Genetics and Disease — MCQs

A 40-year-old male presented to the ER with generalized tonic-clonic seizure. This was his first episode and he gave a history of intermittent bloody stools for the past 5 months. Investigations included MRI scan of the head, CECT abdomen, and colonoscopy. What is the most common inheritance pattern of the condition suggested by this presentation?

Q156Medium

What is the most common cause of death in individuals with Klinefelter's syndrome?

Q157Easy

Hypokalemic periodic paralysis is inherited as an autosomal dominant disorder with incomplete penetrance. It is caused by a mutation in which of the following channels?

Q158Medium

Which of the following is NOT a mitochondrial disease?

Q159Easy

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

Q160Easy

What is the commonest mode of inheritance among diseases with Mendelian inheritance?

Genetics and Disease Indian Medical PG Practice Questions and MCQs

Question 151: Which one of the following is an autosomal dominant type of genetic disorder?

A. Color blindness
B. Hemophilia
C. Phenylketonuria
D. Tuberous sclerosis (Correct Answer)

Explanation: **Explanation:** **Tuberous Sclerosis (Option D)** is the correct answer. It is an **autosomal dominant (AD)** neurocutaneous syndrome caused by mutations in the *TSC1* (Hamartin) or *TSC2* (Tuberin) genes. In AD disorders, a single copy of the mutant gene is sufficient to cause the disease, typically manifesting in every generation. **Analysis of Incorrect Options:** * **Color Blindness (Option A) and Hemophilia (Option B):** These are classic examples of **X-linked recessive (XLR)** disorders. They primarily affect males, while females are typically asymptomatic carriers. * **Phenylketonuria (Option C):** This is an **autosomal recessive (AR)** metabolic disorder. It requires two copies of the defective gene (one from each parent) for the disease to manifest. Most enzyme deficiencies, like PKU, follow an AR inheritance pattern. **Clinical Pearls for NEET-PG:** * **Tuberous Sclerosis Triad (Vogt’s Triad):** Adenoma sebaceum (facial angiofibromas), seizures, and mental retardation (seen in only ~30% of cases). * **High-Yield Features:** Ash-leaf spots (hypopigmented macules - earliest sign), Shagreen patches, subependymal nodules (candle-guttering appearance), and Cardiac Rhabdomyomas. * **Mnemonic for AD Disorders:** "Very Powerful DOMINANT" – **V**on Willebrand/VHL, **P**olycystic Kidney (ADPKD), **D**ystrophia Myotonica, **O**steogenesis Imperfecta, **M**arfan, **I**ntermittent Porphyria, **N**eurofibromatosis, **A**chondroplasia, **N**oonan, **T**uberous Sclerosis.

Question 152: Which of the following is the primary cause of phenotypic heterogeneity?

A. Allele mutation (Correct Answer)
B. Variable penetrance
C. Allelic deletion
D. Variable expressivity

Explanation: **Explanation:** **Phenotypic heterogeneity** refers to the phenomenon where different mutations within the same gene (locus) result in different clinical presentations or distinct diseases [1]. **Why Allele Mutation is correct:** The primary driver of this heterogeneity is the specific nature of the **allele mutation**. Different types of mutations (e.g., missense vs. nonsense) or mutations at different positions within the same gene can lead to varying degrees of protein dysfunction [1]. For example, in *CFTR* gene mutations, some alleles cause classic Cystic Fibrosis with pancreatic insufficiency, while others result only in congenital bilateral absence of the vas deferens (CBAVD). Because the variation originates at the level of the specific allele, it is the fundamental cause of phenotypic diversity within a single genetic locus. **Analysis of Incorrect Options:** * **Variable Penetrance:** This refers to whether an individual with a specific genotype expresses the phenotype at all (an "all-or-none" phenomenon) [2]. It describes the proportion of individuals, not the variety of the disease manifestation itself. * **Allelic Deletion:** While a type of mutation, it is a specific structural change and not the broad mechanism defining phenotypic heterogeneity across different patients. * **Variable Expressivity:** This describes the *range* of signs and symptoms that occur in different people with the *same* genetic condition. While closely related, it is often influenced by modifier genes and environmental factors rather than being the primary cause of distinct clinical syndromes arising from the same locus [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Allelic Heterogeneity:** Different mutations at the same locus cause the same disease (e.g., over 1,000 different mutations in *CFTR* can cause Cystic Fibrosis). * **Locus Heterogeneity:** Mutations at different loci (different genes) cause the same disease (e.g., Osteogenesis Imperfecta can be caused by mutations in *COL1A1* or *COL1A2*). * **Pleiotropy:** A single gene mutation affecting multiple, seemingly unrelated organ systems (e.g., Marfan Syndrome).

Question 153: What is the genotype of a male with Down syndrome?

A. 46, XY
B. 47, XY (Correct Answer)
C. 45, XY
D. 47, XXY

Explanation: **Explanation:** **1. Correct Answer: B (47, XY)** Down syndrome is characterized by **Trisomy 21**, meaning there are three copies of chromosome 21 instead of the usual two. In a male, the normal chromosomal complement is 46, XY. The addition of one extra autosome (chromosome 21) brings the total count to **47**. Therefore, the genotype is written as **47, XY, +21** (often simplified to 47, XY in MCQ options). The most common cause (95% of cases) is meiotic non-disjunction, which is strongly associated with advanced maternal age. **2. Analysis of Incorrect Options:** * **A. 46, XY:** This represents a **genotypically normal male** [2]. While Down syndrome can rarely occur with 46 chromosomes due to Robertsonian Translocation, the phenotype still requires the genetic material of three chromosome 21s; however, 47, XY is the standard representation of the trisomic state. * **C. 45, XY:** This indicates **monosomy** (loss of a chromosome). Autosomal monosomies are generally incompatible with life [3]. * **D. 47, XXY:** This is the genotype for **Klinefelter Syndrome** [1]. While it also has 47 chromosomes, the extra chromosome is a sex chromosome (X), not an autosome. **3. NEET-PG High-Yield Pearls:** * **Most common cause:** Meiotic non-disjunction (95%). * **Translocation type:** Robertsonian translocation [t(14;21)] accounts for ~4% and is independent of maternal age. * **Screening:** First-trimester screening includes **increased Nuchal Translucency (NT)**, decreased PAPP-A, and increased β-hCG. * **Quadruple Test (2nd Trimester):** Low AFP, Low Estriol, High hCG, and **High Inhibin A** (Inhibin is the most sensitive marker here). * **Clinical Associations:** Endocardial cushion defects (ASD/VSD), early-onset Alzheimer’s, and increased risk of ALL (Acute Lymphoblastic Leukemia) and AML (specifically M7 subtype).

Question 154: A 36-year-old male patient with a family history of dementia is being considered for genetic testing. What type of genetic test is most appropriate in this scenario?

A. Genetic carrier test (Correct Answer)
B. Presymptomatic test
C. Post-symptomatic test
D. Genetic presymptomatic test

Explanation: **Explanation:** The correct answer is **Genetic carrier test**. In the context of a patient with a family history of a late-onset neurodegenerative disorder (like certain forms of dementia) who is currently asymptomatic, the goal is to identify if the individual carries a specific gene mutation that could be passed to offspring or manifest later in life [1]. 1. **Why Option A is correct:** A **Genetic Carrier Test** is used to identify individuals who carry one copy of a gene mutation that, when present in two copies (autosomal recessive) or located on the X chromosome, causes a genetic disorder [1]. In clinical genetics, this term is also broadly applied to screening individuals in families with known hereditary conditions to determine their risk status before symptoms appear. [1] 2. **Why other options are incorrect:** * **Presymptomatic test (B) & Genetic presymptomatic test (D):** While these terms are often used interchangeably in clinical practice, "Genetic carrier test" is the standardized terminology used in many medical examinations to describe the screening of an asymptomatic person with a positive family history. Furthermore, "Presymptomatic" specifically refers to conditions where the person *will* definitely develop the disease (e.g., Huntington’s), whereas carrier testing is broader. * **Post-symptomatic test (C):** This is a diagnostic test performed *after* a patient already shows clinical signs or symptoms of a disease to confirm a suspected genetic diagnosis. **Clinical Pearls for NEET-PG:** * **Huntington’s Disease:** The classic example of a condition requiring **presymptomatic testing** (Autosomal Dominant, CAG repeats). * **Carrier Screening:** Most commonly recommended for Autosomal Recessive conditions like Cystic Fibrosis, Thalassemia, and Spinal Muscular Atrophy. * **Ethical Note:** Genetic testing in asymptomatic individuals requires extensive pre-test and post-test counseling due to the psychological impact and implications for insurance/employment. [1]

Question 155: A 40-year-old male presented to the ER with generalized tonic-clonic seizure. This was his first episode and he gave a history of intermittent bloody stools for the past 5 months. Investigations included MRI scan of the head, CECT abdomen, and colonoscopy. What is the most common inheritance pattern of the condition suggested by this presentation?

A. Autosomal dominant (Correct Answer)
B. Autosomal recessive
C. X-linked recessive
D. X-linked dominant

Explanation: The clinical presentation of a middle-aged male with **generalized tonic-clonic seizures** (suggesting a brain tumor) and **intermittent bloody stools** (suggesting colonic polyposis) is classic for **Turcot Syndrome**. Turcot syndrome is a variant of hereditary polyposis syndromes characterized by the association of **familial adenomatous polyposis (FAP)** or Lynch syndrome with **Central Nervous System (CNS) tumors** (most commonly medulloblastoma or glioblastoma multiforme). 1. **Why Autosomal Dominant is correct:** The majority of hereditary polyposis syndromes, including **FAP (APC gene mutation)** and **Lynch Syndrome (Mismatch repair genes)**, follow an **Autosomal Dominant (AD)** inheritance pattern [1]. Since Turcot syndrome is a phenotypic variant of these conditions, it primarily follows the AD pattern. (Note: A rarer subtype associated with *MUTYH* mutations follows autosomal recessive inheritance [2], but AD remains the classic and most common pattern tested). 2. **Why other options are incorrect:** * **Autosomal Recessive:** While some rare polyposis conditions like MAP (MUTYH-associated polyposis) are recessive [2], they are not the "most common" pattern for the classic Turcot/FAP presentation. * **X-linked Patterns:** There are no major hereditary colorectal cancer syndromes that follow X-linked inheritance. ### Clinical Pearls for NEET-PG: * **Turcot Syndrome Type 1:** Associated with Lynch Syndrome (HNPCC); common CNS tumor is **Glioblastoma Multiforme**. * **Turcot Syndrome Type 2:** Associated with FAP; common CNS tumor is **Medulloblastoma**. * **Gardner Syndrome:** Another AD variant of FAP presenting with colonic polyps + Osteomas (mandible) + Soft tissue tumors (Desmoid tumors) + Sebaceous cysts [2]. * **Rule of Thumb:** Most "Cancer Predisposition Syndromes" involving tumor suppressor genes (APC, BRCA, RB, TP53) are inherited in an **Autosomal Dominant** fashion [1].

Question 156: What is the most common cause of death in individuals with Klinefelter's syndrome?

A. Infections (Correct Answer)
B. Cardiovascular disease
C. Respiratory disease
D. Suicide

Explanation: **Explanation:** **Klinefelter’s Syndrome (47, XXY)** is the most common sex chromosome aneuploidy in males. While these patients have a shortened life expectancy (by approximately 2–5 years), the leading cause of mortality is often misunderstood. 1. **Why Infections are the Correct Answer:** Large-scale epidemiological studies (such as those by Price et al. and Bojesen et al.) have consistently shown that **infectious diseases** (specifically pneumonia and sepsis) are the most common cause of death. The underlying mechanism is thought to be related to an altered immune response and hormonal imbalances (hypogonadism), which may predispose these individuals to severe infections. 2. **Analysis of Incorrect Options:** * **Cardiovascular Disease:** While there is an increased risk of venous thromboembolism (VTE), pulmonary embolism, and mitral valve prolapse, it ranks behind infections and respiratory causes in terms of total mortality. * **Respiratory Disease:** Chronic obstructive pulmonary disease (COPD) and pneumonia are significant contributors, but "Infections" is the broader, more specific primary category cited in mortality data. * **Suicide:** Although there is a higher prevalence of psychiatric comorbidities and learning disabilities, suicide is not the leading cause of death. **High-Yield Clinical Pearls for NEET-PG:** * **Karyotype:** 47, XXY (most common); presence of **Barr body** in a male [1]. * **Clinical Features:** Tall stature, gynecomastia, small firm testes (testicular dysgenesis), and female-pattern hair distribution [1]. * **Hormonal Profile:** **Hypergonadotropic Hypogonadism** (Low Testosterone, High LH, and High FSH) [1]. * **Malignancy Risk:** Significantly increased risk of **Male Breast Cancer** (20-50 times higher than normal males) and **Extragonadal Germ Cell Tumors** (specifically mediastinal teratomas) [1]. * **Metabolic:** Increased risk of Type 2 Diabetes and Metabolic Syndrome [1].

Question 157: Hypokalemic periodic paralysis is inherited as an autosomal dominant disorder with incomplete penetrance. It is caused by a mutation in which of the following channels?

A. Sodium channel
B. Potassium channel
C. Chloride channel
D. Calcium channel (Correct Answer)

Explanation: **Explanation:** **Hypokalemic Periodic Paralysis (HOKPP)** is the most common form of periodic paralysis [1]. It is characterized by episodic muscle weakness triggered by factors that lower serum potassium levels, such as high-carbohydrate meals or strenuous exercise [1]. **Why the Correct Answer is Right:** The primary defect in **Type 1 HOKPP** (accounting for ~70% of cases) is a mutation in the **CACNA1S gene**, which encodes the **α1-subunit of the L-type voltage-gated calcium channel** (Dihydropyridine receptor) in skeletal muscle. This mutation results in an aberrant "gating pore current" that leads to muscle membrane depolarization and inexcitability during periods of low extracellular potassium. **Analysis of Incorrect Options:** * **A. Sodium channel:** Mutations in the **SCN4A** gene (Sodium channel) cause **Hyperkalemic** Periodic Paralysis [1]. While a small subset of HOKPP (Type 2) is caused by sodium channel mutations, the classic and most frequent association taught for exams is the calcium channel. * **B. Potassium channel:** Mutations in potassium channels (e.g., KCNJ2) are associated with **Andersen-Tawil Syndrome**, which presents with periodic paralysis, cardiac arrhythmias (long QT), and skeletal abnormalities. * **C. Chloride channel:** Mutations in the **CLCN1** chloride channel cause **Myotonia Congenita** (Thomsen and Becker diseases), characterized by delayed muscle relaxation rather than episodic paralysis [1]. **Clinical Pearls for NEET-PG:** * **Triggers:** High carb intake (insulin shifts K+ intracellularly), rest after exercise, and stress [1]. * **Treatment:** Acute attacks are treated with oral/IV Potassium. Prophylaxis involves **Acetazolamide** (carbonic anhydrase inhibitor) or potassium-sparing diuretics. * **Thyrotoxic Periodic Paralysis:** A common differential in Asian males; it presents identically to HOKPP but is associated with hyperthyroidism.

Question 158: Which of the following is NOT a mitochondrial disease?

A. Leber's hereditary optic neuropathy
B. Kearns-Sayre syndrome
C. Progressive external ophthalmoplegia
D. Spino-cerebellar ataxia (Correct Answer)

Explanation: The correct answer is **D. Spino-cerebellar ataxia (SCA)**. **1. Why Spino-cerebellar ataxia is the correct answer:** Mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA) or nuclear DNA encoding mitochondrial proteins, typically following a **maternal inheritance** pattern [1]. **Spino-cerebellar ataxia (SCA)**, however, is a group of neurodegenerative disorders primarily caused by **autosomal dominant** mutations. Most common types (like SCA1, 2, 3, and 7) are characterized by **CAG trinucleotide repeat expansions** in nuclear DNA, not mitochondrial dysfunction. **2. Analysis of Incorrect Options:** * **A. Leber’s Hereditary Optic Neuropathy (LHON):** A classic mitochondrial disease characterized by painless, subacute bilateral vision loss [1]. It is caused by point mutations in mtDNA (e.g., G11778A). * **B. Kearns-Sayre Syndrome (KSS):** A mitochondrial DNA deletion syndrome characterized by the triad of onset before age 20, chronic progressive external ophthalmoplegia (CPEO), and pigmentary retinopathy [1]. * **C. Progressive External Ophthalmoplegia (PEO):** This involves weakness of the extraocular muscles. While it can be part of multisystem syndromes (like KSS), it is fundamentally a manifestation of mitochondrial myopathy [1]. **3. NEET-PG High-Yield Pearls:** * **Maternal Inheritance:** All children of an affected mother inherit the disease, but an affected father never passes it on [1]. * **Heteroplasmy:** The presence of a mixture of wild-type and mutant mtDNA; the "threshold effect" determines clinical severity. * **Ragged Red Fibers:** On Gomori trichrome stain, these are the hallmark of mitochondrial myopathies (accumulation of diseased mitochondria under the sarcolemma). * **Common Mnemonics:** Remember **MELAS** (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) and **MERRF** (Myoclonic Epilepsy with Ragged Red Fibers).

Question 159: Which of the following conditions is inherited in an autosomal dominant pattern?

A. Achondroplasia (Correct Answer)
B. Hemochromatosis
C. Wilson's disease
D. Cystic fibrosis

Explanation: **Explanation:** **Achondroplasia (Correct Answer):** Achondroplasia is the most common cause of short-limb dwarfism and is inherited in an **autosomal dominant (AD)** pattern [1]. It is caused by a gain-of-function mutation in the **FGFR3 gene** (Fibroblast Growth Factor Receptor 3) on chromosome 4p. While it is AD, approximately 80% of cases arise from *de novo* mutations, often associated with advanced paternal age. **Incorrect Options:** * **Hemochromatosis (B):** This is an **autosomal recessive (AR)** disorder, most commonly involving the HFE gene (C282Y mutation). It leads to excessive iron absorption and deposition in organs like the liver, heart, and pancreas. * **Wilson's Disease (C):** This is an **AR** disorder of copper metabolism caused by mutations in the ATP7B gene on chromosome 13, leading to copper accumulation in the liver and basal ganglia (Kayser-Fleischer rings). * **Cystic Fibrosis (D):** This is a classic **AR** disorder caused by mutations in the CFTR gene on chromosome 7, affecting chloride transport and leading to thick secretions in the lungs and pancreas. **High-Yield Clinical Pearls for NEET-PG:** * **Rule of Thumb:** Most structural protein defects (e.g., Achondroplasia, Marfan syndrome) are **Autosomal Dominant**, whereas most enzyme deficiencies (e.g., Wilson’s, Hemochromatosis, Glycogen storage diseases) are **Autosomal Recessive**. * **Achondroplasia Key Features:** Rhizomelic (proximal) shortening of limbs, trident hand, frontal bossing, and normal intelligence/life expectancy [1]. * **Advanced Paternal Age:** Strongly linked to *de novo* AD mutations like Achondroplasia and Apert syndrome.

Question 160: What is the commonest mode of inheritance among diseases with Mendelian inheritance?

A. Autosomal dominant (Correct Answer)
B. Autosomal recessive
C. X-linked recessive
D. X-linked dominant

Explanation: **Explanation:** **Why Autosomal Dominant is Correct:** Autosomal dominant (AD) inheritance is the most common mode of inheritance among Mendelian disorders. This is primarily because a mutation in only one allele (heterozygous state) is sufficient to manifest the disease. AD disorders often involve mutations in **structural proteins** (e.g., Collagen in Osteogenesis Imperfecta) or **regulatory proteins/receptors** (e.g., LDL receptor in Familial Hypercholesterolemia). Because these conditions often have a delayed age of onset (post-reproductive age), the mutated genes persist in the population gene pool more effectively than severe childhood recessive conditions [1]. **Analysis of Incorrect Options:** * **Autosomal Recessive (AR):** These are the second most common. They typically require two copies of the mutated gene (homozygous) to manifest. AR disorders usually involve **enzymatic deficiencies** (e.g., Phenylketonuria, Alkaptonuria). * **X-linked Recessive (XLR):** These are less common as they primarily affect males. Females are usually asymptomatic carriers unless skewed lyonization occurs. Examples include Hemophilia A and Duchenne Muscular Dystrophy. * **X-linked Dominant (XLD):** This is the rarest Mendelian inheritance pattern. Both males and females are affected, but it is often lethal in males (e.g., Rett Syndrome, Vitamin D-resistant rickets). **High-Yield Clinical Pearls for NEET-PG:** * **Vertical Transmission:** AD disorders show vertical inheritance (seen in every generation). * **Horizontal Transmission:** AR disorders often show horizontal inheritance (seen in siblings but not parents). * **New Mutations:** Many AD cases (like Achondroplasia) arise from *de novo* mutations associated with advanced paternal age [1]. * **Key Concept:** If a question asks for the most common inheritance pattern for **enzymopathies**, the answer is **Autosomal Recessive**. For **structural protein defects**, it is **Autosomal Dominant**.

Practice by Chapter

Principles of Medical Genetics

Practice Questions

Genetic Testing and Counseling

Practice Questions

Single Gene Disorders

Practice Questions

Chromosomal Disorders

Practice Questions

Mitochondrial Diseases

Practice Questions

Pharmacogenomics

Practice Questions

Cancer Genetics

Practice Questions

Genetics of Common Diseases

Practice Questions

Epigenetics and Disease

Practice Questions

Genetic Basis of Developmental Disorders

Practice Questions

Ethical Issues in Medical Genetics

Practice Questions

Gene Therapy and Precision Medicine

Practice Questions

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free