KMU Past Paper Practice
TOPIC 6. Clinical Genetics, Chromosomal & Connective Tissue Disorders
20 A-Type Single Best Answer MCQs | Context-Rich Clinical Reasoning | MS Module
Original KMU-style practice questions. Not represented as verbatim questions from previous KMU examinations.
MCQ 1
Question:
A couple has experienced three early pregnancy losses. The woman has a normal clinical examination, but chromosome analysis reveals a structural rearrangement. Her karyotype contains 46 chromosomes, and no major loss of genetic material is detected. The clinician explains that the rearrangement may nevertheless affect reproduction. Which reproductive outcome is most directly associated with this finding?
Options:
Progressive maternal loss of functional X chromosomes
Complete failure of meiotic chromosome replication
Autosomal dominant transmission of all rearranged genes
Permanent suppression of embryonic cell division
Production of gametes with unbalanced chromosome complements
MCQ 2
Question:
A newborn has developmental abnormalities and a chromosome count of 46. Detailed chromosome analysis demonstrates that a segment of one chromosome is missing. The parents ask why the child has a genetic disorder despite having the normal total number of chromosomes. Which abnormality best explains the findings?
Options:
Complete autosomal trisomy
Balanced chromosomal inversion
Segmental chromosomal deletion
Whole-genome polyploidy
Segmental chromosomal deletion
MCQ 3
Question:
A 26-year-old man with a hereditary connective tissue disorder has no similarly affected relatives. Genetic testing identifies a pathogenic FBN1 variant. Both parents undergo targeted testing and neither carries the identified variant in the tested tissues. Which explanation is most consistent with this family history?
Options:
A de novo pathogenic variant
Obligate paternal inheritance
Polygenic environmental inheritance
An acquired chromosomal trisomy
A de novo pathogenic variant
MCQ 4
Question:
A 35-year-old man has a confirmed X-linked dominant genetic disorder. His wife is unaffected, and the couple asks which children could inherit his pathogenic X-chromosome variant. Assuming the usual XX/XY chromosomal pattern, which outcome is expected?
Options:
All children inherit the variant irrespective of sex
All sons and half of daughters inherit the variant
Half of sons and half of daughters inherit the variant
All daughters and none of his sons inherit the variant
All daughters and none of his sons inherit the variant
MCQ 5
Question:
A family has several relatives with hypertension. Some develop the disease in early adulthood, whereas others remain normotensive despite having affected parents. The clinician explains that several inherited susceptibility factors interact with dietary salt intake, obesity and physical activity. Which concept best explains the absence of a fixed Mendelian recurrence ratio?
Options:
Complete X-linked recessive transmission
Combined effects of multiple genes and environment
Exclusive inheritance through the paternal Y chromosome
A chromosomal deletion shared by every affected relative
Combined effects of multiple genes and environment
MCQ 6
Question:
A newborn has clinical findings suggestive of Down syndrome. Chromosome analysis identifies an additional chromosome 21 in every sampled cell, without a structural translocation. The parents have normal karyotypes and no family history of the disorder. Which explanation is most appropriate regarding the usual origin of this abnormality?
Options:
Transmission of two recessive variants from carrier parents
Duplication of a short segment within the FBN1 gene
Inherited balanced inversion of the X chromosome
Loss of a chromosome after complete embryonic development
Failure of chromosome separation during gamete formation
MCQ 7
Question:
A newborn with Down syndrome has poor feeding and increased respiratory effort. Examination reveals tachypnea, hepatomegaly and a cardiac murmur. Echocardiography demonstrates a complete atrioventricular septal defect with significant left-to-right shunting. Which complication most directly explains the progressive respiratory and feeding difficulties?
Options:
Isolated systemic hypertension
Primary myocardial infarction
Pulmonary overcirculation with heart failure
Acute obstruction of the aortic arch
Pulmonary overcirculation with heart failure
MCQ 8
Question:
A 4-year-old child with Down syndrome has poor weight gain and longstanding constipation. During routine evaluation, the pediatrician considers several associated conditions. The parents report that the child also becomes sleepy during the daytime and snores loudly at night. Which associated disorder most directly explains the sleep-related complaints?
Options:
Obstructive sleep apnea
Acute lymphoblastic leukemia
Atrioventricular septal defect
Sensorineural hearing loss
Obstructive sleep apnea
MCQ 9
Question:
A child is diagnosed with Down syndrome due to a Robertsonian translocation. The cytogenetic report shows extra chromosome 21 material attached to chromosome 21. Further testing reveals that one parent carries a balanced Robertsonian translocation involving both chromosome 21 homologues. Which counselling issue is particularly important?
Options:
The disorder will necessarily become milder in later pregnancies
The recurrence risk is identical to sporadic free trisomy 21
The next child can be diagnosed using serum thyroid testing alone
The recurrence risk may be extremely high in future viable pregnancies
The recurrence risk may be extremely high in future viable pregnancies
MCQ 10
Question:
A 21-year-old man is investigated for tall stature, pectus deformity and long slender fingers. His father has similar findings. Ophthalmological examination identifies lens displacement, and echocardiography demonstrates aortic root enlargement. Which structural protein is most directly implicated in the underlying disorder?
Options:
Type II collagen
Type IV collagen
Dystrophin
Beta-globin
Fibrillin-1
MCQ 11
Question:
A patient with Marfan syndrome undergoes echocardiography because of exertional fatigue and palpitations. The examination reveals aortic root enlargement associated with aortic regurgitation. Which mechanism most directly explains the development of valvular incompetence?
Options:
Excessive calcification of the aortic valve leaflets
Dilatation of the aortic root preventing effective leaflet coaptation
Congenital narrowing of the left ventricular outflow tract
Obstruction of the coronary circulation by arterial thrombosis
Dilatation of the aortic root preventing effective leaflet coaptation
MCQ 12
Question:
A 27-year-old woman with Marfan syndrome wishes to participate in competitive weightlifting. Previous echocardiography demonstrated a mildly enlarged aortic root. She has no current symptoms and believes exercise is safe because she feels well. Which counselling recommendation is most appropriate?
Options:
Avoid all forms of physical activity indefinitely
Recommend high-intensity training to improve aortic wall strength
Advise against heavy straining and arrange individualized cardiovascular exercise guidance
Begin routine anticoagulation before competitive exercise
Advise against heavy straining and arrange individualized cardiovascular exercise guidance
MCQ 13
Question:
A 6-year-old child is evaluated for recurrent low-trauma fractures and abnormal tooth development. Examination reveals blue sclerae and lower-limb deformities. The pediatrician explains that the affected protein normally provides tensile strength to bone. Which extracellular matrix component is primarily abnormal in the common classical forms of this condition?
Options:
Type I collagen fibers
Type IV collagen networks
Elastin alone
Cartilage proteoglycans alone
Type I collagen fibers
MCQ 14
Question:
A 16-year-old girl has generalized joint hypermobility, unusually elastic skin and widened atrophic scars following minor injuries. Her skeletal radiographs are normal, and she has no history of recurrent fractures. Which feature best differentiates her likely inherited connective tissue disorder from osteogenesis imperfecta?
Options:
Occurrence during childhood or adolescence
Association with abnormalities of connective tissue
Possible involvement of collagen-related proteins
Predominant skin hyperextensibility and tissue fragility
Predominant skin hyperextensibility and tissue fragility
MCQ 15
Question:
A 13-year-old boy has persistent hematuria and mild proteinuria. His maternal uncle developed chronic kidney disease and hearing impairment during early adulthood. The child has recently developed difficulty hearing speech in the classroom. Which structural abnormality best explains the renal manifestations of the suspected inherited disorder?
Options:
Excessive fibrillin deposition in renal tubules
Defective type IV collagen in the glomerular basement membrane
Reduced type I collagen production in renal interstitial bone matrix
Inherited destruction of glomeruli by circulating immune complexes
Defective type IV collagen in the glomerular basement membrane
MCQ 16
Question:
A 37-year-old pregnant woman has an increased-risk first-trimester screening result for trisomy 21. She asks whether the screening result alone is sufficient to make an irreversible reproductive decision. The obstetrician explains that further testing can examine fetal genetic material. Which principle is most appropriate?
Options:
Treat the screening probability as an established fetal diagnosis
Repeat maternal age estimation as the definitive investigation
Perform routine fetal growth measurement instead of genetic assessment
Explain that all chromosome abnormalities can be excluded by ultrasound
Obtain informed consent and discuss confirmatory diagnostic testing
MCQ 17
Question:
A woman at 12 weeks of pregnancy is referred because a previous child had an inherited chromosomal disorder. She asks about obtaining an early prenatal diagnostic sample. During counselling, the obstetrician explains that the relevant procedure obtains placental tissue rather than amniotic fluid. Which procedure is being described?
Options:
Maternal serum screening
Fetal echocardiography
Chorionic villus sampling
Second-trimester amniocentesis
Chorionic villus sampling
MCQ 18
Question:
A couple has a previous child affected by a confirmed autosomal recessive genetic disorder. The familial pathogenic variants are known. During their next pregnancy, an invasive fetal sample is obtained for prenatal diagnosis. Which testing strategy most directly establishes whether the fetus inherited the disease-causing variants?
Options:
Targeted molecular analysis of fetal DNA
Routine obstetric ultrasonography
Fetal blood group determination
Maternal complete blood count
Targeted molecular analysis of fetal DNA
MCQ 19
Question:
A 24-year-old woman attends premarital screening. She has mild microcytic anemia, a relatively high red-cell count and elevated HbA2. Her prospective partner reports that his younger brother requires regular blood transfusions for beta-thalassemia major. Which next step is most appropriate for assessing the couple’s reproductive risk?
Options:
Reassure the couple that mild maternal anemia excludes genetic risk
Delay all screening until the woman becomes pregnant
Test only the affected brother rather than the prospective partner
Perform appropriate thalassemia carrier testing of the prospective partner
Perform appropriate thalassemia carrier testing of the prospective partner
MCQ 20
Question:
A couple with a family history of thalassemia receives genetic counselling. The clinician explains the inheritance pattern and available testing options. The husband’s relatives insist that the clinician disclose the couple’s genetic findings and make a marriage decision on their behalf. Which response best reflects appropriate genetic counselling practice?
Options:
Recommend compulsory avoidance of marriage between carriers
Respect confidentiality and support the couple’s informed voluntary decisions
Withhold recurrence-risk information to prevent unnecessary anxiety
Allow the family’s senior member to decide on reproductive testing
Respect confidentiality and support the couple’s informed voluntary decisions