Genetics and Disease — MCQs

A 25-year-old woman with amenorrhea has never had menarche. On physical examination, she is 145 cm (4 ft 9 in) tall. She has a webbed neck, a broad chest, and widely spaced nipples. Strong pulses are palpable in the upper extremities, but there are only weak pulses in the lower extremities. On abdominal MR imaging, her ovaries are small, elongated, and tubular. Which of the following karyotypes is she most likely to have?

Q236

Select the FALSE combination of chromosomal pattern and the syndrome:

Q237

Which of the following is a sex linked inherited disease?

Q238

Which is wrong about Crigler-Najjar syndrome Type-1?

Q239

A 22-year-old man complains about his inability to conceive a child. On physical examination, the patient is noted to be tall (6 ft, 5 in) and exhibits gynecomastia and testicular atrophy. Laboratory studies demonstrate increased serum levels of follicle-stimulating hormone. Cytogenetic studies reveal a chromosomal abnormality. What is the most common cause of this patient's chromosomal abnormality?

Q240

Chloride receptor defect is responsible for:

Genetics and Disease Indian Medical PG Practice Questions and MCQs

Question 231: Syndrome which is characterized by 2X chromosomes and 1Y chromosome is:

A. Turner syndrome
B. Marfan syndrome
C. Down syndrome
D. Klinefelter syndrome (Correct Answer)

Explanation: ***Klinefelter syndrome*** - This syndrome is characterized by a **47, XXY karyotype**, meaning individuals have **two X chromosomes** and one Y chromosome [1]. - It affects males, leading to features such as **small testes**, **infertility**, gynecomastia, and often taller stature [1], [3]. *Turner syndrome* - This syndrome is characterized by a **45, X karyotype**, meaning individuals have only **one X chromosome** and no second sex chromosome [2]. - It affects females, leading to features like **short stature**, a **webbed neck**, and ovarian dysgenesis [2]. *Marfan syndrome* - This is an **autosomal dominant genetic disorder** affecting connective tissue, caused by mutations in the **FBN1 gene**. - It is characterized by **tall stature**, long limbs (arachnodactyly), **cardiovascular abnormalities** (e.g., aortic dissection), and ocular problems (e.g., lens dislocation). *Down syndrome* - This syndrome is caused by **trisomy 21**, meaning individuals have an **extra copy of chromosome 21**. - It is characterized by specific **facial features**, intellectual disability, and an increased risk of certain medical conditions like congenital heart defects.

Question 232: Malaria protection comes from all Except

A. Sickle cell anemia
B. Thalassemia
C. G6PD deficiency
D. Acanthocytosis (Correct Answer)

Explanation: ***Acanthocytosis*** - **Acanthocytosis** is characterized by abnormal, spiky red blood cells due to lipid membrane defects and does **not** provide protection against malaria. - While red blood cell abnormalities can sometimes offer malaria resistance, acanthocytosis is not one of these known protective conditions. *Sickle cell anemia* - Individuals with **sickle cell trait (heterozygous)** have red blood cells that are less hospitable to the *Plasmodium falciparum* parasite, providing **significant protection** against severe malaria [2]. - The abnormal hemoglobin in sickle cells can lead to premature destruction of infected red blood cells or inhibit parasite growth. *Thalassemia* - **Thalassemia syndromes**, particularly alpha and beta thalassemia traits, provide a degree of protection against malaria [2]. - The affected red blood cells are less suitable for parasite multiplication, and immune responses may be modulated. *G6PD deficiency* - Individuals with **G6PD deficiency** have red blood cells that are more susceptible to oxidative stress, which can inhibit the growth of malaria parasites [1]. - This deficiency causes premature destruction of infected red blood cells, thereby limiting parasite load and providing **some protection** against severe malaria [1].

Question 233: Hirschsprung disease has association with which of the following conditions?

A. MEN 2B (Correct Answer)
B. Von Hippel Lindau
C. MEN 2A
D. MEN I

Explanation: ***MEN 2B*** - **Hirschsprung disease** is associated with **Multiple Endocrine Neoplasia type 2B (MEN 2B)** due to mutations in the **RET proto-oncogene** [1]. - These patients often present with **pheochromocytoma**, **medullary thyroid carcinoma**, and characteristic **mucosal neuromas** and a **marfanoid habitus**. *Von Hippel-Lindau* - This syndrome is associated with the development of **hemangioblastomas**, **pheochromocytomas**, and **renal cell carcinoma**. - It is caused by mutations in the **VHL tumor suppressor gene** and does not have a direct association with Hirschsprung disease. *MEN 2A* - **MEN 2A** is characterized by **medullary thyroid carcinoma**, **pheochromocytoma**, and **primary hyperparathyroidism**. - While also caused by **RET proto-oncogene** mutations, it typically does not present with Hirschsprung disease [1]. *MEN 1* - **Multiple Endocrine Neoplasia type 1 (MEN 1)** is associated with **tumors of the parathyroid, pituitary, and pancreas** ("3 Ps"). - This syndrome is due to mutations in the **MEN1 tumor suppressor gene** and has no known association with Hirschsprung disease.

Question 234: The commonest mode of inheritance of congenital heart disease is

A. Autosomal recessive
B. Multifactorial (Correct Answer)
C. Sex-linked dominant
D. Autosomal dominant

Explanation: ***Multifactorial*** - **Congenital heart disease (CHD)** is primarily caused by a combination of genetic predispositions and environmental factors [1]. - This **multifactorial inheritance** means that while genes play a role in susceptibility, specific environmental triggers during fetal development are also crucial [1], [4]. *Autosomal recessive* - This mode of inheritance is associated with conditions that only manifest if an individual inherits two copies of a **mutated gene**, one from each parent. - While some rare forms of CHD can be autosomal recessive, it is not the most common inheritance pattern for the majority of cases. *Sex-linked dominant* - **Sex-linked dominant** disorders are caused by mutations on the X chromosome and affect males and females differently, with affected fathers passing the trait to all their daughters but no sons. - This pattern is not typically observed as the primary mode of inheritance for general CHD. *Autosomal dominant* - In **autosomal dominant inheritance**, only one copy of an altered gene is needed for the condition to manifest [2]. - While certain syndromes associated with CHD can be autosomal dominant (e.g., Marfan syndrome), it is not the most frequent mode of inheritance for isolated CHD [3].

Question 235: A 25-year-old woman with amenorrhea has never had menarche. On physical examination, she is 145 cm (4 ft 9 in) tall. She has a webbed neck, a broad chest, and widely spaced nipples. Strong pulses are palpable in the upper extremities, but there are only weak pulses in the lower extremities. On abdominal MR imaging, her ovaries are small, elongated, and tubular. Which of the following karyotypes is she most likely to have?

A. 47, XXX
B. 47, XXY
C. 45, X/46, XX (Correct Answer)
D. 46, X, X (fra)

Explanation: ***45, X/46, XX*** - The mosaic karyotype **45, X/46, XX** is a common variant of **Turner syndrome** [1]. This explains the patient's features like **short stature** [3], **webbed neck**, **broad chest**, **widely spaced nipples**, **streak gonads** (small, elongated, tubular ovaries leading to primary amenorrhea) [2], and **coarctation of the aorta** (strong upper extremity pulses, weak lower extremity pulses) [2]. - **Turner syndrome** is characterized by the absence of all or part of one of the X chromosomes, either outright (45, X) [3] or in a mosaic pattern (45, X/46, XX), leading to ovarian dysgenesis and somatic abnormalities [2]. *47, XXX* - A **47, XXX** karyotype, also known as **Triple X syndrome**, typically presents with phenotypically normal females, although tall stature, learning disabilities, and speech delays can occur [1]. - It does not cause the characteristic physical stigmata of Turner syndrome such as short stature, webbed neck, or cardiovascular defects, nor does it typically lead to streak gonads with primary amenorrhea. *47, XXY* - A **47, XXY** karyotype is characteristic of **Klinefelter syndrome**, which affects males [1], [3]. - Individuals with Klinefelter syndrome present with features such as tall stature, small testes, gynecomastia, and infertility, which are inconsistent with the patient's female gender and reported symptoms. *46, X, X (fra)* - A **46, X, X (fra)** karyotype refers to a normal female karyotype with a **fragile site** on an X chromosome. This is not a recognized cause of the constellation of symptoms described, which are classic for Turner syndrome. - While fragile sites can be associated with certain genetic conditions, they do not explain the specific physical and cardiovascular abnormalities or ovarian dysgenesis seen in this patient.

Question 236: Select the FALSE combination of chromosomal pattern and the syndrome:

A. Swyer's syndrome-46XY
B. Klinefelter's syndrome-47XXY
C. Turner's syndrome-45XO
D. Mayer Rokitansky-46XY (Correct Answer)

Explanation: ***Mayer Rokitansky-46XY*** - Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by **vaginal agenesis** and **uterine anomalies** in individuals with a normal **46,XX** **karyotype**, making 46,XY an incorrect chromosomal pattern for this syndrome. - Individuals with MRKH have female external genitalia and normal ovarian function, differentiating it from disorders of sexual development involving sex chromosome abnormalities. *Swyer's syndrome-46XY* - This is a **correct** combination; Swyer's syndrome is a form of **XY gonadal dysgenesis** where individuals have a **46,XY karyotype** but develop female external genitalia due a non-functional SRY gene [2]. - These individuals typically present with **primary amenorrhea** and **streak gonads**, requiring hormone replacement therapy and gonadectomy to prevent gonadoblastoma. *Klinefelter's syndrome-47XXY* - This is a **correct** combination; Klinefelter's syndrome is characterized by the presence of an **extra X chromosome** in biological males, resulting in a **47,XXY karyotype** [2]. - Affected individuals typically exhibit **hypogonadism**, **infertility**, **gynecomastia**, and often have a taller stature [3]. *Turner's syndrome-45XO* - This is a **correct** combination; Turner's syndrome is characterized by the **absence or partial absence of one X chromosome** in females, resulting in a **45,XO karyotype** [1]. - Clinical features include **short stature**, **ovarian dysgenesis** (streak gonads), **primary amenorrhea**, and distinctive physical features such as a **webbed neck** and **broad chest** [1].

Question 237: Which of the following is a sex linked inherited disease?

A. Hypogamma globuinemia
B. Diamond blackfan disease
C. Down syndrome
D. G6 PD deficiency (Correct Answer)

Explanation: ***G6 PD deficiency*** - **Glucose-6-phosphate dehydrogenase (G6PD) deficiency** is an **X-linked recessive** inherited disorder [1]. - Males are predominantly affected as they have only one X chromosome, and a defective gene on it will manifest the disease. *Hypogammaglobulinemia* - This is a broad term for reduced gamma globulins and can have various genetic causes, including **X-linked agammaglobulinemia (Bruton's agammaglobulinemia)**, which is indeed X-linked. However, without further specification, hypogammaglobulinemia alone doesn't definitively point to a sex-linked inheritance as other forms exist. - Other forms of hypogammaglobulinemia, such as **common variable immunodeficiency (CVID)**, can have autosomal dominant or autosomal recessive inheritance patterns or be sporadic. *Diamond-Blackfan anemia* - This is a rare **congenital hypoplastic anemia** primarily inherited in an **autosomal dominant** pattern, though some cases are sporadic. - It is caused by mutations in ribosomal protein genes, and its inheritance is not typically sex-linked. *Down syndrome* - **Down syndrome** (Trisomy 21) is a **chromosomal disorder** caused by the presence of an extra copy of chromosome 21. - It is not a sex-linked inherited disease because it involves an **autosomal chromosome**, not a sex chromosome (X or Y).

Question 238: Which is wrong about Crigler-Najjar syndrome Type-1?

A. Kernicterus is usual.
B. Hepatic histology is normal.
C. Very high level of unconjugated bilirubin occurs in neonatal period.
D. It responds well to phenobarbital. (Correct Answer)

Explanation: ***It responds well to phenobarbital.*** - **Crigler-Najjar syndrome Type 1** is characterized by a complete or near-complete absence of **UGT1A1 enzyme activity**, meaning there is no enzyme for phenobarbital to induce [1]. - Therefore, **phenobarbital** treatment, which works by inducing this enzyme, is ineffective in Type 1 [1]. *Kernicterus is usual.* - Due to the severe deficiency of **UGT1A1**, **unconjugated bilirubin** builds up to dangerously high levels, leading to **kernicterus** (bilirubin encephalopathy) in untreated infants [1]. - This neurological damage is a hallmark and often fatal complication of Crigler-Najjar Type 1 [1]. *Hepatic histology is normal.* - The primary defect in Crigler-Najjar Type 1 is a **functional enzyme deficiency**, not a structural one. - Thus, the liver cells themselves appear normal under microscopy, as there is no overt damage or inflammation. *Very high level of unconjugated bilirubin occurs in neonatal period.* - The complete or nearly complete absence of **UGT1A1** results in a severe inability to conjugate bilirubin, leading to extremely high levels of **unconjugated bilirubin** from birth [1]. - This presents as severe **neonatal jaundice**, which is persistent and life-threatening [1].

Question 239: A 22-year-old man complains about his inability to conceive a child. On physical examination, the patient is noted to be tall (6 ft, 5 in) and exhibits gynecomastia and testicular atrophy. Laboratory studies demonstrate increased serum levels of follicle-stimulating hormone. Cytogenetic studies reveal a chromosomal abnormality. What is the most common cause of this patient's chromosomal abnormality?

A. Chromosomal instability during cell division
B. Failure of chromosome separation during gamete formation (Correct Answer)
C. Structural rearrangement of chromosomes
D. Chromosomal translocation during meiosis

Explanation: ***Failure of chromosome separation during gamete formation*** - The patient's symptoms (tall stature, gynecomastia, testicular atrophy, infertility, and elevated FSH) are classic for **Klinefelter syndrome**, which is characterized by a **47,XXY karyotype** [1]. - This extra X chromosome most commonly arises from **nondisjunction** (failure of homologous chromosomes or sister chromatids to separate) during **meiosis I** in the mother or, less frequently, during meiosis I or II in the father, or post-zygotic mitotic nondisjunction. *Chromosomal instability during cell division* - This typically refers to a general propensity for cells to acquire chromosomal aberrations, often seen in cancers or specific genetic syndromes like **Fanconi anemia** or **Bloom syndrome**. - While it can lead to chromosomal abnormalities, it is not the primary mechanism behind the specific 47,XXY aneuploidy seen in Klinefelter syndrome. *Chromosomal translocation during meiosis* - **Translocations** involve the exchange of genetic material between non-homologous chromosomes. - While translocations can cause genetic disorders, they result in a quantitative change in genetic material (e.g., partial trisomy or monosomy), not the extra whole sex chromosome characteristic of Klinefelter syndrome. *Structural rearrangement of chromosomes* - This is a broad category that includes deletions, duplications, inversions, and translocations, all of which alter the arrangement of genetic material within or between chromosomes. - While an extra chromosome is a type of chromosomal abnormality, the mechanism of nondisjunction leading to an entire extra chromosome (like an extra X) is a more specific and accurate description for the cause of **Klinefelter syndrome** [1], [2].

Question 240: Chloride receptor defect is responsible for:

A. Cystic fibrosis (Correct Answer)
B. Alpha-1 antitrypsin deficiency
C. Wilson's disease
D. Hemochromatosis

Explanation: Cystic fibrosis - Cystic fibrosis (CF) is caused by mutations in the **CFTR gene**, which encodes the **cystic fibrosis transmembrane conductance regulator protein**, a **chloride channel** [1]. - A defective CFTR protein leads to abnormal chloride transport across epithelial cells, resulting in thick, viscous secretions in various organs like the lungs, pancreas, and sweat glands [1]. *Alpha-1 antitrypsin deficiency* - This condition is due to a genetic defect in the production of **alpha-1 antitrypsin**, a protective enzyme. - It primarily affects the lungs (emphysema) and liver (cirrhosis) and is not related to chloride receptor function. *Wilson's disease* - Wilson's disease is an autosomal recessive disorder characterized by accumulation of **copper** in various tissues, especially the liver, brain, and eyes. - It is caused by mutations in the **ATP7B gene**, which codes for a copper-transporting ATPase, not a chloride channel. *Hemochromatosis* - Hemochromatosis is a disorder of **iron overload** in the body, primarily due to excessive absorption of dietary iron. - It is often caused by mutations in the **HFE gene** and does not involve chloride receptor defects.

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