Genetics and Disease Practice Questions

Q: A 35-year-old nonsmoking male has been diagnosed with emphysema. His father died of emphysema at age 30, but he smoked. His father also had cirrhosis and recurrent pancreatitis but did not drink alcohol. Which one of the following inheritance patterns typifies this disease process?

Codominant. The clinical presentation of early-onset emphysema in a non-smoker, combined with a family history of cirrhosis and pancreatitis, is classic for **Alpha-1 Antitrypsin (AAT) Deficiency**. **Why Codominant is Correct:** The inheritance of AAT deficiency is characterized by **codominance**. The *SERPINA1* gene has several alleles (M, S, and Z). In a codominant pattern, both alleles in a heterozygote are expressed equally, contributing to the overall phenotype. * **PiMM:** Normal levels of AAT. * **PiMZ:** Heterozygous; intermediate levels (increased risk if smoking). * **PiZZ:** Homozygous; severely low levels, leading to panacinar emphysema and liver cirrhosis (due to misfolding and accumulation of the protein in hepatocytes) [2]. **Why Incorrect Options are Wrong:** * **Autosomal Dominant:** In AD, one mutant allele masks the normal one. Here, the normal allele (M) still produces functional protein, so the phenotype depends on the specific combination of both alleles [1]. * **Incomplete Dominance:** This would imply a "blending" of traits where the phenotype is an intermediate between the two parents. In AAT deficiency, both gene products are distinctly present and measurable. * **Autosomal Recessive:** While the *disease* often manifests when two abnormal alleles are present (like ZZ), the *inheritance pattern* of the alleles themselves is codominant because both alleles contribute to the serum protein level. **High-Yield Clinical Pearls for NEET-PG:** * **Pathology:** Emphysema in AAT deficiency is **Panacinar** (lower lobes), whereas smoking-related emphysema is **Centriacinar** (upper lobes). * **Liver Involvement:** PAS-positive, diastase-resistant globules in hepatocytes are pathognomonic [1]. * **Diagnosis:** Initial screening is via serum AAT levels; gold standard is phenotyping (isoelectric focusing). * **Associated Condition:** Panniculitis (necrotizing skin lesions) is a rare but high-yield association.

Q: Adult Polycystic kidney disease is inherited by which mode?

Autosomal dominant. **Autosomal Dominant Polycystic Kidney Disease (ADPKD)** is the most common hereditary kidney disease [1]. It is inherited in an **Autosomal Dominant** pattern, meaning a single copy of the mutated gene from one parent is sufficient to cause the disease [1]. * **Why Option A is correct:** ADPKD is primarily caused by mutations in the **PKD1** gene (85% of cases, located on Chromosome 16) or the **PKD2** gene (15% of cases, located on Chromosome 4) [1]. It typically presents in the 3rd to 5th decade of life with bilateral renal cysts, hypertension, and hematuria [1]. * **Why Options B, C, and D are incorrect:** * **Autosomal Recessive (ARPKD):** This is a distinct, rarer entity caused by mutations in the *PKHD1* gene. It typically presents in infancy or childhood and is associated with congenital hepatic fibrosis. * **X-linked/Mitochondrial:** These modes of inheritance are not associated with the classic presentation of polycystic kidney disease. **High-Yield Clinical Pearls for NEET-PG:** 1. **Extra-renal manifestations:** The most common is **Liver cysts**. The most life-threatening is **Berry Aneurysms** (Circle of Willis), which can lead to subarachnoid hemorrhage. Other features include mitral valve prolapse and diverticulosis. 2. **Diagnosis:** Ultrasonography is the primary screening tool. Diagnosis is based on the number of cysts relative to the patient's age (Ravine criteria). 3. **Prognosis:** PKD1 mutations progress to End-Stage Renal Disease (ESRD) earlier (mean age ~54) compared to PKD2 (mean age ~74) [1]. 4. **Treatment:** Tolvaptan (a V2-receptor antagonist) is used to slow the progression of cyst growth and renal decline.

Q: Which of the following is NOT a common tumor associated with neurofibromatosis?

Retinoblastoma. **Explanation:** **Neurofibromatosis (NF)** is a group of autosomal dominant neurocutaneous syndromes (phakomatoses) characterized by a high predisposition to tumors of the central and peripheral nervous systems. **Why Retinoblastoma is the Correct Answer:** Retinoblastoma is caused by a mutation in the **RB1 gene** on chromosome 13. It is not associated with Neurofibromatosis Type 1 (NF1) or Type 2 (NF2). While NF1 is associated with ocular findings like **Lisch nodules** and **Optic Nerve Gliomas**, it does not increase the risk for retinoblastoma. **Analysis of Incorrect Options:** * **A. Gliomas:** These are highly characteristic of **NF1**. Specifically, **Optic Pathway Gliomas** (pilocytic astrocytomas) occur in up to 15% of NF1 patients. * **C. Schwannomas:** These are the hallmark of **NF2**. The classic presentation is **bilateral vestibular schwannomas** (acoustic neuromas) [1]. NF2 is often remembered by the mnemonic "MISME" (Multiple Inherited Schwannomas, Meningiomas, and Ependymomas). * **D. Meningiomas:** These are common intracranial tumors associated with **NF2**. Patients with NF2 often develop multiple meningiomas at a younger age than the general population. **High-Yield Clinical Pearls for NEET-PG:** * **NF1 (von Recklinghausen Disease):** Chromosome **17** (Protein: Neurofibromin). Key features: Café-au-lait spots, Lisch nodules (iris hamartomas), Axillary freckling (Crowe sign), and Neurofibromas. * **NF2:** Chromosome **22** (Protein: Merlin/Schwannomin). Key features: Bilateral acoustic neuromas [1], cataracts (juvenile posterior subcapsular lenticular opacities), and meningiomas. * **Rule of 2s for NF2:** Chromosome **22**, Bilateral (2) Eighth (2x4) nerve tumors.

Q: Complications of Wilson's disease include all except?

Peripheral neuropathy. Wilson’s Disease (Hepatolenticular degeneration) is an autosomal recessive disorder caused by mutations in the **ATP7B gene**, leading to impaired biliary copper excretion and systemic copper accumulation. **Why Peripheral Neuropathy is the correct answer:** While Wilson’s disease causes significant neurological damage, it primarily affects the **Central Nervous System (CNS)**, specifically the basal ganglia [1]. **Peripheral neuropathy is not a feature** of Wilson’s disease. In fact, if a patient with Wilson’s disease develops peripheral neuropathy, it is usually an adverse effect of treatment with **D-penicillamine** (which can cause Vitamin B6 deficiency). **Analysis of Incorrect Options:** * **Fanconi Syndrome:** Excess copper is toxic to the renal proximal convoluted tubules, leading to Type 2 Renal Tubular Acidosis (Fanconi syndrome), characterized by glucosuria, aminoaciduria, and phosphaturia [1]. * **Ataxia:** Copper deposition in the cerebellum and its pathways leads to cerebellar signs, including ataxia, dysarthria, and coordination deficits [1]. * **Hemolytic Anemia:** Sudden release of free copper into the bloodstream from necrotic hepatocytes causes oxidative stress to RBCs (Coombs-negative hemolytic anemia), often seen during a "Wilsonian crisis" [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Kayser-Fleischer (KF) Rings:** Copper deposition in the **Descemet’s membrane** of the cornea (best seen on slit-lamp exam). * **Diagnosis:** Low serum Ceruloplasmin (<20 mg/dL), increased 24-hour urinary copper excretion, and "Giant Panda" sign on MRI Brain. * **Treatment:** Chelators like **Trientine** (preferred) or D-penicillamine; Zinc is used for maintenance as it inhibits intestinal copper absorption.

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

Tuberous sclerosis. **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.

Q: 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?

Autosomal dominant. 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].

Q: Which of the following is NOT a mitochondrial disease?

Spino-cerebellar ataxia. 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).

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

Neurofibromatosis. **Explanation:** **Neurofibromatosis (NF)** is the correct answer as both NF Type 1 (von Recklinghausen disease) and NF Type 2 are classic examples of **Autosomal Dominant (AD)** inheritance. NF1 is caused by a mutation in the *NF1* gene on chromosome 17, while NF2 involves the *NF2* gene on chromosome 22. A key feature of AD inheritance seen in NF is **high penetrance but variable expressivity**, meaning almost everyone with the mutation shows signs, but the severity varies significantly. **Analysis of Incorrect Options:** * **G6PD Deficiency:** This is an **X-linked recessive** disorder. It primarily affects males, causing episodic hemolysis triggered by oxidative stress (e.g., fava beans, primaquine). * **Hirschsprung Disease:** This condition exhibits **complex/multifactorial inheritance**. While associated with mutations in the *RET* proto-oncogene, it does not follow a simple Mendelian AD pattern and often shows variable penetrance. * **Vitamin D Resistant Rickets (Hereditary Hypophosphatemic Rickets):** This is the classic example of **X-linked Dominant** inheritance. It is characterized by phosphate wasting in the kidneys. **High-Yield Clinical Pearls for NEET-PG:** * **NF1 Mnemonic:** "17 letters in von Recklinghausen" = Chromosome **17**. Look for Lisch nodules, Café-au-lait spots, and optic gliomas. * **NF2 Mnemonic:** "22" = Chromosome **22**. Look for bilateral acoustic neuromas (vestibular schwannomas) [1]. * **AD Inheritance Rule:** Usually involves mutations in **structural proteins** (e.g., Collagen, Fibrillin) or **receptors**, whereas Autosomal Recessive conditions usually involve **enzyme deficiencies**.

Q: A 32-year-old woman presents with a 2-day history of decreased vision and photopsia in her left eye. She is noted to be unusually tall with long limbs and slender fingers. Physical examination reveals pectus excavatum, kyphoscoliosis, a midsystolic click, and a pansystolic murmur. Ophthalmologic examination shows a retinal detachment and lens dislocation. The patient is at greatest risk for which of the following conditions?

Ascending aortic aneurysm. ### Explanation The clinical presentation is classic for **Marfan Syndrome**, an autosomal dominant disorder caused by a mutation in the **FBN1 gene** on chromosome 15, which encodes **fibrillin-1** [1]. This protein is essential for the structural integrity of the extracellular matrix and the regulation of TGF-β. **Why the correct answer is right:** The patient exhibits the characteristic triad of Marfan Syndrome: 1. **Skeletal:** Tall stature, arachnodactyly (slender fingers), pectus excavatum, and kyphoscoliosis. 2. **Ocular:** Ectopia lentis (typically **superotemporal** dislocation) and retinal detachment. 3. **Cardiovascular:** Mitral valve prolapse (midsystolic click/pansystolic murmur). The most life-threatening complication and the leading cause of mortality in these patients is **cystic medial necrosis** of the aorta, leading to **ascending aortic aneurysm**, dissection, or rupture [1]. **Why the incorrect options are wrong:** * **A. Hearing loss:** Associated with Alport syndrome or Osteogenesis Imperfecta, not Marfan. * **B. Gout:** Associated with Lesch-Nyhan syndrome or lead poisoning; no direct link to Marfan. * **D. Rupture of the large intestine:** This is a characteristic complication of **Vascular Ehlers-Danlos Syndrome (Type IV)**, caused by defects in Type III collagen (COL3A1) [2]. While EDS shares some features with Marfan, intestinal rupture is not typical for Marfan [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Lens Dislocation:** Marfan = **Upward** (Superotemporal); Homocystinuria = **Downward** (Inferonasal). * **Steinberg Sign:** Thumb projects beyond the ulnar border of the clenched fist. * **Walker-Murdoch Sign:** Thumb and pinky overlap when encircling the opposite wrist. * **Management:** Beta-blockers or ARBs (Losartan) are used to slow the rate of aortic root dilation by decreasing TGF-β signaling and blood pressure.

Question 1

A 35-year-old nonsmoking male has been diagnosed with emphysema. His father died of emphysema at age 30, but he smoked. His father also had cirrhosis and recurrent pancreatitis but did not drink alcohol. Which one of the following inheritance patterns typifies this disease process?

Accepted Answer

Codominant

Answer

Autosomal dominant

Answer

Incomplete dominance

Answer

Autosomal recessive

Question 2

Adult Polycystic kidney disease is inherited by which mode?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X linked

Answer

Mitochondrial

Question 3

Which of the following is NOT a common tumor associated with neurofibromatosis?

Accepted Answer

Retinoblastoma

Answer

Gliomas

Answer

Schwannomas

Answer

Meningiomas

Question 4

Complications of Wilson's disease include all except?

Accepted Answer

Peripheral neuropathy

Answer

Fanconi syndrome

Answer

Ataxia

Answer

Hemolytic anemia

Question 5

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

Accepted Answer

Tuberous sclerosis

Answer

Color blindness

Answer

Hemophilia

Answer

Phenylketonuria

Question 6

What is the most common sign in mitochondrial inheritance diseases?

Accepted Answer

External ophthalmoplegia

Answer

Ataxia

Answer

Psychosis

Answer

Neurogenic weakness

Question 7

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?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked recessive

Answer

X-linked dominant

Question 8

Which of the following is NOT a mitochondrial disease?

Accepted Answer

Spino-cerebellar ataxia

Answer

Leber's hereditary optic neuropathy

Answer

Kearns-Sayre syndrome

Answer

Progressive external ophthalmoplegia

Question 9

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

Accepted Answer

Neurofibromatosis

Answer

G6PD deficiency

Answer

Hirschsprung disease

Answer

Vitamin D resistant rickets

Question 10

A 32-year-old woman presents with a 2-day history of decreased vision and photopsia in her left eye. She is noted to be unusually tall with long limbs and slender fingers. Physical examination reveals pectus excavatum, kyphoscoliosis, a midsystolic click, and a pansystolic murmur. Ophthalmologic examination shows a retinal detachment and lens dislocation. The patient is at greatest risk for which of the following conditions?

Accepted Answer

Ascending aortic aneurysm

Answer

Hearing loss

Answer

Gout

Answer

Rupture of the large intestine

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?