehydrogenase (G6PD) deficiency** is an **X-linked recessive disorder**, meaning the gene is located on the X chromosome and typically affects males more severely. - Females can be carriers, and hemizygous males (having only one X chromosome) will express the disorder if they inherit the mutated gene.

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Principles of Medical Genetics

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Genetic Testing and Counseling

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Single Gene Disorders

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Chromosomal Disorders

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Mitochondrial Diseases

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Pharmacogenomics

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Cancer Genetics

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Genetics of Common Diseases

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Epigenetics and Disease

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Genetic Basis of Developmental Disorders

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Ethical Issues in Medical Genetics

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Gene Therapy and Precision Medicine

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