Genetics and Disease Practice Questions

Q: Which of the following is NOT a feature of Marfan's syndrome?

Reduced joint mobility. Marfan’s syndrome is an autosomal dominant connective tissue disorder caused by a mutation in the **FBN1 gene** on chromosome 15, which encodes **fibrillin-1**. Fibrillin-1 is essential for the structural integrity of the extracellular matrix and the regulation of TGF-β. **Why "Reduced joint mobility" is the correct answer:** In Marfan’s syndrome, the defect in fibrillin leads to connective tissue laxity. Therefore, patients typically present with **joint hypermobility** (hyperextensibility), not reduced mobility. Reduced joint mobility and contractures are more characteristic of **Congenital Contractural Arachnodactyly (Beals Syndrome)**, which involves the FBN2 gene. **Analysis of incorrect options:** * **Arachnodactyly:** This refers to abnormally long, slender fingers ("spider-like"). It is a classic skeletal feature of Marfan’s, often assessed via the Walker-Murdoch (wrist) and Steinberg (thumb) signs. * **Dislocation of the lens (Ectopia lentis):** This occurs in ~60% of patients. Characteristically, the dislocation is **upward and outward (superior-temporal)** due to weakness in the ciliary zonules. * **Mitral regurgitation:** Cardiovascular complications are the leading cause of mortality. Mitral valve prolapse (MVP) leading to mitral regurgitation is common [1], alongside the more life-threatening **cystic medial necrosis** of the aorta, which leads to aortic root dilation and dissection. **High-Yield Clinical Pearls for NEET-PG:** * **Ghent Criteria:** Used for diagnosis (focuses on FBN1 mutation, Ectopia lentis, and Aortic root aneurysm). * **Arm span to Height ratio:** Typically >1.05 in Marfan’s. * **Homocystinuria vs. Marfan’s:** Both present with tall stature and ectopia lentis. However, Homocystinuria features **downward** lens dislocation, intellectual disability, and a prothrombotic state. * **Management:** Beta-blockers or ARBs (Losartan) are used to slow the rate of aortic root dilation.

Q: Which of the following statements about congenital adrenal hyperplasia is not true?

Hypokalemic alkalosis is seen.. **Explanation:** Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders characterized by a deficiency in enzymes required for cortisol synthesis [1]. **Why Option D is the correct answer (Not True):** In the most common form of CAH (21-hydroxylase deficiency), there is a lack of mineralocorticoids (aldosterone). This leads to "salt-wasting," characterized by **hyponatremia, hyperkalemia, and metabolic acidosis**. Therefore, the statement that "hypokalemic alkalosis is seen" is false. Hypokalemic alkalosis is instead characteristic of conditions with mineralocorticoid excess, such as Conn’s syndrome or 11-beta hydroxylase deficiency (where 11-deoxycorticosterone builds up). **Analysis of Incorrect Options:** * **Option A:** Correct. **21-alpha hydroxylase deficiency** accounts for >90% of CAH cases. * **Option B:** Correct. Excess androgens lead to **isosexual precocious puberty** in males (early development of secondary sexual characteristics but small testes). * **Option C:** Correct. In females, high levels of adrenal androgens in utero cause virilization, leading to **ambiguous genitalia** (clitoromegaly, labial fusion) at birth. **High-Yield Clinical Pearls for NEET-PG:** 1. **21-Hydroxylase Deficiency:** Most common; presents with salt-wasting, hypotension, and high **17-hydroxyprogesterone** levels [1]. 2. **11-Beta Hydroxylase Deficiency:** Second most common; presents with **hypertension** and hypokalemia due to the buildup of 11-deoxycorticosterone (DOC). 3. **17-Alpha Hydroxylase Deficiency:** Presents with hypertension but **delayed puberty/primary amenorrhea** (decreased sex hormones). 4. **Mnemonic:** If the enzyme starts with **1** (11, 17), it causes **HTN** (Hypertension). If the enzyme ends with **1** (11, 21), it causes **Virilization**.

Q: Which cardiac anomaly is commonly seen in Noonan's syndrome?

Pulmonary Stenosis. Explanation: Noonan’s syndrome is an autosomal dominant multisystem disorder, often referred to as the "Male Turner Syndrome" (though it affects both sexes). It is primarily caused by mutations in the **RAS-MAPK signaling pathway**, most commonly involving the **PTPN11 gene**. **Why Pulmonary Stenosis is Correct:** Congenital heart disease occurs in approximately 80% of patients with Noonan’s syndrome. The most characteristic lesion is **Valvular Pulmonary Stenosis (PS)**, often due to dysplastic pulmonary valves (seen in ~50% of cases). The second most common cardiac finding is **Hypertrophic Cardiomyopathy (HCM)**, specifically asymmetrical septal hypertrophy. **Analysis of Incorrect Options:** * **A. Ventricular Septal Defect (VSD):** While VSD can occur in many genetic syndromes (like Down syndrome), it is not the defining or most common lesion in Noonan’s. * **B. Atrial Septal Defect (ASD):** ASD (specifically Secundum type) is the second most common *structural* defect after PS in Noonan’s, but PS remains the classic "textbook" association for exams. * **D. Coarctation of the Aorta:** This is the classic cardiac association for **Turner Syndrome (45, XO)** [1]. Distinguishing Noonan’s (PS) from Turner’s (Coarctation/Bicuspid Aortic Valve) is a frequent high-yield NEET-PG pivot point. **High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** PTPN11 mutation (50% of cases). * **Phenotype:** Short stature, webbed neck, hypertelorism, and low-set ears (similar to Turner’s) [1]. * **Key Distinctions from Turner’s:** Noonan’s patients have **normal karyotypes**, can be male, and frequently present with **bleeding diathesis** (Factor XI deficiency) and **cryptorchidism**. * **Mnemonic:** **N**oonan = **N**orth (Pulmonary valve is "superior/north" to the Aortic valve).

Q: A 22-year-old patient presents with multiple neural tumors, pigmented iris hamartomas, and numerous tan macules on his skin. His father, paternal uncle, and paternal grandfather had a similar condition. What is the most likely diagnosis for this patient?

Neurofibromatosis type I. ### Explanation **Neurofibromatosis type I (NF1)**, also known as von Recklinghausen disease, is an **autosomal dominant** neurocutaneous syndrome caused by a mutation in the *NF1* gene on **chromosome 17**. The gene encodes **neurofibromin**, a tumor suppressor that negatively regulates the RAS pathway. The diagnosis is confirmed by the presence of classic clinical features described in the vignette: * **Tan macules:** These are **Café-au-lait spots** (usually ≥6 required for diagnosis). * **Pigmented iris hamartomas:** Known as **Lisch nodules**, which are pathognomonic for NF1. * **Multiple neural tumors:** These represent **neurofibromas** (cutaneous or plexiform). * **Family History:** The involvement of the father, uncle, and grandfather confirms an autosomal dominant inheritance pattern with high penetrance. **Analysis of Incorrect Options:** * **A. Ependymoma:** While associated with Neurofibromatosis type II (NF2), it is not a feature of NF1. NF2 is characterized by bilateral acoustic neuromas (schwannomas) and is linked to chromosome 22 [1]. * **B. Huntington disease:** An autosomal dominant neurodegenerative disorder characterized by chorea and dementia, caused by CAG triplet repeats on chromosome 4. It lacks cutaneous manifestations. * **C. Marfan syndrome:** A connective tissue disorder (FBN1 mutation) presenting with tall stature, ectopia lentis, and aortic root dilation, but not neural tumors or Lisch nodules. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for NF1:** "17 letters in von Recklinghausen" = **Chromosome 17**. * **Optic Glioma:** The most common CNS tumor associated with NF1. * **Skeletal Deformities:** Sphenoid wing dysplasia and pseudoarthrosis of the tibia are specific diagnostic criteria. * **Crowe Sign:** Axillary or inguinal freckling is a highly specific clinical sign for NF1.

Q: An 18-year-old patient presents with sebaceous cysts on the scalp and back of the neck, and an osteoma on the right mandible. Radiographs reveal multiple impacted supernumerary teeth in both jaws. These findings suggest which of the following conditions?

Gardner's syndrome. **Explanation** The clinical triad of **sebaceous (epidermoid) cysts**, **osteomas** (particularly of the mandible and skull), and **supernumerary teeth** is pathognomonic for **Gardner’s Syndrome**. **1. Why Gardner’s Syndrome is Correct:** Gardner’s syndrome is a clinical variant of **Familial Adenomatous Polyposis (FAP)**, caused by a mutation in the **APC gene** on chromosome 5q21. It is characterized by the systemic manifestation of: * **Colonic polyps:** 100% risk of progression to colorectal carcinoma if not treated. * **Extra-colonic bone findings:** Osteomas (most common in the mandible). * **Dental abnormalities:** Impacted supernumerary teeth, odontomas, and congenitally missing teeth. * **Soft tissue tumors:** Epidermoid cysts, fibromas, and desmoid tumors. **2. Why the Other Options are Incorrect:** * **Cleidocranial dysostosis:** While it features supernumerary teeth, it is characterized by clavicular hypoplasia (allowing shoulders to touch) and delayed closure of fontanelles, not osteomas or sebaceous cysts. * **Ectodermal dysplasia:** This typically presents with **hypodontia** (missing teeth) and conical-shaped teeth, along with sparse hair and anhidrosis, which contradicts the "supernumerary teeth" finding. * **Osteogenesis imperfecta:** Characterized by blue sclera, hearing loss, and multiple fractures due to Type I collagen defects. It does not present with osteomas or sebaceous cysts. **High-Yield Clinical Pearls for NEET-PG:** * **CHRPE:** Congenital Hypertrophy of Retinal Pigment Epithelium is often the earliest detectable sign of Gardner’s syndrome. * **Desmoid Tumors:** These are aggressive fibroblastic tumors that often occur post-surgery in Gardner’s patients. * **Screening:** Patients with these extra-intestinal markers must undergo immediate **colonoscopy**, as malignant transformation of polyps occurs by age 40.

Q: Two siblings have osteogenesis imperfecta, but their parents are unaffected. Which of the following genetic mechanisms best explains this inheritance pattern?

Germline mosaicism. ### Explanation **Correct Answer: C. Germline mosaicism** **Mechanism:** Germline (or gonadal) mosaicism occurs when a mutation happens in a precursor germ cell during early embryonic development of a parent [1]. As a result, a proportion of the parent's gametes (sperm or eggs) carry the mutation, while their somatic cells do not. This explains why the **parents are phenotypically normal** (unaffected), yet can have **multiple children** with the same autosomal dominant condition like Osteogenesis Imperfecta (OI) [1]. **Why other options are incorrect:** * **A. Anticipation:** Refers to the increasing severity or earlier onset of a disease in successive generations, typically seen in trinucleotide repeat disorders (e.g., Huntington’s disease, Fragile X). * **B. Genomic imprinting:** Involves differential gene expression depending on whether the allele is inherited from the mother or father (e.g., Prader-Willi and Angelman syndromes) [2]. * **D. New mutation (De novo):** While OI often results from new mutations, a single de novo mutation would typically affect only **one** sibling. The occurrence of the disease in **two** siblings with unaffected parents strongly points toward mosaicism in the parental germline rather than two separate, coincidental new mutations. **NEET-PG High-Yield Pearls:** * **Classic Examples:** Germline mosaicism is a high-yield explanation for **Osteogenesis Imperfecta** and **Duchenne Muscular Dystrophy** when multiple siblings are affected but parents are normal. * **Recurrence Risk:** In cases of germline mosaicism, the recurrence risk for future siblings is higher than the general population (usually 1-5%), despite the parents testing negative for the mutation in blood samples. * **OI Type 2:** This is the most severe (perinatal lethal) form and is frequently associated with this inheritance pattern in board exams.

Q: The Philadelphia chromosome is associated with which genetic event?

Balanced translocation. ### Explanation **1. Why "Balanced Translocation" is Correct:** The Philadelphia chromosome (Ph) is the hallmark of **Chronic Myeloid Leukemia (CML)** [1]. It results from a **reciprocal (balanced) translocation** between chromosomes **9 and 22**, denoted as **t(9;22)(q34;q11)** [1]. * In this process, the *ABL1* proto-oncogene from chromosome 9 moves to the *BCR* (Breakpoint Cluster Region) on chromosome 22 [1]. * This creates a **BCR-ABL1 fusion gene**, which encodes a constitutively active **tyrosine kinase** [1]. This protein drives uncontrolled cellular proliferation and inhibits apoptosis. It is "balanced" because genetic material is exchanged without significant loss or gain of DNA [1]. **2. Why Other Options are Incorrect:** * **Deletion (A):** While deletions occur in many cancers (e.g., 5q- syndrome), the Philadelphia chromosome specifically requires the fusion of two distinct gene segments from different chromosomes. * **Break DNA (B):** DNA breaking is a prerequisite step for any translocation, but it is a generic process, not the defining genetic event of the Philadelphia chromosome [2]. * **Balanced Transcription (D):** This is a distractor term. Transcription is the process of mRNA synthesis; the Philadelphia chromosome is a structural **cytogenetic** abnormality at the DNA level. **3. Clinical Pearls for NEET-PG:** * **Disease Associations:** Found in >95% of CML cases [1]. Also seen in **B-ALL** (indicates poor prognosis) and occasionally in AML. * **Targeted Therapy:** The discovery of this translocation led to the development of **Imatinib (Gleevec)**, a tyrosine kinase inhibitor (TKI) that revolutionized CML treatment [1]. * **Diagnosis:** Identified via **Karyotyping** (shows the shortened chromosome 22), **FISH** (detects the fusion gene), or **RT-PCR** (most sensitive for monitoring minimal residual disease).

Q: A female married to a normal male has a father with vitamin D resistant rickets. What are the chances that her children will be colour blind?

50%. **Explanation:** The core of this question lies in identifying the inheritance patterns of the two conditions mentioned: **Vitamin D Resistant Rickets (VDRR)** and **Color Blindness**. Both are **X-linked** disorders. 1. **Inheritance Pattern:** VDRR is an X-linked Dominant (XLD) condition, while Color Blindness is X-linked Recessive (XLR). 2. **Genotype Determination:** The female’s father has VDRR. Since he is male ($X^D Y$), he must pass his only X chromosome (carrying the disease gene) to all his daughters. Therefore, the female is a **carrier/affected** for VDRR. 3. **The "Trick":** In genetics questions, if two different X-linked traits are discussed in the same lineage without specifying otherwise, they are often linked on the same chromosome. However, the question asks for the probability of **Color Blindness** specifically. 4. **The Calculation:** The female is a carrier for Color Blindness ($X^C X$). She is married to a normal male ($XY$). * **Daughters:** 50% normal ($XX$), 50% carriers ($X^C X$). * **Sons:** 50% normal ($XY$), 50% color blind ($X^C Y$). * **Total Children:** Out of all possible offspring, 50% (the sons) have a 50% chance, and daughters have a 0% chance of phenotype expression. However, in NEET-PG, if the mother is a carrier for an XLR trait, the standard probability for

Question 1

Which of the following is NOT a feature of Marfan's syndrome?

Accepted Answer

Reduced joint mobility

Answer

Arachnodactyly

Answer

Dislocation of the lens

Answer

Mitral regurgitation

Question 2

Which of the following conditions is associated with Turner syndrome?

Accepted Answer

Coarctation of the aorta

Answer

Aortic dissection

Answer

Aortic regurgitation

Answer

Pulmonic stenosis

Question 3

Which of the following statements about congenital adrenal hyperplasia is not true?

Accepted Answer

Hypokalemic alkalosis is seen.

Answer

21-alpha hydroxylase deficiency is the most common cause.

Answer

Males present with precocious puberty.

Answer

Females present with ambiguous genitalia.

Question 4

Which cardiac anomaly is commonly seen in Noonan's syndrome?

Accepted Answer

Pulmonary Stenosis

Answer

Ventricular Septal Defect (VSD)

Answer

Atrial Septal Defect (ASD)

Answer

Coarctation of the Aorta

Question 5

A 22-year-old patient presents with multiple neural tumors, pigmented iris hamartomas, and numerous tan macules on his skin. His father, paternal uncle, and paternal grandfather had a similar condition. What is the most likely diagnosis for this patient?

Accepted Answer

Neurofibromatosis type I

Answer

Ependymoma

Answer

Huntington disease

Answer

Marfan syndrome

Question 6

An 18-year-old patient presents with sebaceous cysts on the scalp and back of the neck, and an osteoma on the right mandible. Radiographs reveal multiple impacted supernumerary teeth in both jaws. These findings suggest which of the following conditions?

Accepted Answer

Gardner's syndrome

Answer

Cleidocranial dysostosis

Answer

Ectodermal dysplasia

Answer

Osteogenesis imperfecta

Question 7

Two siblings have osteogenesis imperfecta, but their parents are unaffected. Which of the following genetic mechanisms best explains this inheritance pattern?

Accepted Answer

Germline mosaicism

Answer

Anticipation

Answer

Genomic imprinting

Answer

New mutation

Question 8

The Philadelphia chromosome is associated with which genetic event?

Accepted Answer

Balanced translocation

Answer

Deletion

Answer

Break DNA

Answer

Balanced transcription

Question 9

Kartagener syndrome is associated with which of the following conditions?

Accepted Answer

Asthenozoospermia

Answer

Oligospermia

Answer

Blockage of the epididymis

Answer

Undescended testes

Question 10

A female married to a normal male has a father with vitamin D resistant rickets. What are the chances that her children will be colour blind?

Accepted Answer

50%

Answer

0%

Answer

75%

Answer

100%

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?