Genetics and Disease Practice Questions

Q: A patient with parathyroid hyperplasia, pancreatic neuroendocrine tumor, and recurrent peptic ulcer disease most commonly has mutation of which gene?

MEN1 (menin gene). ***MEN1 (menin gene)*** - This patient presents with the classic triad of **Multiple Endocrine Neoplasia type 1 (MEN1)** syndrome: **primary hyperparathyroidism** (due to hyperplasia), **pancreatic neuroendocrine tumors** (such as gastrinomas causing ZES), and **pituitary adenomas**. - The MEN1 condition is caused by a germline mutation in the **MEN1 tumor suppressor gene**, which encodes the protein **menin**. *RET* - Mutations in the **RET proto-oncogene** are characteristically associated with **Multiple Endocrine Neoplasia type 2 (MEN2A and MEN2B)**. - MEN2 conditions typically involve **medullary thyroid carcinoma**, **pheochromocytoma**, and **parathyroid hyperplasia** (in MEN2A), rather than the pancreatic/gastrinoma presentation described. *TP53* - Mutations in the **TP53 tumor suppressor gene** are pathognomonic for **Li-Fraumeni syndrome**. - This syndrome is characterized by a high predisposition to a wide variety of early-onset malignancies, such as **sarcomas**, breast cancer, and adrenal cortical carcinomas, not the endocrine triad described. *VHL* - Mutations in the **von Hippel-Lindau (VHL) gene** are responsible for **VHL syndrome**. - This disorder is marked by **hemangioblastomas**, **renal cell carcinoma**, and **pheochromocytomas**, which do not correlate with the patient's presentation of hyperparathyroidism and peptic ulcer disease.

Q: A 17-year-old boy presents with gradually progressive muscle weakness predominantly involving the proximal muscles of the lower limbs. He has difficulty climbing stairs and getting up from a squatting position. There is a significant family history and his elder brother had similar complaints and died around the age of 40 years. Based on the age of onset, pattern of inheritance, and survival, what is the most likely diagnosis?

BMD. ***Becker Muscular Dystrophy (BMD)*** - BMD is an **X-linked recessive** disorder characterized by a mutation (typically a deletion) in the **dystrophin gene** that results in the production of a truncated, partially functional protein rather than the complete absence seen in Duchenne. - The onset is typically in late childhood or adolescence with a slower progression of **proximal muscle weakness**, allowing patients to remain ambulatory into adulthood and live significantly longer than those with Duchenne Muscular Dystrophy. *Duchenne Muscular Dystrophy (DMD)* - DMD typically presents much earlier, often between **ages 2 and 5**, with severe muscle weakness resulting in the loss of ambulation before age 12-13. - It is caused by the complete absence of **dystrophin**, leading to a more severe and rapidly progressive clinical course than BMD, with life expectancy significantly shorter than 40 years without advanced care. *Charcot-Marie-Tooth (CMT)* - CMT is a group of **hereditary neuropathies** that primarily present with distal muscle wasting,

Q: A patient presents with ataxia, ichthyosis, retinitis pigmentosa, and cardiac conduction defects. Laboratory evaluation reveals increased phytanic acid levels. What is the most likely diagnosis?

Refsum disease. ***Refsum disease*** - Caused by a deficiency of **peroxisomal phytanoyl-CoA hydroxylase**, leading to the accumulation of **phytanic acid**, which is toxic to the nervous system. - The classic clinical tetrad includes **ataxia**, **ichthyosis** (scaling of the skin), **retinitis pigmentosa** (causing night blindness), and **cardiac conduction defects** (arrhythmias). *Zellweger disease* - This is a severe peroxisome biogenesis disorder characterized by the **absence of functional peroxisomes** entirely rather than a specific enzyme defect. - Patients typically present with **craniofacial dysmorphism**, hypotonia, and seizures in early infancy with a much poorer prognosis. *Adrenoleukodystrophy* - Results from a mutation in the **ABCD1 gene**, leading to impaired beta-oxidation and the accumulation of **very-long-chain fatty acids (VLCFAs)**. - Clinical features primarily involve **adrenal insufficiency** (Addison disease) and progressive **neurological deterioration** rather than ichthyosis or elevated phytanic acid. *Metachromatic leukodystrophy* - Caused by a deficiency of **arylsulfatase A**, leading to the accumulation of **sulfatides** in the central and peripheral nervous system. - It is characterized by progressive **demyelination** leading to ataxia, dementia, and seizures, without the feature of elevated phytanic acid levels.

Q: A 10-year-old boy presents with excessive eating (hyperphagia) and obesity, with a BMI of 33. Genetic testing shows a deletion on chromosome 15. What is the most likely diagnosis?

Prader-Willi syndrome. ***Prader-Willi syndrome*** - This condition is caused by a **paternal deletion** of the **15q11-q13** region or **maternal uniparental disomy**, which is consistent with the described genetic finding. - The classic clinical presentation includes **hyperphagia**, leading to severe **obesity**, alongside **intellectual disability**, almond-shaped eyes, and hypogonadism. *Angelman syndrome* - While also involving the **15q11-q13** region, this is caused by a **maternal deletion** or **paternal uniparental disomy**. - Clinically, patients present with a **happy demeanor**, frequent laughter, ataxia, and seizures, rather than hyperphagia and obesity. *Rett syndrome* - An **X-linked dominant** disorder caused by mutations in the **MECP2 gene**, typically affecting females due to male lethality. - Characterized by the **loss of purposeful hand movements**, developmental regression, and **stereotypical hand-wringing** behaviors. *Down syndrome* - Caused by **trisomy 21**, not a deletion on chromosome 15. - Features include **distinctive facial dysmorphology**, such as **epicanthic folds** and a flat nasal bridge, along with congenital heart defects and varying degrees of intellectual impairment.

Q: Wilson's disease is inherited in which pattern?

Autosomal recessive. **Explanation:** Wilson’s disease (Hepatolenticular degeneration) is an **Autosomal Recessive (AR)** disorder caused by mutations in the **ATP7B gene** located on **Chromosome 13**. This gene encodes a P-type ATPase responsible for transporting copper into the bile for excretion and incorporating it into ceruloplasmin. A defect in this protein leads to toxic copper accumulation in the liver, brain (basal ganglia), and cornea [1]. **Analysis of Options:** * **Autosomal Recessive (Correct):** Most inborn errors of metabolism, including Wilson’s disease, Hemochromatosis, and Cystic Fibrosis, follow an AR pattern. Both parents must be carriers for a child to be affected (25% risk). * **Autosomal Dominant:** These disorders usually involve structural proteins (e.g., Marfan syndrome) or receptors (e.g., Familial Hypercholesterolemia). * **X-linked Recessive:** These typically affect males (e.g., Hemophilia, G6PD deficiency). Menkes disease, another copper metabolism disorder, is X-linked, which is a common point of confusion with Wilson's. * **X-linked Dominant:** Rare patterns seen in conditions like Alport syndrome or Vitamin D-resistant rickets. **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 increased hepatic copper content (Gold Standard). * **Treatment:** Chelating agents like **D-Penicillamine** (first-line historically) or Trientine. Oral **Zinc** is used for maintenance as it interferes with intestinal copper absorption. * **Neurological sign:** "Giant Panda Face" appearance on MRI midbrain [1].

Q: Which of the following is NOT an acute porphyria?

Porphyria cutanea tarda. Porphyrias are metabolic disorders caused by deficiencies in enzymes of the heme biosynthetic pathway. They are clinically classified into **Acute Porphyrias** (presenting with neurovisceral crises) and **Cutaneous Porphyrias** (presenting with skin photosensitivity) [1]. ### **Why Porphyria Cutanea Tarda (PCT) is the Correct Answer** PCT is the most common type of porphyria worldwide [1]. It is classified as a **chronic cutaneous porphyria**, not an acute one. It results from a deficiency of **Uroporphyrinogen decarboxylase (UROD)**. Clinically, it presents with skin fragility, blistering, and hyperpigmentation on sun-exposed areas (hands and face), often triggered by alcohol, iron overload, or Hepatitis C [1]. It does **not** cause the acute abdominal pain or neurological symptoms characteristic of acute porphyrias. ### **Analysis of Incorrect Options (Acute Porphyrias)** The following are classified as acute porphyrias because they involve the accumulation of neurotoxic precursors (ALA and PBG): * **Acute Intermittent Porphyria (AIP):** The most common acute porphyria. It presents with the "5 Ps": Painful abdomen, Polyneuropathy, Psychosis, Pink urine, and Precipitation by drugs [1]. * **Variegate Porphyria (VP) & Hereditary Coproporphyria (HCP):** These are "mixed" porphyrias. They are classified as acute because they cause neurovisceral crises, but they can also present with cutaneous photosensitivity. ### **NEET-PG High-Yield Pearls** * **Enzyme Deficiencies:** * AIP: Porphobilinogen deaminase (PBGD). * PCT: Uroporphyrinogen decarboxylase (UROD). * **Diagnosis:** The first-line screening test during an acute attack is checking for elevated **urinary Porphobilinogen (PBG)**. * **Management:** Acute attacks are treated with **IV Hemin** (suppresses ALA synthase) and high-dose glucose. * **Key Trigger:** Barbiturates and sulfonamides are notorious for precipitating acute attacks [1].

Q: Which of the following statements about hemochromatosis is false?

Leads to iron deposits in the testis. The correct answer is **C**. While Hereditary Hemochromatosis (HH) is a multi-system disorder of iron overload, the endocrine dysfunction involving the gonads is **not** primarily due to direct iron deposition in the testes [1]. Instead, it is caused by iron deposition in the **anterior pituitary gland**, leading to selective gonadotropin deficiency (Hypogonadotropic Hypogonadism) [1]. This results in secondary testicular atrophy, decreased libido, and impotence. **Analysis of other options:** * **Option A:** True. Most cases (approx. 85-90%) of classic HH are caused by a mutation in the **HFE gene** (most commonly the C282Y mutation) on Chromosome 6 [1]. * **Option B:** True. HH is inherited in an **autosomal recessive** pattern with variable penetrance [1]. * **Option D:** True. **Secondary hemochromatosis** occurs due to ineffective erythropoiesis (as seen in **Thalassemias** or Sideroblastic anemia) and chronic blood transfusions, leading to systemic iron overload despite a normal HFE gene. **NEET-PG High-Yield Pearls:** * **Classic Triad (Bronze Diabetes):** Cirrhosis, Diabetes Mellitus, and Skin Hyperpigmentation (occurs in late stages) [1]. * **Most Common Joint Involved:** Second and third metacarpophalangeal (MCP) joints (hook-like osteophytes). * **Cardiac Involvement:** Typically presents as Restrictive Cardiomyopathy (early) or Dilated Cardiomyopathy (late). * **Diagnosis:** Best initial screening test is **Transferrin Saturation** (>45%); Gold standard for HFE-HH is **Genetic Testing** [2]. * **Treatment:** Therapeutic phlebotomy is the mainstay of management [2].

Question 1

A patient with parathyroid hyperplasia, pancreatic neuroendocrine tumor, and recurrent peptic ulcer disease most commonly has mutation of which gene?

Accepted Answer

MEN1 (menin gene)

Answer

RET

Answer

TP53

Answer

VHL

Question 2

A 17-year-old boy presents with gradually progressive muscle weakness predominantly involving the proximal muscles of the lower limbs. He has difficulty climbing stairs and getting up from a squatting position. There is a significant family history and his elder brother had similar complaints and died around the age of 40 years. Based on the age of onset, pattern of inheritance, and survival, what is the most likely diagnosis?

Accepted Answer

BMD

Answer

DMD

Answer

CMT

Answer

ALS

Question 3

A patient presents with ataxia, ichthyosis, retinitis pigmentosa, and cardiac conduction defects. Laboratory evaluation reveals increased phytanic acid levels. What is the most likely diagnosis?

Accepted Answer

Refsum disease

Answer

Zellweger disease

Answer

Adrenoleukodystrophy

Answer

Metachromatic leukodystrophy

Question 4

A 10-year-old boy presents with excessive eating (hyperphagia) and obesity, with a BMI of 33.
Genetic testing shows a deletion on chromosome 15. What is the most likely diagnosis?

Accepted Answer

Prader-Willi syndrome

Answer

Angelman syndrome

Answer

Rett syndrome

Answer

Down syndrome

Question 5

A 22-year-old man presents with sudden loss of vision in his right eye. Physical examination reveals subluxation of the right crystalline lens. Auscultation of the chest reveals a midsystolic click. Echocardiography shows a floppy mitral valve and a dilated aortic arch. The patient's brother and cousin have similar symptoms. He has been prescribed a beta-blocker. A genetic defect involving which of the following substances is most likely present in this patient?

Accepted Answer

Fibrillin-1

Answer

Collagen

Answer

Dystrophin

Answer

NF1 protein

Question 6

In X-linked recessive (XLR) diseases, a modified inheritance pattern called 'pseudodominance' occurs when?

Accepted Answer

One parent is an unaffected heterozygote and the other is an affected homozygote.

Answer

One parent is an affected homozygote and the other is an unaffected homozygote.

Answer

One parent is normal and the other is an unaffected heterozygote.

Answer

Both parents are unaffected.

Question 7

Wilson's disease is inherited in which pattern?

Accepted Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X-linked recessive

Answer

X-linked dominant

Question 8

Which of the following is NOT an acute porphyria?

Accepted Answer

Porphyria cutanea tarda

Answer

Acute intermittent porphyria

Answer

Variegate porphyria

Answer

Hereditary coproporphyria

Question 9

Which of the following statements is TRUE regarding Duchenne muscular dystrophy?

Accepted Answer

There is a universal increase in creatine kinase.

Answer

It is autosomal dominant.

Answer

It has an onset in the second decade of life.

Answer

Cardiac muscle fibers are normal.

Question 10

Which of the following statements about hemochromatosis is false?

Accepted Answer

Leads to iron deposits in the testis

Answer

Caused by HFE gene mutation

Answer

Inherited in an autosomal recessive pattern

Answer

Secondary hemochromatosis can result from thalassemias

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?