Genetics and Disease Practice Questions

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.

Q: A very tall, slender 16-year-old boy is referred for evaluation of an abnormal CXR. He reports no pulmonary or cardiac symptoms and feels well. On physical examination, he has long fingers, pectus excavatum, and a high arched palate. Which of the following is most likely to be seen on his CXR?

Aortic dilatation. The clinical presentation of a tall, slender adolescent with long fingers (arachnodactyly), pectus excavatum, and a high arched palate is classic for **Marfan Syndrome**, an autosomal dominant disorder caused by a mutation in the **FBN1 gene** (encoding Fibrillin-1) [1]. **Why Aortic Dilatation is Correct:** The most common and life-threatening cardiovascular manifestation of Marfan syndrome is **cystic medial necrosis** of the aorta [1]. This leads to progressive **aortic root dilatation**, which can be visualized on a Chest X-ray (CXR) as a widened mediastinum or an enlarged aortic knob. It is the most likely finding among the choices given the high prevalence of cardiovascular involvement (up to 80%) in these patients. **Why Other Options are Incorrect:** * **A. Dextrocardia:** This is associated with Kartagener Syndrome (Situs Inversus), not Marfan Syndrome. * **C. Pneumothorax:** While patients with Marfan syndrome are at an increased risk for spontaneous pneumothorax due to subapical blebs, aortic root dilatation is a more characteristic and frequent finding associated with the syndrome's core pathology. * **D. Apical interstitial fibrosis:** This is a classic feature of Ankylosing Spondylitis, not Marfan Syndrome. **NEET-PG High-Yield Pearls:** * **Genetics:** FBN1 mutation on **Chromosome 15** [1]. * **Ocular:** **Ectopia lentis** (upward and outward lens subluxation) is a hallmark. * **Cardiac:** Aortic root dilatation and **Mitral Valve Prolapse (MVP)** are the most common findings. * **Diagnosis:** Based on the **Ghent Criteria**. * **Management:** Beta-blockers or ARBs (Losartan) are used to slow aortic dilatation; surgery is indicated if the aortic diameter exceeds 5 cm.

Q: A 20-year-old female on oral contraceptive pills presents with behavioral changes and abdominal pain. What is the most probable diagnosis?

Acute intermittent porphyria. The clinical presentation of **Acute Intermittent Porphyria (AIP)** is classically described by the "5 Ps": **P**ainful abdomen, **P**sychological disturbances (behavioral changes), **P**olyneuropathy, **P**urple urine, and **P**recipitated by drugs [1]. **Why AIP is the correct answer:** AIP is an autosomal dominant metabolic disorder caused by a deficiency of the enzyme **Porphobilinogen (PBG) deaminase**. The symptoms are triggered by factors that induce the enzyme **ALA synthase**, leading to an accumulation of toxic heme precursors (ALA and PBG). **Oral Contraceptive Pills (OCPs)**, specifically the progesterone component, are potent inducers of the cytochrome P450 system and ALA synthase, making them a classic trigger for acute attacks in susceptible females [1]. **Why other options are incorrect:** * **Pancreatitis:** While it causes severe abdominal pain, it is not typically associated with acute behavioral changes or triggered specifically by OCPs (unless OCP-induced hypertriglyceridemia is present, which is less common in a 20-year-old). * **Aortic Aneurysm:** Extremely rare in a 20-year-old female and does not explain the psychiatric symptoms. * **SLE:** While SLE can cause abdominal pain (vasculitis) and psychosis (lupus cerebritis), the acute onset triggered by OCPs more specifically points toward a metabolic porphyric crisis. **High-Yield Clinical Pearls for NEET-PG:** * **Diagnosis:** Elevated urinary **PBG** levels during an attack (Screening: Hoesch test/Watson-Schwartz test). * **Management:** Intravenous **Hemin** (suppresses ALA synthase) and **10% Dextrose** (glucose inhibits ALA synthase). * **Key Trigger Drugs:** Barbiturates, Sulfonamides, Griseofulvin, and Alcohol. * **Note:** Unlike other porphyrias, AIP has **no cutaneous manifestations** (no photosensitivity).

Q: A female child presents with virilization and hypertension with low plasma renin. What is the most likely diagnosis?

11 beta hydroxylase deficiency. The clinical presentation of **virilization** (ambiguous genitalia/androgen excess) combined with **hypertension** and **low renin** is the classic hallmark of **11β-hydroxylase deficiency**. [1] **1. Why 11β-hydroxylase deficiency is correct:** In this condition, the enzyme 11β-hydroxylase is deficient, blocking the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone (DOC) to corticosterone. This leads to: * **Androgen Excess:** Shunting of precursors into the androgen pathway causes virilization in females. [1] * **Hypertension:** The block leads to an accumulation of **11-deoxycorticosterone (DOC)**. DOC is a potent mineralocorticoid; its excess causes sodium retention and volume expansion, resulting in hypertension and feedback suppression of **Renin**. [1] **2. Why other options are incorrect:** * **21α-hydroxylase deficiency:** This is the most common cause of CAH. While it causes virilization, it leads to **hypotension** and "salt-wasting" because mineralocorticoids (aldosterone) cannot be produced. * **3β-hydroxysteroid dehydrogenase deficiency:** This rare form results in a lack of all adrenal steroids (glucocorticoids, mineralocorticoids, and sex steroids). It typically presents with salt-wasting and ambiguous genitalia in males (incomplete masculinization). * **Conn’s Syndrome:** While it presents with hypertension and low renin (primary hyperaldosteronism), it **does not cause virilization** as it involves only the zona glomerulosa. **High-Yield Clinical Pearls for NEET-PG:** * **11β-hydroxylase deficiency:** Hypertension + Virilization (The "1" in 11 stands for "Hypertension"). [1] * **21α-hydroxylase deficiency:** Hypotension + Virilization. [1] * **17α-hydroxylase deficiency:** Hypertension + No Virilization (Delayed puberty/Sexual infantilism). * **Key Marker:** Elevated **11-deoxycortisol** and **11-deoxycorticosterone** are diagnostic for 11β-hydroxylase deficiency.

Q: Which of the following is NOT a characteristic of Xeroderma Pigmentosum?

It is an autosomal recessive disorder.. The question asks for the statement that is **NOT** a characteristic of Xeroderma Pigmentosum (XP). However, based on medical facts, **Option A is actually a true characteristic** of the disease. In the context of this question, there appears to be a technical error in the provided key, as all four options (A, B, C, and D) are scientifically correct descriptions of XP. ### **Medical Explanation** 1. **Why Option A is a characteristic:** Xeroderma Pigmentosum is a classic **autosomal recessive** genetic disorder [1]. It occurs when a child inherits two mutated copies of the XP genes (XPA through XPG). 2. **Why Option B is a characteristic:** The fundamental pathology is a **defect in Nucleotide Excision Repair (NER)** [1]. This system is responsible for "cutting out" DNA segments damaged by environmental factors. 3. **Why Option C is a characteristic:** Due to the inability to repair DNA, patients have a >1000-fold increased risk of cutaneous malignancies, including **Squamous Cell Carcinoma (SCC)**, Basal Cell Carcinoma (BCC), and Melanoma. 4. **Why Option D is a characteristic:** UV radiation (specifically UV-B) causes the formation of **pyrimidine dimers (thymine dimers)**. In healthy individuals, NER fixes these; in XP patients, they persist, leading to mutations and carcinogenesis. ### **High-Yield Clinical Pearls for NEET-PG** * **Early Sign:** Severe "sunburn" after minimal sun exposure and extensive freckling (lentigines) before age 2. * **Neurological Involvement:** About 20-30% of patients (e.g., De Sanctis-Cacchione syndrome) show progressive neurodegeneration and sensorineural deafness. * **Ocular Findings:** Photophobia, keratitis, and corneal opacification are common. * **Management:** Strict UV protection (sunscreen, protective clothing) and regular dermatological surveillance.

Q: In a family, the father has widely spaced eyes, increased facial hair, and deafness. One of the three children has deafness with similar facial features. The mother is normal. Which one of the following is the most likely pattern of inheritance in this case?

Autosomal dominant. **Explanation:** The clinical presentation described—widely spaced eyes (telecanthus), synophrys (increased facial hair/unibrow), and sensorineural deafness—is characteristic of **Waardenburg Syndrome**. **1. Why Autosomal Dominant (AD) is correct:** In this scenario, the condition is transmitted directly from an affected father to his child. This represents **vertical transmission** (seen in every generation). Since the mother is normal and the trait appears in the offspring, it indicates that a single copy of the mutant allele from the father is sufficient to cause the phenotype. This is the hallmark of Autosomal Dominant inheritance. **2. Why other options are incorrect:** * **Autosomal Recessive (AR):** This typically presents with **horizontal transmission** (skipped generations). For a child to be affected, both parents must usually be carriers. If the mother is "normal" (not a carrier), an AR condition would not manifest in the child. * **X-linked Dominant (XLD):** While an affected father can pass an XLD trait to his daughters, he **cannot** pass it to his sons (as he gives them a Y chromosome). The question mentions "one of three children" without specifying gender; however, AD is the more common and classic fit for Waardenburg Syndrome (Type 1 and 2). * **X-linked Recessive (XLR):** An affected father would pass the gene to all daughters (making them carriers) but none of his children would typically be affected unless the mother was also a carrier. **Clinical Pearls for NEET-PG:** * **Waardenburg Syndrome:** Look for "White forelock" (poliosis), heterochromia iridis (different colored eyes), and sensorineural hearing loss. * **High-Yield Rule:** Vertical transmission + Male-to-Male transmission = **Autosomal Dominant**. * **Mnemonic:** Most structural protein defects are AD; most enzyme deficiencies are AR.

Question 1

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 2

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 3

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 4

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

Question 5

A very tall, slender 16-year-old boy is referred for evaluation of an abnormal CXR. He reports no pulmonary or cardiac symptoms and feels well. On physical examination, he has long fingers, pectus excavatum, and a high arched palate. Which of the following is most likely to be seen on his CXR?

Accepted Answer

Aortic dilatation

Answer

Dextrocardia

Answer

Pneumothorax

Answer

Apical interstitial fibrosis

Question 6

A 32-year-old man presents for routine evaluation. He has no symptoms but has noticed some new "nodules" on his legs. Physical examination reveals lumps on his Achilles tendon, yellow lesions around his eyes, and pigmentation of his iris. Which of the following is the most likely diagnosis?

Accepted Answer

Familial hyperlipidemia

Answer

Diabetes

Answer

Myxedema

Answer

Chronic renal disease

Question 7

A 20-year-old female on oral contraceptive pills presents with behavioral changes and abdominal pain. What is the most probable diagnosis?

Accepted Answer

Acute intermittent porphyria

Answer

Pancreatitis

Answer

Aortic aneurysm

Answer

Systemic Lupus Erythematosus (SLE)

Question 8

A female child presents with virilization and hypertension with low plasma renin. What is the most likely diagnosis?

Accepted Answer

11 beta hydroxylase deficiency

Answer

21 alpha hydroxylase deficiency

Answer

3 beta hydroxylase deficiency

Answer

Conn's syndrome

Question 9

Which of the following is NOT a characteristic of Xeroderma Pigmentosum?

Accepted Answer

It is an autosomal recessive disorder.

Answer

It is caused by defective DNA repair.

Answer

It is associated with an increased risk of squamous cell carcinoma.

Answer

Exposure to ultraviolet radiation can lead to the formation of thymine dimers.

Question 10

In a family, the father has widely spaced eyes, increased facial hair, and deafness. One of the three children has deafness with similar facial features. The mother is normal. Which one of the following is the most likely pattern of inheritance in this case?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

X-linked recessive

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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