Genetics and Disease Practice Questions

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.

Q: A teenage boy, who was previously raised as a girl, presents with primary amenorrhea and lack of secondary sexual characteristics. On examination, he has tall stature, small testes, and gynecomastia. Which of the following is the most likely genotype?

47,XXY. ***Correct: 47,XXY (Klinefelter Syndrome)*** - This patient presents with **classic features of Klinefelter syndrome**: tall stature, small firm testes, gynecomastia, and hypogonadism [1]. - The **47,XXY karyotype** results from meiotic nondisjunction leading to an extra X chromosome. - **Hypogonadism** causes decreased testosterone, leading to lack of secondary sexual characteristics and increased FSH/LH [1]. - Patients typically have **eunuchoid body proportions** (tall stature with long limbs) due to delayed epiphyseal closure [1]. - The presence of **gynecomastia** is due to relative estrogen excess compared to testosterone [1]. - Primary amenorrhea mentioned here likely refers to the lack of pubertal development (developmental delay). *Incorrect: 47,XYY (Supermale Syndrome)* - These individuals are **tall males with normal virilization** and normal-sized testes - No gynecomastia or hypogonadism - Often associated with learning difficulties but normal sexual development *Incorrect: 45,X (Turner Syndrome)* - Presents in **phenotypic females** with **short stature** (not tall) [2]. - Features include webbed neck, shield chest, coarctation of aorta - Primary amenorrhea present but patient would be raised as female throughout - Does not explain male phenotype or gynecomastia in this case *Incorrect: 46,XX (Normal Female Karyotype)* - Normal female karyotype would not explain **male phenotype** with testes - Does not account for gynecomastia or the clinical presentation described

Q: Which of the following genetic mutations is most commonly associated with familial cases of Amyotrophic Lateral Sclerosis (ALS)?

SOD1 gene mutation. ***SOD1 gene mutation***- Mutations in the **Superoxide Dismutase 1 (SOD1)** gene are historically significant and account for approximately 15–20% of all familial ALS cases.- The SOD1 protein is located in the cytoplasm and mitochondria, and mutations lead to toxic misfolding and aggregation, resulting in **motor neuron death**.*CFTR gene mutation*- The **CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)** gene mutation is critically linked to the development of **Cystic Fibrosis**, a severe disorder of exocrine glands.- This mutation primarily affects chloride ion transport across epithelia, leading to highly viscous secretions, particularly in the airways and pancreas, not motor neuron disease.*HTT gene mutation*- Mutations involving the **HTT (Huntingtin)** gene, specifically expanded **CAG trinucleotide repeats**, cause **Huntington's disease**.- Huntington’s disease is characterized by progressive degeneration of the **striatum** and cortex, leading to movement abnormalities (*chorea*), cognitive decline, and psychiatric symptoms, distinct from ALS.*FMR1 gene mutation*- The **FMR1 (Fragile X Messenger Ribonucleoprotein 1)** gene is responsible for **Fragile X syndrome**, the most common inherited cause of intellectual disability.- The mutation involves expansion of the **CGG trinucleotide repeat**, typically leading to transcriptional silencing and symptoms like macroorchidism and behavioral issues, not primary motor neuron degeneration.

Q: The child is having skeletal abnormality in arms and hands. Which possible heart disease is seen in this condition?

ASD. ***ASD*** - The image shows a child with **phocomelia** or **hypoplastic radius/ulna**, a characteristic skeletal abnormality of the arms and hands, strongly associated with **Holt-Oram syndrome** - **Holt-Oram syndrome** is an **autosomal dominant** disorder caused by mutations in the **TBX5** gene, characterized by upper limb defects (absent/hypoplastic thumb, triphalangeal thumb, radial hypoplasia) and congenital heart defects - The most common cardiac defect is **ASD (ostium secundum type)**, followed by VSD — making ASD the correct answer *PDA* - **Patent ductus arteriosus (PDA)** is a common congenital heart defect but is **not specifically associated** with the upper limb skeletal abnormalities of Holt-Oram syndrome - PDA is classically seen in **premature infants** or associated with **rubella** infection, without specific upper limb skeletal anomalies *VSD* - **Ventricular septal defect (VSD)** is the **second most common** cardiac defect in Holt-Oram syndrome (after ASD), but it is less frequently associated than ASD - VSD is also the most common congenital heart defect overall, but without the specific upper limb skeletal findings, it would not be the first-line answer here *TOF* - **Tetralogy of Fallot (TOF)** comprises pulmonary stenosis, VSD, overriding aorta, and right ventricular hypertrophy - TOF is **not characteristically associated** with Holt-Oram syndrome or upper limb skeletal abnormalities; it is classically associated with cyanotic "tet spells" in infants

Q: The image reveals hyper-extensible skin seen with Ehlers-Danlos syndrome. Which of the following is commonly seen in Marfan syndrome?

Ectopia lentis. ***Ectopia lentis*** - **Ectopia lentis** (lens dislocation) is a hallmark ophthalmic feature of **Marfan syndrome**, occurring in 60-80% of patients, typically displaced superiorly and temporally. - This condition results from defects in the **fibrillin-1 gene (FBN1)**, which weakens the **zonular fibers** that suspend the lens, making it a major diagnostic criterion in the Ghent nosology. *Hyperextensible joints* - **Joint hypermobility** is more characteristic of **Ehlers-Danlos syndrome** than Marfan syndrome, where joint involvement is typically less pronounced. - While Marfan patients may have some joint laxity, the extreme **hyperextensibility** seen in Ehlers-Danlos is not a defining feature of Marfan syndrome. *Blue sclerae* - **Blue sclerae** are pathognomonic of **osteogenesis imperfecta**, caused by thin scleral collagen allowing the underlying choroid to show through. - This finding is not associated with **Marfan syndrome**, which primarily affects fibrillin-1 rather than type I collagen found in scleral tissue. *Easy bruising* - **Easy bruising** and bleeding tendencies are characteristic of **Ehlers-Danlos syndrome**, particularly the classical and hypermobile types. - Marfan syndrome does not typically cause **coagulation disorders** or **vascular fragility** that would lead to easy bruising patterns.

Question 1

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 2

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 3

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 4

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 5

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 6

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

Question 7

A teenage boy, who was previously raised as a girl, presents with primary amenorrhea and lack of secondary sexual characteristics. On examination, he has tall stature, small testes, and gynecomastia. Which of the following is the most likely genotype?

Accepted Answer

47,XXY

Answer

47,XYY

Answer

45,X

Answer

46,XX

Question 8

Which of the following genetic mutations is most commonly associated with familial cases of Amyotrophic Lateral Sclerosis (ALS)?

Accepted Answer

SOD1 gene mutation

Answer

HTT gene mutation

Answer

CFTR gene mutation

Answer

FMR1 gene mutation

Question 9

The child is having skeletal abnormality in arms and hands. Which possible heart disease is seen in this condition?

Accepted Answer

ASD

Answer

PDA

Answer

VSD

Answer

TOF

Question 10

The image reveals hyper-extensible skin seen with Ehlers-Danlos syndrome. Which of the following is commonly seen in Marfan syndrome?

Accepted Answer

Ectopia lentis

Answer

Hyperextensible joints

Answer

Easy bruising

Answer

Blue sclerae

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?