Single Gene Disorders — MCQs
What is the interpretation of the given pedigree chart?
Which disease will show the mode of inheritance depicted in this pedigree?
What is the inheritance pattern of Crouzon syndrome?
In which of the following inheritance patterns is father-to-son transmission not observed?
Which of the following is a single gene autosomal recessive disease?
A 3-year-old boy presents with developmental delays and an inability to walk. The fundoscopy image is given below. What is the most likely diagnosis?
Which one of the following is an autosomal dominant disorder?
Wilson's disease has which of the following inheritance?
Which of the following is not an autosomal recessive disorder?
Which one of the following is an autosomal recessive disorder?
Single Gene Disorders Indian Medical PG Practice Questions and MCQs
Question 1: What is the interpretation of the given pedigree chart?
- A. Autosomal dominant (Correct Answer)
- B. Incomplete penetrance
- C. Autosomal recessive
- D. X-linked dominant
Explanation: ***Autosomal dominant*** - The trait appears in **every generation**, indicated by affected individuals in the first, second, and third generations [1]. - Both males and females are affected relatively equally, and affected individuals transmit the trait to approximately half of their offspring, consistent with **vertical transmission** [1]. - **Male-to-male transmission** is present, which definitively rules out X-linked inheritance patterns [1]. *Incomplete penetrance* - This pattern would typically show some individuals who carry the disease-causing genotype but **do not express the phenotype** (unaffected). - In this pedigree, all individuals who are expected to express the trait based on the clear dominant pattern are indeed affected. *Autosomal recessive* - This mode of inheritance would typically show **skipped generations**, meaning affected individuals would often have unaffected parents who are carriers [1]. - In this chart, every affected individual has at least one affected parent, ruling out an autosomal recessive pattern [1]. X-linked dominant - In X-linked dominant inheritance, **no male-to-male transmission** would be observed, as fathers pass their X chromosome only to daughters. - The presence of affected males transmitting the trait to male offspring rules out this inheritance pattern. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 148-151.
Question 2: Which disease will show the mode of inheritance depicted in this pedigree?
- A. Achondroplasia (Correct Answer)
- B. Prader-Willi syndrome
- C. Wilson disease
- D. Wiskott-Aldrich syndrome
- E. Hemophilia A
Explanation: ***Achondroplasia*** - This pedigree shows an **autosomal dominant** inheritance pattern, characterized by affected individuals in every generation, affected offspring with at least one affected parent, and direct transmission from father to son (which **rules out X-linked**). Achondroplasia is an autosomal dominant disorder. - The presence of **affected individuals (shaded squares/circles)** in each successive generation and the 1:1 ratio of affected to unaffected offspring from affected parents mating with unaffected individuals supports autosomal dominant inheritance. *Prader-Willi syndrome* - This syndrome is caused by **genomic imprinting** or a chromosomal deletion on chromosome 15, typically inherited from the father. It does not follow a simple Mendelian dominant or recessive inheritance pattern. - While it has a genetic basis, its inheritance pattern is **complex** and involves specific parental origin of the genetic defect, unlike the clear autosomal dominant pattern shown. *Wilson disease* - Wilson disease is an **autosomal recessive** disorder, meaning affected individuals inherit two copies of the mutated gene (one from each parent). - This pedigree does not show skipped generations or unaffected parents having affected offspring, which would be characteristic of **autosomal recessive** inheritance. *Wiskott-Aldrich syndrome* - Wiskott-Aldrich syndrome is an **X-linked recessive** disorder. This means it primarily affects males, and affected fathers cannot pass the trait to their sons. - The pedigree shows **affected females** (shaded circles) and **father-to-son transmission** (e.g., father in second generation to son in third generation, assuming the leftmost branch is the paternal line), which rules out X-linked inheritance. *Hemophilia A* - Hemophilia A is an **X-linked recessive** disorder affecting the Factor VIII gene, predominantly affecting males. - Similar to Wiskott-Aldrich syndrome, the presence of **father-to-son transmission** in the pedigree rules out X-linked inheritance patterns, as affected fathers cannot pass X-linked traits to their sons.
Question 3: What is the inheritance pattern of Crouzon syndrome?
- A. Autosomal recessive
- B. X-linked recessive
- C. Mitochondrial
- D. Autosomal dominant (Correct Answer)
- E. X-linked dominant
Explanation: ***Autosomal dominant*** - Crouzon syndrome is caused by a mutation in the **FGFR2 gene**, which is inherited in an **autosomal dominant pattern**. - This means only one copy of the mutated gene is needed for an individual to be affected, and there is a 50% chance of passing it to offspring. *Autosomal recessive* - Autosomal recessive conditions require **two copies of the mutated gene** (one from each parent) for the disease to manifest. - While some craniosynostosis syndromes are autosomal recessive, Crouzon syndrome is not. *X-linked recessive* - **X-linked recessive disorders** primarily affect males, as they only have one X chromosome. - Crouzon syndrome affects both males and females equally, ruling out X-linked inheritance. *X-linked dominant* - **X-linked dominant disorders** affect both males and females but often show more severe manifestations in males. - Crouzon syndrome does not follow an X-linked pattern and is not associated with the X chromosome. *Mitochondrial* - **Mitochondrial inheritance** involves genes within the mitochondrial DNA, passed exclusively from the mother to all her children. - This pattern of inheritance does not match the observed transmission of Crouzon syndrome.
Question 4: In which of the following inheritance patterns is father-to-son transmission not observed?
- A. Autosomal dominant inheritance
- B. Autosomal recessive inheritance
- C. Multifactorial inheritance
- D. X-linked recessive inheritance (Correct Answer)
Explanation: ***X-linked recessive inheritance*** - In X-linked inheritance, females have two X chromosomes (XX) and males have one X and one Y chromosome (XY). A father always passes his **Y chromosome** to his son. - He passes his **X chromosome only to his daughters**. Therefore, a father cannot pass an X-linked trait directly to his son. *Autosomal dominant inheritance* - In autosomal dominant inheritance, a disease allele is located on a **non-sex chromosome (autosome)**. - Both males and females can be affected, and **father-to-son transmission is possible** if the father carries the dominant allele on an autosome. *Autosomal recessive inheritance* - This inheritance pattern also involves genes on **autosomes**. - A father can transmit a recessive allele to his son, though the son would only express the trait if he also inherits a recessive allele from his mother. **Father-to-son transmission of the allele is possible**. *Multifactorial inheritance* - This pattern involves the interaction of **multiple genes** and **environmental factors**. - As some of these genes are on autosomes, and environmental factors are independent of sex chromosomes, **father-to-son transmission is observed** for the genetic components.
Question 5: Which of the following is a single gene autosomal recessive disease?
- A. Wilson's disease (Correct Answer)
- B. Tuberous sclerosis
- C. Huntington's disease
- D. Schizophrenia
Explanation: ***Wilson's disease*** - This is an **autosomal recessive disorder** [1] characterized by excessive **copper accumulation** in the liver, brain, and other organs due to a mutation in the ATP7B gene. - Manifestations include **hepatic dysfunction**, neurological symptoms, and characteristic **Kayser-Fleischer rings** in the eyes [1]. *Tuberous sclerosis* - This is an **autosomal dominant disorder** caused by mutations in the TSC1 or TSC2 genes, leading to the formation of benign tumors in multiple organs. - Clinical features include **epilepsy**, intellectual disability, facial angiofibromas, and renal angiomyolipomas. *Huntington's disease* - This is an **autosomal dominant neurodegenerative disorder** caused by a CAG trinucleotide repeat expansion in the HTT gene. - It presents with **progressive chorea**, psychiatric symptoms, and cognitive decline, typically in mid-adulthood. *Schizophrenia* - This is a **complex psychiatric disorder** with a multifactorial etiology, involving a combination of genetic predisposition and environmental factors. - It is not a single gene disorder but rather involves many genes contributing to risk, indicating a **polygenic inheritance pattern**.
Question 6: A 3-year-old boy presents with developmental delays and an inability to walk. The fundoscopy image is given below. What is the most likely diagnosis?
- A. Tay-Sachs disease (Correct Answer)
- B. Hunter syndrome
- C. Hurler syndrome
- D. Gaucher disease
- E. Niemann-Pick disease
Explanation: ***Tay-Sachs disease*** - The image shows a **cherry-red spot** in the macula, a classic ocular finding in Tay-Sachs disease caused by **ganglioside accumulation** in retinal ganglion cells. - The clinical presentation of **developmental delays** and inability to walk in a 3-year-old boy is consistent with the neurodegenerative course of Tay-Sachs disease. - Tay-Sachs is **more common** than Niemann-Pick disease and classically presents with this triad: cherry-red spot, developmental regression, and hypotonia. *Niemann-Pick disease* - Niemann-Pick disease (especially Type A) can also present with a **cherry-red spot** and developmental delay, making it a close differential. - However, Niemann-Pick typically presents earlier (infancy) with more prominent **hepatosplenomegaly** and **sphingomyelin accumulation**, which are not mentioned in this case. - The age of presentation (3 years) and classic fundoscopic finding favor Tay-Sachs over Niemann-Pick. *Hunter syndrome* - Hunter syndrome is a lysosomal storage disorder characterized by **coarse facial features**, hepatosplenomegaly, and skeletal abnormalities, but typically **does not present with a cherry-red spot**. - While developmental delay can occur, the absence of a cherry-red spot and presence of other physical stigmata differentiate it from Tay-Sachs. *Hurler syndrome* - Hurler syndrome is another mucopolysaccharidosis with features similar to Hunter syndrome, including **skeletal deformities**, coarse facial features, and **corneal clouding**, but **not a cherry-red spot**. - The significant developmental regression and the specific fundoscopic finding point away from Hurler syndrome. *Gaucher disease* - Gaucher disease is characterized by **hepatosplenomegaly**, bone pain, and neurologic involvement in some forms, but it is **not typically associated with a cherry-red spot** in the fundus. - While developmental delay can be present, the absence of the pathognomonic ocular finding makes Tay-Sachs a more likely diagnosis.
Question 7: Which one of the following is an autosomal dominant disorder?
- A. Cystic fibrosis
- B. Hereditary spherocytosis (Correct Answer)
- C. Sickle cell anemia
- D. G-6PD deficiency
Explanation: ***Hereditary spherocytosis*** - It is characterized by **autosomal dominant inheritance** [1], leading to the destruction of red blood cells. - Mutations in proteins that maintain the **red blood cell membrane** integrity result in spherocyte formation [1]. *Cystic fibrosis* - This condition follows a **autosomal recessive inheritance pattern**, requiring two copies of the mutated gene for disease manifestation. - It is caused by mutations in the **CFTR gene**, affecting chloride transport and leading to thick secretions. *G-6PD deficiency* - This disorder is inherited in an **X-linked recessive manner** [2], primarily affecting males and transmitted through carrier females. - Characterized by **hemolytic anemia** triggered by certain medications or infections, it does not follow dominant inheritance [2]. *Sickle cell anemia* - Sickle cell anemia is also an **autosomal recessive disorder** [3], meaning affected individuals must inherit two copies of the sickle cell gene. - It results in a mutation in the **HBB gene**, leading to the production of abnormal hemoglobin (HbS) [3].
Question 8: Wilson's disease has which of the following inheritance?
- A. It is an acquired disease
- B. Autosomal recessive (Correct Answer)
- C. X-linked recessive
- D. Autosomal dominant
Explanation: ***Autosomal recessive*** - Wilson's disease is caused by mutations in the **ATP7B gene**, which codes for a copper-transporting ATPase. - For an individual to develop the disease, they must inherit **two copies of the mutated gene**, one from each parent. *It is an acquired disease* - Wilson's disease is a **genetic disorder**, meaning it is inherited, not acquired through environmental factors or lifestyle [1]. - While symptoms may manifest later in life, the underlying cause is a **predisposing genetic mutation** [1]. *X-linked recessive* - X-linked recessive disorders primarily affect males as they have only one X chromosome; however, Wilson's disease **affects both sexes equally**. - The gene responsible for Wilson's disease, **ATP7B**, is located on **chromosome 13**, an autosome, not on the X chromosome. *Autosomal dominant* - In autosomal dominant inheritance, only **one copy of the mutated gene** is sufficient to cause the disease, and it is usually seen in every generation. - Wilson's disease requires **two mutated copies** of the gene to manifest, and carriers (heterozygotes) are typically asymptomatic.
Question 9: Which of the following is not an autosomal recessive disorder?
- A. Sickle cell anaemia
- B. Albinism
- C. Hirschsprung disease (Correct Answer)
- D. Retinoblastoma
Explanation: ***Retinoblastoma*** - Retinoblastoma is caused by mutations in the **RB1 gene** and is inherited in an **autosomal dominant** pattern [1], not recessive. - It typically presents as a **tumor in the retina** of children, which is distinct from the conditions listed. *Albinism* - Albinism is a **genetic condition** characterized by a lack of melanin, inherited in an **autosomal recessive** manner. - It commonly presents with **hypopigmentation** of skin and eyes along with vision problems. *Hirschsprung disease* - Hirschsprung disease involves the **absence of ganglion cells** in the intestine, inherited in an **autosomal recessive** fashion. - It leads to **severe constipation** or intestinal obstruction and is linked to **Neural Crest Cell** development. *Sickle cell anaemia* - Sickle cell anaemia is a **hemoglobin disorder** resulting from a mutation in the HBB gene, inherited as an **autosomal recessive** trait. - Patients typically experience **painful crises** due to the sickling of red blood cells and their blockage of blood flow.
Question 10: Which one of the following is an autosomal recessive disorder?
- A. Cystic fibrosis (Correct Answer)
- B. Huntington's disease
- C. Marfan syndrome
- D. Neurofibromatosis type 1
Explanation: ***Cystic fibrosis*** - **Cystic fibrosis** is caused by mutations in the **CFTR gene**, leading to defective **chloride channel** function. - It is an **autosomal recessive disorder**, meaning an individual must inherit two copies of the mutated gene (one from each parent) to be affected. *Huntington's disease* - **Huntington's disease** is an **autosomal dominant disorder** caused by a mutation in the HTT gene. - Only one copy of the mutated gene is sufficient to cause the disease, resulting in progressive neurodegeneration. *Marfan syndrome* - **Marfan syndrome** is an **autosomal dominant disorder** affecting connective tissue, caused by mutations in the FBN1 gene. - It results in skeletal, ocular, and cardiovascular abnormalities due to defective **fibrillin-1**. *Neurofibromatosis type 1* - **Neurofibromatosis type 1** is an **autosomal dominant disorder** caused by mutations in the NF1 gene. - It is characterized by multiple neurofibromas, café-au-lait macules, and Lisch nodules.
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