Chromosomal Disorders and Other Genetic Diseases MCQs

Ans. is 'c' i.e., Accumulation of very long chain fatty acids [Ref Harper 29m/e p. 554; Chatterjea 6th le p. 412] Zellweger Syndrome is a rare inborn error of peroxisomal fatty acid oxidation° due to absence of functional peroxisomes in all tissues. As a result, the long chain fatty acids are not oxidized in peroxisomes and accumulate in tissues particularly in brain, liver, kidney and muscle and usually result in death by age six.

Disease:- Familial hypercholesterolemia (type IIa) Defect:- Defective LDL receptors or mutation in ligand region of apo B-100. Remarks:- Elevated LDL levels and hypercholesterolemia, resulting in atherosclerosis and coronary disease. Reference: Harper's illustrated biochemistry 32 nd edition, page 275

Explanation: Micrognathia (small jaw) and low-set ears are classic dysmorphic features seen in several chromosomal deletion syndromes, such as: Cri-du-chat syndrome (5p deletion) Wolf -Hirschhorn syndrome (4p deletion) 2 deletion syndrome (DiGeorge syndrome) 13q deletion syndrome T Translocations, inversions, or amplifications may also cause genetic disorders, but specific features like micrognathia and low-set ears are most characteristically seen with deletions. (option B, C, D) Key Takeaways: Deletions consistently produce the distinct facial dysmorphisms (micrognathia, low-set ears) due to loss of developmental genes. References: https://pmc.ncbi.nlm.nih.gov/articles/PMC4736720/ https://www.ncbi.nlm.nih.gov/books/NBK1523/?utm_source=chatgpt.com https://www.ncbi.nlm.nih.gov/books/NBK1183/

Answer- D. Cytogenetic abnormalities Most common cause of female pseudohermaphroditism - CAH due to 21 hydroxylase deficiency. Most common cause of male pseudohermaphroditism - Gonadal dysgenesis and defect in androgen action.

Fragile X syndrome is the prototype of diseases in which the causative mutation occurs in a long repeating sequence of three nucleotides. Fragile X syndrome results from a mutation in the FMR1 gene, which maps to Xq27.3 and is the second most common genetic cause of mental retardation, after Down syndrome. The typical physical phenotype includes a long face with a large mandible, large everted ears and large testicles(macroorchidism). Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th ed Pg: 269

Anticipation refers to the phenomenon whereby clinical features of fragile X syndrome worsen with each successive generation, as if the mutation becomes increasingly deleterious as it is transmitted from a man to his grandsons and great-grandsons. Reference: Robbins and Cotran Pathologic Basis of Diseases, 10 th ed Pg: 269

Explanation: Mitochondrial diseases follow maternal inheritance , meaning they are exclusively passed down from the mother to all of her children . This is because mitochondria are inherited only from the oocyte (egg) , as sperm mitochondria are typically degraded after fertilisation. (Option B, C and D ruled out) Thus, individuals inherit mitochondrial DNA (mtDNA) exclusively from their mother , and mutations in mtDNA result in mitochondrial disorders. Key Features of Mitochondrial Inheritance: Only mothers pass the disease to offspring. Both males and females can be affected , but only females transmit it. Affected males do not pass the condition to their children. Key Takeaway: Mitochondrial diseases are inherited exclusively from the mother , meaning both males and females can be affected , but only females pass the disease to the next generation .

Neurofibromatosis type 1 (NF-1) is characterized by the development of multiple neurofibromas and pigmented skin lesions. Neurofibromas are most numerous in the dermis but also may occur in visceral organs. Patients with NF-1 also may develop a type of sarcomatous neoplasm known as a malignant peripheral nerve sheath tumor (MPNST). NF-1 is a tumor suppressor that appears with an autosomal dominant pattern of inheritance, though some cases result from spontaneous new mutations (no prior family members with the mutation). NF-1 exhibits variable expressivity, because the manifestations (location and types of neoplasms) are not the same in all patients. The other forms of inheritance listed are not associated with tumor suppressor genes. Reference: Robins Basic Pathology 10th ed/pg 245