Pediatric Genetic Syndromes and Dysmorphology (Detailed) MCQs

Pediatrics · 42 free questions with answers & explanations.

1. A 12-year-old boy is referred for tall stature, long limbs, arachnodactyly, pectus excavatum, lens dislocation (upward), and aortic root dilation of 4.2 cm. Molecular testing confirms FBN1 mutation. Which additional systemic feature requires URGENT monitoring?
2. A 3-year-old boy has coarse facial features, corneal clouding, hepatosplenomegaly, developmental regression, kyphosis, and umbilical hernia. Urine shows increased dermatan and heparan sulphate. Enzyme assay shows absent α-L-iduronidase. Which disorder is this?
3. A 15-year-old girl has primary amenorrhoea, short stature (147 cm), webbing of the neck, wide carrying angle, shield chest, and bicuspid aortic valve. Karyotype is 45,X. Which additional complication should be screened for regularly?
4. A child with prader-Willi syndrome is identified by DNA methylation analysis showing absence of paternal 15q11-q13 expression. Which of the following is the mechanism in approximately 25% of cases?
5. A 2-year-old girl presents with short stature, webbing of neck, widely spaced nipples, cubitus valgus, and widely spaced eyes. Karyotype shows 45,X. Echocardiography should be routinely performed as this karyotype is associated with which specific cardiac defect at highest risk?
6. A 6-month-old boy has coarse facial features, cloudy corneas, organomegaly, and skeletal dysplasia (dysostosis multiplex on X-ray). Urine shows elevated heparan sulfate and dermatan sulfate. Enzyme assay confirms deficiency of iduronate-2-sulfatase. This is:
7. A 3-year-old is referred for global developmental delay, hypotonia, and characteristic facial features: high forehead, widely spaced eyes, epicanthal folds, a flat nasal bridge, and a prominent philtrum. He has cryptorchidism and short stature. Chromosomal microarray shows deletion at 22q11.2. Which clinical feature is NOT typically associated with this deletion syndrome?
8. A newborn has macroglossia, omphalocele, hemihypertrophy, and birth weight 4.8 kg. Neonatal blood glucose is persistently 28 mg/dL despite feeds. The diagnosis is Beckwith-Wiedemann syndrome (BWS). The most important surveillance protocol for this child is:
9. A 2-year-old girl presents with sparse hair, recurrent infections, absent lymph nodes, and absent tonsils. Immunological workup reveals absent T and B cells. Genetic testing identifies an ADA gene mutation. Which treatment offers the possibility of curative therapy?
10. A 3-year-old child has short stature, proximal limb shortening (rhizomelia), a large head with frontal bossing, midface hypoplasia, and trident hand. Intelligence is normal. Spinal stenosis is a known complication. Molecular diagnosis reveals a gain-of-function mutation in FGFR3. What is the inheritance pattern?
11. An 8-year-old boy presents with progressive proximal muscle weakness, pseudohypertrophy of calves, and markedly elevated CK (8000 U/L). Genetic testing reveals a frameshift deletion in exons 48–52 of the DMD gene causing a premature stop codon. Which molecular therapy targets this specific mutation mechanism?
12. A neonate has microcephaly, prominent occiput, overlapping fingers (index over middle, fifth over fourth), rocker-bottom feet, ventricular septal defect, and omphalocele. Chromosomal analysis would most likely show:
13. A 5-year-old boy has a history of paternal grandmaternal intellectual disability. He has macro-orchidism, prominent ears, large jaw, and an IQ of 55. His mother is phenotypically normal but a carrier. The responsible mutation is best described as:
14. A 6-month-old boy presents with progressive macrocephaly, coarse facial features, hepatosplenomegaly, and corneal clouding. Urinary glycosaminoglycans (heparan sulfate and dermatan sulfate) are markedly elevated. Enzyme assay confirms alpha-L-iduronidase deficiency. What is this diagnosis and what is the MAJOR distinguishing feature between Hurler (MPS IH) and Scheie (MPS IS) syndrome?
15. A 3-year-old girl is evaluated for short stature, webbed neck, widely spaced nipples, and primary amenorrhea is anticipated. Karyotype is 45,X. Regarding Turner syndrome, which cardiac anomaly is MOST common and which is MOST life-threatening?
16. A 2-year-old boy presents with self-mutilation (biting his fingers and lips to the point of tissue destruction), intellectual disability, choreoathetosis, and hyperuricemia. Serum uric acid is 11.4 mg/dL. What is the molecular defect responsible for this condition?
17. A 4-month-old infant with delayed developmental milestones is evaluated. He has a cherry-red spot on fundoscopy, exaggerated startle response to sound (hyperacusis), progressive neurological deterioration, and macrocephaly. Parents are Ashkenazi Jewish. Hexosaminidase A activity is undetectable. Which diagnosis is this and what is the inheritance pattern?
18. A newborn with hypotonia, feeding difficulties, and a distinctive facial phenotype (flat face, upslanting palpebral fissures, epicanthal folds, single palmar crease) is confirmed to have trisomy 21. Which of the following is the MOST common cause of death in Down syndrome children beyond infancy?
19. A 6-month-old male infant has large testes, prominent ears, a long narrow face, and macrocephaly. His mother mentions that his maternal uncle was intellectually disabled and had similar facial features. CGG repeat analysis reveals 230 repeats in the FMR1 gene. Which statement best describes the inheritance pattern?
20. A newborn has a webbed neck, widely spaced nipples, peripheral edema of the hands and feet, low posterior hairline, coarctation of the aorta, and horseshoe kidney on ultrasound. Karyotype is 45,X. Which feature is MOST specific to this condition compared to Noonan syndrome?
21. A 3-year-old is brought with hypopigmented macules on the trunk, ash-leaf spots, shagreen patches on the back, and multiple periungual fibromas. He has seizures since 6 months of age and is hyperactive with attention problems. Brain MRI reveals cortical tubers. This condition is associated with mutations in which genes?
22. A 14-month-old boy has severe intellectual disability, absent speech, inappropriate happy demeanor with frequent laughter, characteristic puppet-like ataxic gait, seizures with a characteristic EEG pattern, and hypopigmentation compared to siblings. Molecular testing reveals absence of maternal UBE3A expression. What is the epigenetic mechanism in the majority of cases?
23. A 2-year-old boy is evaluated for severe intellectual disability, self-injurious behavior (lip and finger biting causing mutilation), hyperuricemia, and gout-like arthropathy. Enzymatic assay reveals near-absent hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity. What is the inheritance pattern and primary metabolic consequence?
24. A newborn is noted to have a single palmar crease, upslanting palpebral fissures, epicanthal folds, protruding tongue, and hypotonia. Cardiac examination reveals a grade 3/6 systolic murmur. Karyotype confirms trisomy 21. Which cardiac lesion is the MOST commonly associated with Down syndrome?
25. A 6-year-old boy has a long face, large ears, macroorchidism, and intellectual disability. His maternal grandfather also had cognitive issues. Cytogenetic analysis reveals an expanded CGG trinucleotide repeat in the FMR1 gene. This is consistent with:
26. A neonate has a 'cat cry' at birth, microcephaly, low birth weight, epicanthal folds, and wide-set eyes. Chromosomal microarray confirms a deletion of chromosome 5p. This condition is:
27. A child presents with short stature, webbed neck, widely spaced nipples, and failure of pubertal development at age 14. Karyotype is 45,X. Which of the following is the MOST common cardiac anomaly in this condition?
28. A 2-year-old boy has ash-leaf macules, a shagreen patch, and infantile spasms that started at 4 months of age. MRI of the brain shows cortical tubers and subependymal nodules. This syndrome is associated with mutations in which genes?
29. A 3-year-old presents with severe intellectual disability, absent speech, inappropriate laughter, seizures, and ataxic gait. EEG shows characteristic high-amplitude delta waves with superimposed spike discharges. Genetic testing reveals a deletion of the maternal chromosome 15q11-q13. The diagnosis is:
30. A 3-year-old boy is referred for global developmental delay, absent speech, happy demeanor with frequent unprovoked laughter, seizures (particularly myoclonic), and ataxic gait. EEG shows large amplitude spike-wave discharges. Which genetic mechanism is responsible for THIS specific syndrome?
31. A 2-year-old girl is brought with recurrent pneumonias, eczematous rash, thrombocytopenia with small platelets on blood film, and elevated IgA and IgE but markedly low IgM. She has a maternal uncle who died in childhood with similar symptoms. Which gene is most likely mutated?
32. A newborn with hypotonia, single palmar crease, flat facial profile, upward slanting palpebral fissures, and a large tongue is suspected to have trisomy 21. The karyotype shows 46 chromosomes with a derivative chromosome between 14 and 21. What is the mechanism and the recurrence risk implication?
33. A boy aged 14 presents with tall stature, small firm testes, gynecomastia, and reduced body/facial hair. His IQ is borderline normal. Karyotype would most likely show:
34. An 18-month-old boy with coarse facial features, corneal clouding, skeletal dysplasia (dysostosis multiplex), hepatosplenomegaly, and recurrent respiratory infections is suspected to have a lysosomal storage disorder. Enzyme assay confirms alpha-L-iduronidase deficiency. This child most likely has:
35. A 3-year-old girl has a history of microcephaly, severe intellectual disability, happy demeanor with inappropriate laughter, absence/atonic seizures, and absent speech. EEG shows characteristic high-amplitude slow spikes. The genetic mechanism is:
36. A 2-year-old boy has macrocephaly, macro-orchidism, prominent ears, mild-to-moderate intellectual disability, and a history of otitis media. His maternal grandfather had mild cognitive impairment and tremor. The most likely diagnosis and inheritance pattern is:
37. A child with multiple café-au-lait macules (8 in number, >5 mm each), axillary freckling, and 2 Lisch nodules is diagnosed with neurofibromatosis type 1. The minimum number of café-au-lait spots required as a diagnostic criterion (without other features) in a prepubertal child is:
38. A neonate is born with hypotonia, feeding difficulty, almond-shaped eyes, small hands and feet, and cryptorchidism. He later develops hyperphagia and obesity. The chromosomal mechanism responsible for this condition is:
39. A 6-year-old girl with short stature, webbed neck, widely spaced nipples and primary amenorrhea in adolescence is found to have karyotype 45,X. The most important investigation to perform routinely in this condition is:
40. A child with Williams syndrome presents with short stature, elfin facies, gregarious personality, and hypercalcemia in infancy. On echocardiography, the most characteristic cardiac lesion expected is:
41. An 18-month-old boy has tall stature, macro-orchidism, and intellectual disability. His maternal grandfather had tremor and ataxia. His mother has premature ovarian insufficiency. The most likely molecular diagnosis is:
42. A neonate has cleft palate, hypocalcemia (tetany), absent thymus, and truncus arteriosus on echocardiography. The chromosomal abnormality most likely to be detected on FISH analysis is: