Genetic and Chromosomal Disorders MCQs

Pathology · 83 free questions with answers & explanations.

1. A newborn with normal karyotype presents with hypotonia, small hands and feet, almond-shaped eyes, and later develops hyperphagia and obesity. Molecular analysis shows deletion on the paternal chromosome 15q11-q13. The mechanism explaining why the same deletion on the maternal chromosome produces a completely different phenotype (Angelman syndrome) is:
2. A 25-year-old woman with Marfan syndrome is found to have aortic root dilation. The molecular defect in Marfan syndrome involves which protein, and how does this defect mechanistically cause cardiovascular manifestations?
3. Prader-Willi and Angelman syndromes both result from abnormalities of chromosome 15q11-q13 but have distinct phenotypes. Prader-Willi syndrome arises when the deleted or inactivated chromosome 15q11-q13 region is of which parental origin?
4. Fragile X syndrome is the most common inherited cause of intellectual disability. The FMR1 gene mutation involves expansion of a CGG trinucleotide repeat in the 5' UTR. When repeat count exceeds which threshold does full mutation with methylation and gene silencing occur?
5. A 3-year-old boy with an 'angelman-like' phenotype (seizures, intellectual disability, happy demeanor) is found NOT to have a deletion at 15q11-q13 on FISH. Methylation analysis shows two copies of paternal methylation pattern at the SNRPN locus. What is the diagnosis?
6. A 28-year-old woman with a history of preterm birth to an infant with hypotonia and feeding difficulties is counseled about recurrence risk. Prenatal testing reveals the fetus has inv(15)(p11q13) — a pericentric inversion. Which molecular mechanism determines whether this fetus has Prader-Willi syndrome?
7. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) both result from loss of function of genes on chromosome 15q11-q13, yet they produce entirely different phenotypes. The molecular mechanism underlying this parent-of-origin difference is:
8. A newborn with ambiguous genitalia, mild electrolyte abnormalities (hyponatremia, hyperkalemia), and hyperpigmentation is evaluated. 17-OH progesterone is markedly elevated. The most common enzyme deficiency causing this presentation is:
9. A child with Angelman syndrome was found to have uniparental disomy (UPD) of chromosome 15 — both copies derived from the father. Why does paternal UPD of chromosome 15 cause Angelman syndrome rather than Prader-Willi syndrome?
10. A 30-year-old man with Marfan syndrome carries a heterozygous missense FBN1 mutation. The mutant fibrillin-1 causes disease through a dominant-negative mechanism. This means:
11. Prader-Willi syndrome and Angelman syndrome affect the same chromosomal region (15q11-q13) but cause distinct phenotypes based on the parental origin of the deletion. This phenomenon is explained by:
12. Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene encoding neurofibromin. Neurofibromin functions as a:
13. A female infant is born with Turner syndrome (45,X). Which of the following mechanisms best explains the characteristic webbed neck (pterygium colli) and cystic hygroma seen in Turner syndrome?
14. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by abnormalities involving the same region of chromosome 15q11-q13 but show DIFFERENT clinical phenotypes based on parental origin. A child with severe intellectual disability, seizures, happy demeanor, and ataxic gait has Angelman syndrome. The molecular mechanism is:
15. A 2-year-old boy has intellectual disability and a 'cat cry' at birth. Chromosomal microarray shows a deletion of the short arm of chromosome 5 (del 5p). This is Cri-du-chat syndrome. The 'cat-like' cry is caused by:
16. Prader-Willi syndrome and Angelman syndrome are caused by imprinting defects at chromosome 15q11-q13. Which molecular mechanism specifically causes Prader-Willi syndrome?
17. A newborn with severe intellectual disability, microcephaly, and a high-pitched (cat-like) cry has cytogenetics showing deletion of chromosome 5p. What is this syndrome?
18. A 16-year-old girl with Turner syndrome (45,X) has elevated FSH, streak gonads, and primary amenorrhea. The gonadal failure is caused by:
19. A neonate with congenital heart defect, ambiguous genitalia, and rocker-bottom feet undergoes chromosomal analysis showing 47,XY,+18. Which cardiac defect is MOST characteristic of trisomy 18 (Edwards syndrome)?
20. Genetic testing in a family shows a 10-year-old male with intellectual disability, macroorchidism, and elongated facies has 300 CGG repeats in the FMR1 gene. His mother has 90 CGG repeats. Why does the mother remain phenotypically unaffected despite carrying the mutation?
21. A 2-year-old girl presents with progressive loss of milestones after 12 months of apparently normal development, hand-wringing stereotypies replacing purposeful hand use, gait apraxia, and seizures. Genetic testing reveals MECP2 mutation on X chromosome. This syndrome occurs almost exclusively in females because:
22. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) both result from abnormalities of chromosome 15q11-q13. The specific mechanism producing PWS when the deletion or imprinting error occurs on the PATERNAL chromosome 15 is:
23. Marfan syndrome (MFS) is caused by FBN1 (fibrillin-1) mutation. The primary pathogenic mechanism of cardiovascular and skeletal manifestations in MFS, beyond structural weakness, is:
24. A child is born with hypotonia, intellectual disability, and short stature. Methylation-specific PCR of the 15q11-q13 region shows normal maternal methylation pattern but absence of the paternal unmethylated allele. FISH shows no deletion. What is the most likely mechanism and diagnosis?
25. Marfan syndrome results from fibrillin-1 (FBN1) mutations. Beyond weakening connective tissue scaffolding, which additional molecular mechanism links fibrillin-1 deficiency to aortic aneurysm formation?
26. Angelman syndrome and Prader-Willi syndrome both result from absence of the 15q11-q13 region but exhibit entirely different phenotypes. The molecular basis for this phenotypic difference is imprinting. Which of the following correctly states the gene expression pattern?
27. A newborn is found to have a small ring chromosome 15 detected by standard karyotype. Microarray analysis reveals absence of 15q11-q13 sequences on this ring chromosome. The phenotype most likely to result from this finding is:
28. A child is born with severe intellectual disability, absent speech, seizures and a happy demeanour with frequent laughter. Methylation analysis of the 15q11-q13 region shows a biparental methylation pattern — both alleles show paternal methylation pattern (no maternal methylation mark). FISH shows intact chromosome 15 on both homologues. What is the molecular diagnosis?
29. A couple has a child with cystic fibrosis (homozygous F508del). Both parents are carriers. On genetic counselling it is found that the maternal grandfather also has a child with CF from an unrelated first marriage. The grandfather is phenotypically normal. What is the probability that a subsequent child of the CF couple will be affected?
30. A neonate presents with low birth weight, overlapping fingers with clenched fists, rocker-bottom feet, cardiac defects, and severe intellectual disability. Chromosome analysis reveals trisomy 18. Which molecular mechanism underlying trisomy 18 (Edwards syndrome) differentiates it from trisomy 21 in terms of chromosomal origin?
31. Beckwith-Wiedemann syndrome (BWS) is caused by epigenetic or genetic abnormalities at chromosome 11p15.5. Which combination of mechanisms correctly describes the two imprinting control regions (ICR1 and ICR2) and the pathogenesis of overgrowth in BWS?
32. A 30-year-old woman with a family history of early-onset breast and ovarian cancer undergoes genetic testing. She is found to carry a BRCA1 pathogenic variant. BRCA1 protein functions in DNA repair primarily through:
33. In genomic imprinting disorders, Prader-Willi syndrome (PWS) and Angelman syndrome (AS) both involve chromosome 15q11-q13 but differ in parent-of-origin of deletion. The molecular basis for the parent-of-origin specificity is:
34. A child with Prader-Willi syndrome is found to have a deletion on chromosome 15q11-q13 on the PATERNAL chromosome. His sibling with the same 15q11-q13 deletion on the MATERNAL chromosome has Angelman syndrome. This demonstrates which genetic mechanism?
35. A female patient with Turner syndrome undergoes karyotyping showing 45,X. In Turner syndrome, which organ system abnormality is the leading cause of morbidity and mortality in adults?
36. A child is born with hypotonia, feeding difficulty, and almond-shaped eyes. At age 5, obesity and hyperphagia develop. Molecular testing shows maternal uniparental disomy (UPD) of chromosome 15 with two copies of maternal chromosome 15 and no paternal copy. Which syndrome results, and what is the critical imprinted region involved?
37. In trinucleotide repeat disorders, anticipation (worsening severity across generations) depends on which strand and which parent transmits the expanded allele. In Huntington disease (CAG repeat expansion in HTT), what is the pathological mechanism by which mutant huntingtin causes neuronal death in the striatum?
38. In Prader-Willi syndrome, the molecular mechanism involves maternal uniparental disomy (UPD) of chromosome 15 or paternal deletion of 15q11-q13. The critical genes silenced are:
39. A neonate with ambiguous genitalia, 46,XX karyotype, and elevated 17-hydroxyprogesterone is diagnosed with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The enzymatic block causes accumulation of substrate that is shunted to:
40. A 2-year-old child presents with hepatosplenomegaly, corneal clouding, and coarse facial features. Urine shows elevated heparan sulfate and dermatan sulfate. Which enzyme deficiency is responsible?
41. A child has normal intellectual development, tall stature, hyperextensible joints, aortic root dilatation, and lens subluxation superiorly and temporally. FBN1 gene mutation is identified. What is the underlying molecular defect in Marfan syndrome?
42. A female infant presents with webbed neck, broad chest, widely spaced nipples, and primary amenorrhea. Karyotype shows 45,X. Which cardiac defect is MOST commonly associated with Turner syndrome?
43. A male infant with intellectual disability, macroorchidism, elongated face, large ears, and hyperextensible joints is found to have a CGG trinucleotide repeat expansion in the 5' UTR of the FMR1 gene (>200 repeats) with hypermethylation silencing FMR1. This trinucleotide repeat disease demonstrates which inheritance pattern?
44. Prader-Willi syndrome and Angelman syndrome are both caused by deletions at 15q11-13 but present with completely different phenotypes depending on the parental origin of the deletion. This phenomenon is best explained by:
45. A newborn has hypotonia, flat facies, single palmar crease, and a cardiac defect. Karyotype shows 47 chromosomes. The MOST common mechanism causing this syndrome is:
46. Fragile X syndrome is caused by CGG trinucleotide repeat expansion in the 5' UTR of FMR1. When the repeat number exceeds 200 (full mutation), which epigenetic change silences FMR1?
47. A 16-year-old girl presents with primary amenorrhea, short stature, webbed neck, and coarctation of the aorta. Chromosomal analysis shows 45,X. Which cardiac defect is most commonly associated with this syndrome?
48. Fragile X syndrome is caused by expansion of a CGG trinucleotide repeat in the 5' UTR of the FMR1 gene. A premutation (55-200 repeats) in a female carrier can undergo further expansion to a full mutation (>200 repeats) during female meiosis — this is called:
49. Prader-Willi syndrome results from deletion of the paternal chromosome 15q11-q13 region. If instead the maternal 15q11-q13 region is deleted in the same chromosomal locus, the resulting clinical syndrome is:
50. Prader-Willi syndrome results from loss of paternal 15q11-q13. When the same region is deleted from the maternal chromosome, which syndrome results?
51. A child with von Hippel-Lindau (VHL) disease develops cerebellar haemangioblastoma. The VHL protein normally ubiquitinates which transcription factor to target it for proteasomal degradation?
52. A newborn girl with 45,X karyotype presents with webbed neck, lymphedema of hands and feet, and coarctation of the aorta. The lymphedema results from:
53. Genomic imprinting explains the difference in phenotype between Prader-Willi syndrome (PWS) and Angelman syndrome (AS), both involving chromosome 15q11-q13. PWS results from lack of paternal contribution of this region because:
54. A 3-year-old girl presents with progressive muscle weakness, a cherry-red spot on fundoscopy, hepatosplenomegaly, and neurodegeneration. Enzyme assay shows absent hexosaminidase A activity. The storage material accumulating is:
55. A 28-year-old presents with marfanoid habitus, downward lens dislocation, intellectual disability, and thromboembolism. Urinary nitroprusside test is positive. The enzyme deficiency responsible is:
56. A newborn has hypotonia, small mouth, almond-shaped eyes, and hypogonadism. Chromosomal analysis shows deletion of chromosome 15q11-q13 on the paternal chromosome. The diagnosis is:
57. A male infant with macroglossia, umbilical hernia, hypoglycemia, and hemihypertrophy is diagnosed with Beckwith-Wiedemann syndrome. This overgrowth disorder primarily results from dysregulation of imprinting at which chromosomal locus?
58. Fragile X syndrome, the most common inherited cause of intellectual disability in males, is caused by trinucleotide (CGG) repeat expansion in which gene, and the repeat number in a full mutation is:
59. A newborn has hypotonia, Brushfield spots, endocardial cushion defect, and simian crease. Karyotype shows trisomy 21. The risk of this condition increases with maternal age primarily because of:
60. Neurofibromatosis type 1 (NF1) involves mutation of the NF1 gene encoding neurofibromin. Neurofibromin functions as a tumor suppressor through which mechanism?
61. Genomic imprinting explains why Prader-Willi syndrome and Angelman syndrome both arise from deletion of 15q11-q13 yet have distinct phenotypes. Which statement is correct?
62. Trinucleotide repeat expansion causing disease by a toxic gain-of-function RNA mechanism (rather than loss of protein function) is best exemplified by:
63. A male infant is born with overlapping fingers (second over third, fifth over fourth), rocker-bottom feet, prominent occiput, and a ventricular septal defect. Karyotype shows 47, XY +18. The eponym for this syndrome is:
64. A 2-year-old child has recurrent infections, partial albinism, silver-gray hair, and large granules in neutrophils and NK cells on peripheral smear. The molecular defect is:
65. Deletion of the MATERNAL chromosome 15q11-q13 results in which syndrome?
66. A 2-year-old boy presents with recurrent infections, coarse facial features, corneal clouding, hepatosplenomegaly, and developmental regression. Enzyme assay confirms alpha-L-iduronidase deficiency. This lysosomal storage disorder is classified as:
67. Genomic imprinting explains why deletion of the same chromosomal region (15q11-q13) causes two entirely different syndromes. Prader-Willi syndrome results from loss of the PATERNAL copy, while Angelman syndrome results from loss of the MATERNAL copy. Which molecular mechanism is most directly responsible for this parent-of-origin effect?
68. A child presents with intellectual disability, elf-like facies, hypercalcemia, and a friendly 'cocktail party' personality. Genetic testing reveals deletion of the elastin gene region. This is consistent with:
69. Genomic imprinting explains why deletion of the same chromosome 15q11-q13 region causes different syndromes depending on parental origin. Maternal deletion at 15q11-q13 causes which syndrome?
70. A 3-year-old boy has global developmental delay, coarse facial features, hepatosplenomegaly, corneal clouding, and dysostosis multiplex on radiographs. Enzyme assay shows deficiency of alpha-L-iduronidase. Urine shows elevated dermatan sulfate and heparan sulfate. Which lysosomal storage disorder is this?
71. A 10-year-old girl is found to have Turner syndrome (45,X) on karyotype. Which cardiac defect is most commonly associated with this chromosomal abnormality?
72. Prader-Willi syndrome and Angelman syndrome are caused by abnormalities at the same chromosome 15q11-13 region but have completely different phenotypes depending on the parent of origin. Paternal uniparental disomy (UPD) of chromosome 15 would result in which syndrome?
73. A newborn with features of Marfan syndrome is found to have a mutation in the FBN1 gene encoding fibrillin-1. Beyond causing structural weakness of the extracellular matrix, fibrillin-1 deficiency contributes to Marfan pathogenesis through which additional molecular mechanism?
74. Fragile X syndrome is the most common inherited cause of intellectual disability. The molecular mechanism involves:
75. Prader-Willi syndrome results from loss of paternal chromosome 15q11–q13 (deletion or maternal uniparental disomy). The key concept explaining why maternal UPD causes the same phenotype as paternal deletion is:
76. A child presents with angelman syndrome — characterized by seizures, severe intellectual disability, inappropriate laughter, and absent speech. The genetic mechanism responsible in most cases is:
77. In neurofibromatosis type 1 (NF1), the NF1 gene product neurofibromin functions as:
78. A couple's child is born with thanatophoric dysplasia (lethal skeletal dysplasia). Neither parent has skeletal disease. Which of the following mechanisms best explains the high recurrence risk?
79. Fragile X syndrome results from CGG trinucleotide repeat expansion in the FMR1 gene. The molecular mechanism by which expansion silences FMR1 expression is:
80. Angelman syndrome and Prader-Willi syndrome both involve chromosome 15q11-q13 but differ in parent of origin. Angelman syndrome arises from:
81. Neurofibromatosis type 1 (NF1) gene encodes neurofibromin, a GTPase-activating protein. The tumor suppressor function of neurofibromin involves:
82. A 14-year-old girl of normal height presents with primary amenorrhoea, absent secondary sexual characteristics, webbed neck, and shield chest. Karyotype is 45,X. Which cardiac defect is most commonly associated with Turner syndrome?
83. A child presents with hepatosplenomegaly, Gaucher cells on bone marrow biopsy (macrophages with 'crumpled tissue paper' cytoplasm), and bone pain. Which enzyme is deficient?