Genetics and Disease Practice Questions

Q: Seminal vesicles and vas deferens would be bilaterally absent congenitally in which of the following conditions?

Cystic fibrosis. ***Cystic fibrosis*** - **Congenital bilateral absence of the vas deferens (CBAVD)** is found in over 95% of males with cystic fibrosis, often leading to infertility. - This condition results from mutations in the **CFTR gene**, which is responsible for chloride transport, causing thick, viscous secretions that block or prevent the development of these structures. *Kartagener syndrome* - This syndrome is a subgroup of **primary ciliary dyskinesia**, characterized by a triad of *situs inversus*, chronic sinusitis, and bronchiectasis. - While it causes **infertility due to immotile sperm**, the male reproductive tract organs like the vas deferens and seminal vesicles are typically present. *Klinefelter syndrome* - Individuals with Klinefelter syndrome have a **47,XXY karyotype** and typically present with small testes, azoospermia, and hypogonadism [1]. - However, the **vas deferens and seminal vesicles are usually present**, though they may be underdeveloped or dysfunctional. *Kallmann syndrome* - This is a form of **hypogonadotropic hypogonadism** associated with anosmia or hyposmia (impaired sense of smell). - It results from a failure of GnRH-producing neurons to migrate to the hypothalamus, affecting hormone production, but the **anatomical structures of the vas deferens and seminal vesicles are usually intact**.

Q: A patient presented with reduced levels of high-density lipoprotein, and ABCA1 mutation. On examination, tonsils appeared as shown in the image. What is the diagnosis?

Tangier disease. ***Tangier disease*** - This condition is characterized by **very low HDL levels** due to mutations in the **ABCA1 gene**, which impairs cholesterol efflux from cells. - The classic physical finding is **enlarged, orange-yellow tonsils** due to cholesterol ester deposition, seen in the provided image. *Fabry disease* - This is an **X-linked lysosomal storage disorder** caused by a deficiency of **alpha-galactosidase A**, leading to globotriaosylceramide accumulation. - Clinical features include **neuropathic pain**, **angiokeratomas**, **corneal opacities**, and early renal and cardiac disease, not orange-yellow tonsils. *Niemann-Pick disease* - This is a group of **autosomal recessive lysosomal storage disorders** caused by deficiencies in enzymes like acid sphingomyelinase or proteins involved in cholesterol processing. - It typically presents with **hepatosplenomegaly**, **neurodegeneration** (especially type A and B), and **lung involvement**, but not oral lesions as depicted. *Gaucher disease* - This is an **autosomal recessive lysosomal storage disease** resulting from a deficiency of the enzyme **beta-glucosidase**, leading to accumulation of glucocerebroside. - Characteristic features include **hepatosplenomegaly**, **bone pain** and crises, and **pancytopenia**, without any specific tonsillar findings.

Q: Which of the following statements are true about familial adenomatous polyposis? 1. It is autosomal recessive 2. If not treated, 100% of the cases progress to adenocarcinoma colon. 3. It is associated with a gene mutation in KRAS 4. It is associated with congenital hypertrophy of the retinal pigment epithelium.

2 and 4. ***2 and 4*** - Without treatment, **familial adenomatous polyposis (FAP)** leads to colorectal **adenocarcinoma** in 100% of cases, due to the accumulation of numerous adenomatous polyps throughout the colon. - FAP is strongly associated with **congenital hypertrophy of the retinal pigment epithelium (CHRPE)**, which can be an early diagnostic marker [1]. *None of the options* - This statement is incorrect because FAP does indeed involve the progression to adenocarcinoma and is associated with CHRPE. - The combination of these two true statements makes this option invalid. *1 and 4* - FAP is inherited in an **autosomal dominant** manner, not autosomal recessive [1]. - While statement 4 (association with CHRPE) is true, statement 1 being false makes this option incorrect. *2 and 3* - Although statement 2 (100% progression to adenocarcinoma) is true, statement 3 is incorrect. - FAP is primarily caused by mutations in the **APC gene**, not the KRAS gene [1]. KRAS is more commonly associated with sporadic colorectal cancer progression rather than FAP.

Q: Which pattern of inheritance of disease is associated with consanguinity?

Autosomal recessive. ***Autosomal recessive*** - Consanguineous relationships increase the likelihood of offspring inheriting **two copies of a rare deleterious recessive allele**, one from each parent [1]. - This occurs because relatives share a greater proportion of their genes, making it more probable that both parents are **heterozygous carriers** for the same recessive disorder. *Autosomal dominant* - In autosomal dominant disorders, only **one copy of the altered gene** is needed to cause the disease, so expression is not typically influenced by consanguinity. - These conditions often manifest in every generation and are not more prevalent with increased shared genetic material. *X-linked recessive* - X-linked recessive disorders primarily affect males, as they only have one X chromosome, and are transmitted by carrier females. - While consanguinity can theoretically increase the carrier rate within a population, its direct impact on the inheritance pattern of an X-linked trait in a single family is less pronounced compared to autosomal recessive conditions. *X-linked dominant* - X-linked dominant disorders are expressed in heterozygous females and hemizygous males, with affected males often having more severe disease. - The inheritance pattern is not significantly influenced by consanguinity, as only one copy of the affected gene on the X chromosome is sufficient for disease manifestation.

Q: Which of the following is an Autosomal Dominant disease?

Von Willebrand disease. ***Von Willebrand disease*** - This is an **autosomal dominant** inherited disorder caused by a deficiency or dysfunction of **von Willebrand factor**, crucial for normal hemostasis [1], [2]. - It often presents with **mucocutaneous bleeding** like nosebleeds, easy bruising, and heavy menstrual bleeding [2]. *Wilson's disease* - This is an **autosomal recessive** disorder characterized by defective copper metabolism and accumulation in various organs, most notably the liver and brain. - Clinical features include **hepatic dysfunction**, neurologic symptoms like **tremors**, and **Kayser-Fleischer rings** in the eyes. *Cystic fibrosis* - This is an **autosomal recessive** disorder caused by mutations in the **CFTR gene**, leading to abnormal chloride transport. - It primarily affects the lungs and digestive system, causing **thick mucus production** and recurrent infections. *Friedreich's ataxia* - This is an **autosomal recessive** neurodegenerative disorder typically caused by a **GAA trinucleotide repeat expansion** in the FXN gene. - Key symptoms include progressive **ataxia**, dysarthria, and often heart problems.

Q: A child presents with abdominal pain, arthralgia, hematuria, and hypertension. What is the diagnosis?

Hemolytic uremic syndrome. ***Hemolytic uremic syndrome*** - The combination of **abdominal pain**, **hematuria**, and **hypertension** in a child, particularly after a diarrheal illness, is highly suggestive of **hemolytic uremic syndrome (HUS)** [1], [2]. - HUS is characterized by **microangiopathic hemolytic anemia**, **thrombocytopenia**, and **acute kidney injury**, which can manifest as hematuria and hypertension [1], [2]. *Dengue* - While **abdominal pain** and **arthralgia** can be symptoms of dengue, it typically also presents with **fever**, **rash**, and **bleeding manifestations** like petechiae or mucosal bleeding. - Dengue does not typically cause **hematuria** with **hypertension** as a primary feature of renal involvement. *Rheumatic fever* - **Rheumatic fever** is characterized by **arthralgia** (migratory arthritis), but it is primarily a sequela of **Streptococcal pharyngitis** and presents with **carditis**, **chorea**, **erythema marginatum**, and **subcutaneous nodules**. - It does not typically cause the combination of **abdominal pain**, **hematuria**, and **hypertension** seen here. *Henoch-Schönlein Purpura* - **Henoch-Schönlein Purpura (HSP)** involves **abdominal pain**, **arthralgia**, and **hematuria**, and can sometimes cause hypertension. - However, the hallmark of HSP is a **palpable purpuric rash** on the lower extremities and buttocks, which is not mentioned in the patient's presentation.

Q: Which of the following provide protection against malaria except

PNH. ***PNH*** - **Paroxysmal nocturnal hemoglobinuria (PNH)** is a rare, acquired clonal disorder of hematopoietic stem cells characterized by complement-mediated hemolysis. - It does not offer any known protective advantage against malaria infection; in fact, chronic hemolysis could potentially complicate malaria diagnosis or management. *Thalassemia* - Individuals with **thalassemia traits (heterozygotes)**, particularly alpha-thalassemia, have red blood cells that are more resistant to malarial parasite invasion and growth [1]. - This protection is thought to arise from altered red cell morphology, reduced parasite multiplication, and enhanced clearance of infected cells. *Sickle cell anemia* - The **heterozygous state (sickle cell trait)** provides significant protection against severe malaria, as the altered hemoglobin S in red blood cells inhibits parasite growth and promotes early clearance of infected cells [1], [2]. - Although the homozygous state (sickle cell anemia) can be severe, even carriers benefit from reduced malaria susceptibility. *Duffy blood group* - Absence of the **Duffy antigen on red blood cells**, common in West African populations, provides complete protection against infection with **Plasmodium vivax** malaria. - The Duffy antigen receptor is essential for *P. vivax* to invade human red blood cells.

Q: A 10-year-old girl presents with severe joint laxity, scoliosis, and a history of easy bruising. Which of the following conditions is most likely?

Ehlers-Danlos syndrome. ***Ehlers-Danlos syndrome*** - This syndrome is characterized by defects in **collagen synthesis** and structure, leading to **joint hypermobility** (laxity) [1], skin hyperextensibility, and fragility, which explains the easy bruising [1]. - **Scoliosis** is a common musculoskeletal manifestation due to weakened connective tissue support [1]. *Marfan's syndrome* - While Marfan's syndrome also presents with **joint laxity** and **scoliosis**, its defining features include distinct skeletal abnormalities (e.g., **arachnodactyly**, sternal deformities) and **cardiovascular abnormalities** (e.g., aortic root dilatation), which are not mentioned here. - **Easy bruising** is not a prominent feature of Marfan's syndrome. *Rheumatoid arthritis* - This is an **autoimmune inflammatory arthritis** primarily affecting synovial joints, causing pain, swelling, and stiffness, often symmetrically. - It does not typically present with severe **joint laxity** throughout the body, **scoliosis**, or **easy bruising** as primary features in a 10-year-old. *Osteogenesis imperfecta* - This condition is characterized by **brittle bones** due to defective collagen, leading to recurrent **fractures** with minimal trauma. - While patients can have some **joint laxity** and **scoliosis**, the most prominent symptom is bone fragility, often accompanied by **blue sclerae**, which is not mentioned, and easy bruising is less indicative than in EDS.

Q: Most common cause of syndromic deafness is:

Waardenburg syndrome. **Waardenburg syndrome** - This is the **most common cause of syndromic deafness**, characterized by hearing loss combined with pigmentary anomalies. - Key features include congenital sensorineural hearing loss, heterochromia iridum (different colored eyes), a white forelock, and premature graying of hair. *Pendred syndrome* - This syndrome is the **second most common cause of syndromic deafness** and is associated with goiter (enlarged thyroid gland). - It results from mutations in the **SLC26A4 gene** and is characterized by sensorineural hearing loss and inner ear malformations (Mondini dysplasia). *Usher syndrome* - This is the **most common cause of combined deafness and blindness**, affecting both hearing and vision. - It involves sensorineural hearing loss and progressive **retinitis pigmentosa**, leading to night blindness and eventual vision loss. *All of the options* - While all listed syndromes cause syndromic deafness, Waardenburg syndrome is specifically identified as the **most common single cause**. - Therefore, choosing "all of the options" would be incorrect as it doesn't pinpoint the *most common* cause.

Q: Submucosal neuroma is associated with

MEN 2B. ***MEN 2B (Multiple Endocrine Neoplasia Type 2B)*** - **Submucosal neuromas** are a distinctive feature of MEN 2B, specifically noticeble as mucosal neuromas on the lips, tongue, and gastrointestinal tract. - This syndrome is characterized by the presence of **medullary thyroid carcinoma**, **pheochromocytoma**, and mucocutaneous neuromas, without hyperparathyroidism. *MEN 2A (Multiple Endocrine Neoplasia Type 2A)* - MEN 2A is characterized by **medullary thyroid carcinoma**, **pheochromocytoma**, and **primary hyperparathyroidism**. - It does not typically feature extensive **submucosal neuromas** as a primary diagnostic criterion. *MEN 1 (Multiple Endocrine Neoplasia Type 1)* - MEN 1 involves tumors of the **parathyroid glands**, **anterior pituitary**, and **pancreatic islet cells** (the '3 Ps'). - **Submucosal neuromas** are not a component of the MEN 1 syndrome. *None of the options* - This option is incorrect because **submucosal neuromas** are a characteristic finding in MEN 2B.

Question 1

Seminal vesicles and vas deferens would be bilaterally absent congenitally in which of the following conditions?

Accepted Answer

Cystic fibrosis

Answer

Kartagener syndrome

Answer

Klinefelter syndrome

Answer

Kallmann syndrome

Question 2

A patient presented with reduced levels of high-density lipoprotein, and ABCA1 mutation. On examination, tonsils appeared as shown in the image. What is the diagnosis?

Accepted Answer

Tangier disease

Answer

Fabry disease

Answer

Niemann-Pick disease

Answer

Gaucher disease

Question 3

Which of the following statements are true about familial adenomatous polyposis?

1. It is autosomal recessive
2. If not treated, 100% of the cases progress to adenocarcinoma colon.
3. It is associated with a gene mutation in KRAS
4. It is associated with congenital hypertrophy of the retinal pigment epithelium.

Accepted Answer

2 and 4

Answer

None of the options

Answer

1 and 4

Answer

2 and 3

Question 4

Which pattern of inheritance of disease is associated with consanguinity?

Accepted Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X linked recessive

Answer

X linked dominant

Question 5

Which of the following is an Autosomal Dominant disease?

Accepted Answer

Von Willebrand disease

Answer

Wilson's disease

Answer

Cystic fibrosis

Answer

Friedreich's ataxia

Question 6

A child presents with abdominal pain, arthralgia, hematuria, and hypertension. What is the diagnosis?

Accepted Answer

Hemolytic uremic syndrome

Answer

Dengue

Answer

Rheumatic fever

Answer

Henoch-Schönlein Purpura

Question 7

Which of the following provide protection against malaria except

Accepted Answer

PNH

Answer

Thalassemia

Answer

Sickle cell anemia

Answer

Duffy blood group

Question 8

A 10-year-old girl presents with severe joint laxity, scoliosis, and a history of easy bruising. Which of the following conditions is most likely?

Accepted Answer

Ehlers-Danlos syndrome

Answer

Marfan's syndrome

Answer

Rheumatoid arthritis

Answer

Osteogenesis imperfecta

Question 9

Most common cause of syndromic deafness is:

Accepted Answer

Waardenburg syndrome

Answer

Pendred syndrome

Answer

Usher syndrome

Answer

All of the options

Question 10

Submucosal neuroma is associated with

Accepted Answer

MEN 2B

Answer

MEN 2 A

Answer

MEN 1

Answer

None of the options

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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