Genetics and Disease Practice Questions

Q: Which of the following laboratory findings is the MOST characteristic of Wilson's disease?

Increased urinary copper excretion. ***Low ceruloplasmin and high urinary copper*** - In Wilson's disease, there is decreased **ceruloplasmin** due to impaired copper metabolism, leading to low levels in the serum [1]. - The condition results in **increased urinary copper excretion**, which is a hallmark feature and confirms the diagnosis [2]. *Low urinary copper* - Wilson's disease presents with **high urinary copper** levels due to excessive copper being expelled by the kidneys. - **Low urinary copper** would suggest a different condition, such as **Chronic liver disease** or **renal tubular disorders**. *High ceruloplasmin* - Patients with Wilson's disease have **low ceruloplasmin levels** rather than high, indicating ineffective copper transport [1]. - **High ceruloplasmin** levels are typically associated with conditions like **inflammation** or **pregnancy** rather than Wilson's disease. *Low serum copper* - In Wilson's disease, serum copper levels are typically **normal or elevated**, not low. - The primary defect is in the transport of copper, resulting in accumulation in tissues, not a deficiency in serum levels [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 855-856. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 132-133.

Q: Which of the following is NOT an X-linked disease?

Cystic Fibrosis. ***DE*** - This oes not correspond to recognized **X-linked diseases**, making it the correct choice of exception. - X-linked diseases primarily include **Duchenne muscular dystrophy** [1] and **hemophilia**, which are not found in this option. *AB* - This an represent **conditions like hemophilia**, which are clearly X-linked. - Many X-linked diseases affect males more severely due to the single X chromosome. *BC* - Similar to AB, this could allude to X-linked conditions, such as **hemophilia A or B**. - X-linked inheritance patterns result in a higher prevalence in males compared to females. *CA* - May also relate to **X-linked disorders**, including **color blindness** or **Duchenne muscular dystrophy** [1]. - These diseases follow a characteristic pattern of inheritance tied to the X chromosome [1].

Q: Genetic anticipation is characteristic of:

Myotonic dystrophy. ### Myotonic dystrophy - **Genetic anticipation** is a hallmark of myotonic dystrophy, where the disease worsens and appears earlier in successive generations due to expansion of **CTG trinucleotide repeats**. - Symptoms include **myotonia** (delayed muscle relaxation), muscle wasting, cataracts, and cardiac conduction defects. ### Duchenne muscular dystrophy - This is an **X-linked recessive** disorder caused by mutations in the **dystrophin gene**, leading to progressive muscle degeneration [1], [2]. - It does not demonstrate genetic anticipation; the severity and age of onset are generally consistent within affected families. ### Emery-Dreifuss muscular dystrophy - Characterized by a classic triad of **humero-peroneal muscle weakness**, **contractures** (especially of elbows, ankles, and neck), and **cardiac conduction abnormalities**. - It is typically inherited in an X-linked, autosomal dominant, or autosomal recessive manner, but does not involve genetic anticipation. ### Becker muscular dystrophy - A milder form of muscular dystrophy than Duchenne, also caused by mutations in the **dystrophin gene**, but results in a partially functional protein. - While it is a progressive muscle weakness disorder, it does not exhibit the phenomenon of genetic anticipation.

Q: Which one of the following disorders is not X-linked recessive?

Charcot-Marie-Tooth disease. **Charcot-Marie-Tooth disease** - Charcot-Marie-Tooth disease encompasses a group of **hereditary neuropathies** that are most commonly inherited in an **autosomal dominant** pattern, though autosomal recessive and X-linked forms exist, but the dominant form is the most prevalent. - Its diverse genetic basis means it's not exclusively an X-linked recessive disorder. *Lesch-Nyhan syndrome* - This is an **X-linked recessive** disorder caused by a deficiency of the enzyme **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)**. - It is characterized by **hyperuricemia**, neurological dysfunction, and self-mutilating behavior. *Hunter syndrome* - Hunter syndrome (Mucopolysaccharidosis Type II) is an **X-linked recessive** lysosomal storage disorder [1]. - It results from a deficiency of the enzyme **iduronate-2-sulfatase** [1]. *Fragile-X syndrome* - Fragile-X syndrome is an **X-linked disorder** and is the most common inherited cause of intellectual disability. - It is caused by an expansion of a **CGG trinucleotide repeat** in the FMR1 gene.

Q: A middle-aged woman with a history of backache who underwent a Schober test and tested positive, and who also has hyperpigmented nose and ears, is most likely diagnosed with:

Ochronosis. ***Ochronosis*** - **Hyperpigmentation of the nose and ears** (due to homogentisic acid accumulation) along with **backache** and a positive **Schober test** (indicating spinal inflexibility from ochronotic arthropathy) are classic features of ochronosis. - This inherited disorder results from a deficiency of **homogentisic acid oxidase**, leading to the accumulation of homogentisic acid. *Ankylosing spondylitis* - While **backache** and a positive **Schober test** (indicating axial skeleton involvement) are characteristic of ankylosing spondylitis, it does not typically present with **hyperpigmented nose and ears**. - **HLA-B27 positivity** and inflammatory back pain improving with activity are key differentiating features not mentioned. *Degenerative disc disease* - This condition is characterized by **chronic backache** due to age-related changes in the intervertebral discs but does not cause **hyperpigmentation of the nose and ears**. - A **positive Schober test** is less specific for degenerative disc disease and is more indicative of widespread spinal stiffness. *Fluorosis* - While severe fluorosis can lead to **skeletal changes** and pain mimicking arthritis, it is primarily associated with **dental mottling** and does not cause characteristic hyperpigmentation of the nose and ears. - มัน usually results from excessive fluoride intake, often from contaminated drinking water.

Q: Which disorder is associated with NARP syndrome, characterized by neuropathy, ataxia, and retinitis pigmentosa?

Mitochondrial function disorder. ***Mitochondrial function disorder*** - NARP syndrome (Neurogenic weakness, Ataxia, Retinitis Pigmentosa) is caused by a specific point mutation in the **MT-ATP6 gene**, which encodes a subunit of the mitochondrial ATP synthase [1]. - This mutation leads to impaired mitochondrial energy production, affecting tissues with high energy demands, such as the **nervous system** and retina [1]. *Glycogen storage disorder* - These disorders involve defects in enzymes responsible for **glycogen synthesis or degradation**, leading to abnormal glycogen accumulation in tissues [1]. - While they can cause muscle weakness and neurological symptoms, the specific constellation of **neuropathy, ataxia, and retinitis pigmentosa** is not characteristic of glycogenoses. *Lysosomal storage disorder* - These conditions result from deficiencies in lysosomal enzymes, causing the accumulation of **undigested macromolecules** within lysosomes. - Symptoms vary widely but typically involve progressive neurological degeneration, organomegaly, and skeletal abnormalities, without the classic NARP presentation. *Lipid storage disorder* - These disorders are characterized by the accumulation of **specific lipids** due to enzyme deficiencies involved in lipid metabolism. - Examples include Gaucher disease and Niemann-Pick disease, which involve different clinical manifestations such as hepatosplenomegaly, bone crises, and various neurological issues, distinct from NARP syndrome.

Q: Which of the following is not a major criterion for diagnosing Marfan syndrome?

Striae over the buttocks. Striae over the buttocks - While striae (stretch marks) can be common in individuals with Marfan syndrome due to connective tissue fragility, they are considered a minor criterion rather than a major one based on the Ghent nosology. - Major criteria are defined by their higher diagnostic specificity and clinical significance in identifying Marfan syndrome. Ectopia lentis - Ectopia lentis (dislocation of the ocular lens) is a major diagnostic criterion for Marfan syndrome and is highly specific to the condition. - It results from the weakness of the suspensory ligaments of the lens due to fibrillin-1 deficiency. Dilatation of the ascending aorta - Aortic root dilatation and aortic dissection are critical cardiovascular manifestations and major diagnostic criteria for Marfan syndrome [1]. - These reflect the systemic connective tissue defect affecting the integrity of the aortic wall and are associated with significant morbidity and mortality [1]. Dural ectasia - Dural ectasia, which is the widening of the dural sac due to weakening of connective tissue, is a major criterion for the diagnosis of Marfan syndrome when observed on imaging studies. - It often occurs in the lumbosacral region and can cause neurological symptoms.

Q: Which of the following is a feature of Ehlers-Danlos syndrome?

Joint hypermobility. ***Pectus excavatum*** - This condition is characterized by a **depression of the sternum**, leading to a sunken chest appearance, and is least commonly associated with Ehlers-Danlos syndrome (EDS). - Other forms of EDS may present with more notable **joint hypermobility** and skin elasticity issues, rather than pectus excavatum [1]. *Kyphoscoliosis* - This is a common complication in certain types of Ehlers-Danlos syndrome, particularly affecting the spine's curvature [1]. - It is associated with **joint hypermobility** and can lead to significant postural abnormalities [1]. *Achalasia* - While achalasia can occur in EDS, it is not a typical or common association. - This esophageal motility disorder primarily affects **swallowing** due to a failure of the lower esophageal sphincter to relax. *Dermatosparaxis* - This form of EDS specifically features **skin fragility** and tearing with minimal trauma, indicating a significant association with the syndrome [1]. - It is characterized by **excessively fragile skin** and is directly linked to the pathogenic mechanisms of EDS [1].

Q: What is the most characteristic finding in familial adenomatous polyposis (FAP)?

Autosomal dominant inheritance. ***Familial adenomatous polyposis affects both males and females equally.*** - Familial adenomatous polyposis (FAP) follows an **autosomal dominant inheritance pattern**, therefore affecting both genders. - It typically presents with **hundreds to thousands of adenomatous polyps** in the colon, leading to a significant risk for colon cancer if untreated [1]. *If not treated, it progresses to malignancy in nearly all cases.* - While untreated FAP has a high risk for colorectal cancer, it does not mean **all cases** progress to malignancy; some may be managed effectively. - Regular screening and prophylactic surgery can significantly **reduce** the malignant potential associated with the condition [1]. *Males and females are affected equally.* - While FAP affects males and females, the tendency for development of certain cancers may vary; stating it affects them **equally** could be misleading due to varying cancer risks. - The inheritance and clinical implications do not make a distinction based on gender despite equal prevalence. *Autosomal dominant inheritance.* - This statement about inheritance is indeed **true**, but it is not the correct statement regarding FAP's equality in affecting genders. - The **mutated APC gene** is responsible for FAP, leading to the widespread formation of polyps and the risk of colon cancer [1].

Question 1

Which of the following statements about Wilson's disease is false?

Accepted Answer

Urinary copper excretion < 100 micrograms/day

Answer

Autosomal recessive

Answer

Serum ceruloplasmin level < 20 mg/dl

Answer

Zinc acetate is used as maintenance therapy

Question 2

Which of the following laboratory findings is the MOST characteristic of Wilson's disease?

Accepted Answer

Increased urinary copper excretion

Answer

Elevated serum copper

Answer

Low serum copper

Answer

Low ceruloplasmin

Question 3

Which of the following is NOT an X-linked disease?

Accepted Answer

Cystic Fibrosis

Answer

Hemophilia A

Answer

Duchenne Muscular Dystrophy

Answer

Color Blindness

Question 4

Genetic anticipation is characteristic of:

Accepted Answer

Myotonic dystrophy

Answer

Duchenne muscular dystrophy

Answer

Emery-Dreifuss muscular dystrophy

Answer

Beckers muscular dystrophy

Question 5

Which one of the following disorders is not X-linked recessive?

Accepted Answer

Charcot-Marie-Tooth disease

Answer

Lesch-Nyhan syndrome

Answer

Hunter syndrome

Answer

Fragile-X syndrome

Question 6

A middle-aged woman with a history of backache who underwent a Schober test and tested positive, and who also has hyperpigmented nose and ears, is most likely diagnosed with:

Accepted Answer

Ochronosis

Answer

Ankylosing spondylitis

Answer

Degenerative disc disease

Answer

Fluorosis

Question 7

Which disorder is associated with NARP syndrome, characterized by neuropathy, ataxia, and retinitis pigmentosa?

Accepted Answer

Mitochondrial function disorder

Answer

Glycogen storage disorder

Answer

Lysosomal storage disorder

Answer

Lipid storage disorder

Question 8

Which of the following is not a major criterion for diagnosing Marfan syndrome?

Accepted Answer

Striae over the buttocks

Answer

Dilatation of the ascending aorta

Answer

Dural ectasia

Answer

Ectopia lentis

Question 9

Which of the following is a feature of Ehlers-Danlos syndrome?

Accepted Answer

Joint hypermobility

Answer

Achalasia

Answer

Kyphoscoliosis

Answer

Dermatosparaxis

Question 10

What is the most characteristic finding in familial adenomatous polyposis (FAP)?

Accepted Answer

Autosomal dominant inheritance

Answer

Predominantly affects males

Answer

If not treated, FAP has a very high risk of progressing to malignancy.

Answer

Males and females are affected equally

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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