Genetics and Disease Practice Questions

Q: A 40-year-old male presents with recurrent nasal polyps and asthma. Which additional condition should be screened for in this patient?

Samter's triad. The combination of **nasal polyps**, **asthma**, and **aspirin sensitivity (or NSAID-exacerbated respiratory disease)** defines Samter's triad, also known as aspirin-exacerbated respiratory disease (AERD) [1]. This condition involves an abnormal arachidonic acid metabolism leading to increased leukotriene production, which exacerbates respiratory symptoms. The classical aspirin-sensitive patient often presents in middle age with asthma, rhinosinusitis, and nasal polyps [1]. *Cystic fibrosis* - While **nasal polyps** can be a feature of **cystic fibrosis (CF)**, especially in children, the primary concern in adults with recurrent polyps and asthma is less likely to be CF without other typical systemic manifestations (e.g., recurrent lung infections, pancreatic insufficiency). - Confirmation of CF requires sweat chloride testing or genetic analysis for **CFTR mutations**. *Allergic fungal sinusitis* - This condition is characterized by **nasal polyps** and asthma-like symptoms, driven by an allergic reaction to fungal elements in the sinuses. - However, it is a specific diagnosis within rhinosinusitis and doesn't encompass the broad spectrum of respiratory hypersensitivity seen in Samter's triad (especially the aspirin sensitivity component). *Vasomotor rhinitis* - **Vasomotor rhinitis** primarily involves **non-allergic rhinitis** symptoms such as nasal congestion, runny nose, and sneezing, often triggered by irritants or temperature changes. - It typically does not involve **nasal polyps** or is associated with **asthma**, and certainly not with aspirin sensitivity.

Q: 25-year-old man presents for a routine physical examination. The patient is tall and on examination, he was found to have an early diastolic murmur. His family pedigree is given below (image attached). Which of the following is the mode of inheritance by which the disease is likely to be transmitted?

Autosomal Dominant. ***Autosomal Dominant*** - The pedigree shows that the disease appears in every generation, and affected individuals have at least one affected parent (e.g., I-1 passes it to II-1, II-5, II-8). This pattern is characteristic of **dominant inheritance**. - Both males and females are affected, and affected fathers can pass the trait to their sons (e.g., I-1 to II-1), ruling out X-linked inheritance and supporting an **autosomal dominant** mode. *Autosomal Recessive* - In autosomal recessive inheritance, affected individuals typically have **unaffected parents** (who are carriers), and the disease often skips generations. This is not observed in the provided pedigree. - While both males and females can be affected, the presence of affected individuals in every generation and vertical transmission makes recessive inheritance unlikely. *X-Linked Recessive* - X-linked recessive disorders typically show more affected males than females, and affected fathers **cannot pass the trait to their sons**. The pedigree clearly shows affected females and father-to-son transmission (I-1 to II-1 and potentially II-8 to III-6), ruling out this pattern. - Also, all daughters of an affected father would be carriers, and some an affected mother would have affected offspring. *X-Linked Dominant* - In X-linked dominant inheritance, all daughters of an affected father would be affected, and there is no male-to-male transmission. - The pedigree shows instances where affected fathers (like I-1) have unaffected daughters (e.g., II-2, II-4, II-6, II-7), and affected mothers (II-5, II-8) have unaffected children, which contradicts X-linked dominant inheritance.

Q: In Turner's syndrome, which of the following is NOT typically observed?

Mental retardation. ***Mental retardation*** - While there may be some **cognitive difficulties**, severe mental retardation is **not a typical feature** of Turner's syndrome. - Individuals with Turner's syndrome generally have **normal intelligence**, though they may experience challenges in areas like spatial perception. *Short stature* - This is a **classic and almost universal finding** in Turner's syndrome, often one of the first features to be noted [1]. - It results from the **haploinsufficiency of genes** on the X chromosome, particularly the SHOX gene [1]. *Widely spaced nipple* - Often referred to as **shield chest**, this is a characteristic physical finding due to the **broad chest** and increased inter-nipple distance. - This feature, along with other dysmorphic traits, contributes to the distinctive phenotype. *Webbed neck* - A **short, broad neck with redundant skin folds** (webbing) is a common manifestation of Turner's syndrome. - This **lymphatic abnormality** is often present from birth and is a key diagnostic clue.

Q: Gene associated with the development of Peutz-Jeghers syndrome is?

STK11. ***STK11*** - **Peutz-Jeghers syndrome (PJS)** is an autosomal dominant disorder caused by a germline mutation in the **STK11 (serine/threonine kinase 11)** gene. - The STK11 gene acts as a **tumor suppressor**, and its inactivation leads to the characteristic hamartomatous polyps and increased cancer risk seen in PJS [1]. *PTEN* - Mutations in the **PTEN gene** are associated with **Cowden syndrome**, another hereditary polyposis syndrome. - Cowden syndrome is characterized by hamartomatous polyps, mucocutaneous lesions, and an increased risk of breast, thyroid, and endometrial cancers. *KRAS* - The **KRAS gene** is a proto-oncogene frequently mutated in various cancers, including colorectal cancer, but it is not directly associated with the primary genetic defect of Peutz-Jeghers syndrome. - **KRAS mutations** are often found in sporadic colorectal cancers and can influence response to certain therapies. *BRCA 1* - The **BRCA1 gene** is a well-known tumor suppressor gene primarily associated with an increased risk of hereditary breast and ovarian cancers. - It plays a crucial role in DNA repair and is not directly involved in the pathogenesis of Peutz-Jeghers syndrome.

Q: Which of the following is NOT a feature of Abetalipoproteinemia?

Elevated plasma apolipoprotein B levels. Elevated plasma apolipoprotein B levels - **Abetalipoproteinemia** is characterized by the **absence** or extremely **low levels** of apolipoprotein B due to a defect in microsomal triglyceride transfer protein (MTP). - This genetic disorder prevents the assembly and secretion of **chylomicrons**, **VLDL**, and **LDL**, all of which contain apolipoprotein B. *Plasma levels of cholesterol and triglyceride are extremely low* - This is a direct consequence of the inability to form and secrete lipoproteins such as **chylomicrons** (transport dietary triglycerides) and **VLDL/LDL** (transport endogenous lipids and cholesterol). - The lack of these lipoproteins results in **malabsorption of fats** and fat-soluble vitamins, contributing to the low plasma lipid levels. *Manifest in early childhood with diarrhea* - **Fat malabsorption** due to the absence of chylomicrons leads to **steatorrhea** (fatty stools), which is often observed as chronic diarrhea in infancy. - Failure to thrive and abdominal distension are also common early GI symptoms. *Progressive pigmented retinopathy seen* - This is a neurological and ocular manifestation resulting from severe **deficiency of fat-soluble vitamins**, particularly **vitamin A and E** [1]. - **Vitamin A deficiency** contributes to poor vision and **retinopathy**, while **vitamin E deficiency** leads to progressive neurological symptoms like ataxia and peripheral neuropathy [1].

Q: Following genetic counselling in a family for Familial polyposis coli (FPC), what is the next appropriate screening test for at-risk individuals?

Colonoscopy. Colonoscopy - **Colonoscopy** is the gold standard for screening individuals at risk for **Familial Adenomatous Polyposis (FAP)**, also known as Familial Polyposis Coli (FPC), as it allows for visualization of the entire colon and removal of polyps [1]. - Screening typically begins in **early adolescence (10-12 years)** due to the high risk of developing multiple adenomatous polyps and subsequent colorectal cancer [1]. Flexible sigmoidoscopy - While useful for inspecting the lower colon, a **flexible sigmoidoscopy** does not visualize the entire colon, which is essential for FAP given that polyps can occur throughout the large bowel [3]. - It would miss polyps in the **proximal colon**, leading to an inadequate assessment of cancer risk in FAP patients [1]. Occult blood in stools - Testing for **occult blood in stools** is a general screening tool for colorectal cancer but is not sensitive enough for FAP, where the goal is to detect and remove polyps before they become malignant. - A negative result does not rule out the presence of **adenomatous polyps**, which are the hallmark of FAP. APC gene - **APC gene** testing is used for **genetic diagnosis** to identify individuals who carry the FAP mutation, but it is not a screening test for adenomatous polyps or cancer themselves [2]. - Once a family member is identified with the APC gene mutation, subsequent surveillance for polyps requires direct visualization methods like colonoscopy [1].

Q: Which karyotype is commonly associated with true hermaphroditism?

46,XX. ***46,XX*** - While various karyotypes can be associated with **true hermaphroditism**, the majority of cases (approximately 60-70%) present with a **46,XX karyotype** [1]. - This karyotype indicates the presence of **XX chromosomes**, typically associated with females, but in true hermaphroditism, both ovarian and testicular tissue are present [1]. *45,X (Turner syndrome)* - This karyotype is classically associated with **Turner syndrome**, characterized by the absence of one X chromosome [2]. - Individuals with Turner syndrome are typically phenotypically female but experience **gonadal dysgenesis**, leading to streak gonads and infertility, not the presence of both ovarian and testicular tissue [2]. *47,XY,+9* - This karyotype indicates an extra copy of chromosome 9 in an individual who is otherwise karyotypically male (XY). - This is a rare chromosomal abnormality that can lead to a variety of developmental issues and birth defects, but it is **not typically associated with true hermaphroditism**. *47,XXX* - This karyotype is known as **Triple X syndrome** or **Trisomy X**, where an individual has three X chromosomes [3]. - Individuals with Triple X syndrome are phenotypically female and often have mild or no clinical symptoms, though some may experience learning difficulties or fertility issues; it does **not involve the development of both ovarian and testicular tissue** [3].

Q: A 25-year-old man presents for a routine physical examination. He is tall and has an early diastolic murmur on examination. Based on the clinical findings, which of the following is the most likely mode of inheritance for the condition?

AD. ### AD - The combination of **tall stature** and an **early diastolic murmur** is highly suggestive of **Marfan syndrome**, which is inherited in an **autosomal dominant** pattern [1]. - This mode of inheritance means that only one copy of the mutated gene (FBN1) is sufficient to cause the disorder [1]. ### AR - **Autosomal recessive** disorders typically require two copies of a mutated gene for the condition to manifest, and patients are often born to unaffected carriers. - Marfan syndrome does not follow this inheritance pattern [1]. ### XLR - **X-linked recessive** disorders primarily affect males, with females usually being carriers or less severely affected. - While Marfan syndrome can affect both sexes, its inheritance pattern is not linked to the X chromosome. ### XLD - **X-linked dominant** disorders are passed from fathers to all daughters but not to sons, and from mothers to half of their children regardless of sex. - This pattern is not consistent with the genetic transmission of Marfan syndrome.

Question 1

A 40-year-old male presents with recurrent nasal polyps and asthma. Which additional condition should be screened for in this patient?

Accepted Answer

Samter's triad

Answer

Allergic fungal sinusitis

Answer

Vasomotor rhinitis

Answer

Cystic fibrosis

Question 2

25-year-old man presents for a routine physical examination. The patient is tall and on examination, he was found to have an early diastolic murmur. His family pedigree is given below (image attached). Which of the following is the mode of inheritance by which the disease is likely to be transmitted?

Accepted Answer

Autosomal Dominant

Answer

Autosomal Recessive

Answer

X-Linked Recessive

Answer

X-Linked Dominant

Question 3

In Turner's syndrome, which of the following is NOT typically observed?

Accepted Answer

Mental retardation

Answer

Short stature

Answer

Widely spaced nipple

Answer

Webbed neck

Question 4

Which of the following statements about Von Hippel-Lindau (VHL) syndrome is true?

Accepted Answer

Regular screening for clear cell carcinoma of the kidneys is essential.

Answer

It is an autosomal recessive condition.

Answer

Central nervous system involvement is rare.

Answer

The VHL gene acts as a growth promoter.

Question 5

Gene associated with the development of Peutz-Jeghers syndrome is?

Accepted Answer

STK11

Answer

PTEN

Answer

KRAS

Answer

BRCA 1

Question 6

Which of the following is NOT a feature of Abetalipoproteinemia?

Accepted Answer

Elevated plasma apolipoprotein B levels

Answer

Plasma levels of cholesterol and triglyceride are extremely low

Answer

Manifest in early childhood with diarrhea

Answer

Progressive pigmented retinopathy seen

Question 7

Which one of the following statements is correct regarding chronic granulomatous disease (CGD)?

Accepted Answer

Recurrent infections with catalase-positive organisms are common in this disease.

Answer

Nitrobluetetrazolium test is useful for screening

Answer

It is characterized by abnormal bacterial killing.

Answer

It is an X-linked recessive disease.

Question 8

Following genetic counselling in a family for Familial polyposis coli (FPC), what is the next appropriate screening test for at-risk individuals?

Accepted Answer

Colonoscopy

Answer

Flexible sigmoidoscopy

Answer

Occult blood in stools

Answer

APC gene

Question 9

Which karyotype is commonly associated with true hermaphroditism?

Accepted Answer

46,XX

Answer

47,XY,+9

Answer

45,X (Turner syndrome)

Answer

47,XXX

Question 10

A 25-year-old man presents for a routine physical examination. He is tall and has an early diastolic murmur on examination. Based on the clinical findings, which of the following is the most likely mode of inheritance for the condition?

Accepted Answer

AD

Answer

AR

Answer

XLR

Answer

XLD

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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