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PE29.1-5 | Chromosomal Abnormalities — Practice Quiz
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A 3-month-old infant is brought to your OPD with hypotonia, upslanting palpebral fissures, a single palmar crease, and small ears. Chromosomal analysis shows 47,XX,+21 in all cells. Which mechanism is responsible in approximately 95% of Down syndrome cases?
Correct. Approximately 95% of Down syndrome arises from non-disjunction (usually during maternal meiosis I), producing trisomy 21 in all cells (47,XX,+21).
Three mechanisms cause Down syndrome: non-disjunction (~95%), Robertsonian translocation (~4%), and mosaicism (~1%). The mechanism determines recurrence risk and karyotype notation.
Non-disjunction during maternal meiosis I accounts for ~95% of Down syndrome. Robertsonian translocation accounts for ~4% and mosaicism ~1%.
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Karyotyping of a newborn with Down syndrome reveals 46 chromosomes; one chromosome 14 carries extra material from chromosome 21. The father's karyotype is normal. The mother's karyotype shows 45 chromosomes with a Robertsonian translocation 45,XX,der(14;21)(q10;q10). What is the empirical recurrence risk for Down syndrome in the next pregnancy?
Correct. When the mother carries a Robertsonian translocation t(14;21), the empirical recurrence risk for Down syndrome in the next pregnancy is approximately 10–15%.
Recurrence risk for Robertsonian translocation Down syndrome: maternal carrier ~10–15%, paternal carrier ~5%. Always karyotype both parents when translocation Down syndrome is identified.
For a maternal Robertsonian translocation carrier, empirical recurrence risk is ~10–15%; for a paternal carrier it is ~5%. These are lower than the theoretical 33% because many unbalanced gametes are non-viable.
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A 10-year-old boy with Down syndrome is referred for cardiac evaluation. He has a harsh pansystolic murmur, wide fixed split S2, and a diastolic rumble. Which cardiac defect is most characteristic of Down syndrome?
Correct. AVSD (complete endocardial cushion defect) is the most characteristic congenital heart defect in Down syndrome, occurring in ~40–50% of affected children.
AVSD is the most characteristic CHD in Down syndrome (~40–50%). All infants with Down syndrome need echocardiography at diagnosis. Other Down-associated conditions: duodenal atresia, hypothyroidism, ALL.
AVSD is the hallmark cardiac defect in Down syndrome (~40–50%). The murmur description (pansystolic + mid-diastolic rumble + fixed split S2) is classic for a large left-to-right shunt with AV valve regurgitation.
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During antenatal care at 16 weeks, a 37-year-old primigravida's maternal serum screening shows a low AFP, low uE3, and elevated hCG. The Down syndrome risk is reported as 1:80. Which is the MOST appropriate next step?
Correct. A risk of 1:80 (>1:250 threshold) on second-trimester triple screen warrants offering amniocentesis for definitive fetal karyotyping, after non-directive counselling.
Second-trimester triple screen (AFP↓, uE3↓, hCG↑) risk ≥1:250 is screen-positive for Down syndrome and warrants diagnostic amniocentesis after non-directive counselling.
A risk of 1:80 is a screen-positive result. Amniocentesis provides a definitive karyotype and is the appropriate next step after non-directive counselling.
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A paediatrician is reviewing the karyotype shown for a 6-month-old girl with dysmorphic features. The report reads: 45,X. She is short, with a webbed neck, widely spaced nipples, and shield chest. Which additional feature would MOST strongly support this diagnosis?
Correct. Bicuspid aortic valve is the most characteristic cardiac lesion in Turner syndrome (45,X), occurring in ~30% of patients. Coarctation of the aorta is also strongly associated.
Turner syndrome (45,X, NOT 45,XO) is associated with bicuspid aortic valve (~30%) and coarctation of the aorta (~10–15%). All patients need echocardiography and aortic imaging.
Bicuspid aortic valve and coarctation of the aorta are the hallmark cardiac lesions in Turner syndrome. VSD and AVSD are more characteristic of Down syndrome.
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A 14-year-old girl with Turner syndrome (45,X) has never had spontaneous puberty. FSH is markedly elevated. Which hormonal intervention is indicated?
Correct. Girls with Turner syndrome lack functional ovaries (streak gonads). Estrogen replacement, started at ~11–12 years at low dose and gradually increased, induces breast development and puberty. Progesterone is added 12–24 months later to allow uterine development and cyclical bleeds.
Turner syndrome = hypergonadotropic hypogonadism (FSH↑). Growth hormone for short stature (SHOX haploinsufficiency), estrogen for pubertal induction at 11–12 years. Fertility usually not possible with 45,X; donor egg IVF may be considered.
Turner syndrome causes ovarian dysgenesis. High FSH indicates hypergonadotropic hypogonadism. Treatment: low-dose estrogen from ~11–12 years, then cyclic progesterone added after 12–24 months.
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An 18-year-old male is referred for evaluation of infertility, small testes (3 mL each), and sparse body hair. He has gynaecomastia. FSH and LH are both markedly elevated; testosterone is low. Karyotype: 47,XXY. Which statement about his fertility management is MOST accurate?
Correct. In Klinefelter syndrome (47,XXY), testosterone replacement should be deferred until after TESE is attempted. Exogenous testosterone suppresses the pituitary–gonadal axis further, potentially eliminating any residual spermatogenesis.
Klinefelter syndrome (47,XXY): hypergonadotropic hypogonadism (FSH↑, LH↑, testosterone↓). TESE before testosterone replacement preserves fertility options. Testosterone from ~14 years for virilisation after fertility counselling.
TESE must be offered before testosterone replacement in Klinefelter syndrome. Some men have focal areas of spermatogenesis; testosterone given first suppresses even this residual function.
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A neonatologist is shown a karyotype with 46 chromosomes. One chromosome 14 appears larger than normal. Fluorescence in situ hybridisation (FISH) confirms chromosome 21 material attached to chromosome 14: der(14;21). The infant has classic Down syndrome features. The CORRECT karyotype notation is:
Correct. Translocation Down syndrome karyotype: 46 chromosomes (NOT 47), with one chromosome 14 carrying attached chromosome 21 material. Standard ISCN notation is 46,XY,rob(14;21)(q10;q10),+21.
Free trisomy 21: 47,XX,+21 or 47,XY,+21. Translocation Down syndrome: 46 chromosomes, with rob(14;21) appended. Learning both notations is essential for interpreting karyotype reports (PE29.2).
47,XY,+21 is free trisomy 21. Translocation Down syndrome has 46 chromosomes; the extra chromosome 21 material is attached to chromosome 14. ISCN: 46,XY,rob(14;21)(q10;q10),+21.
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A 6-year-old girl with Down syndrome is found to have hypothyroidism on routine screening. Thyroid-stimulating hormone (TSH) is 18 mIU/L (normal <5) and free T4 is low. What is the recommended management?
Correct. Children with Down syndrome have a higher prevalence of autoimmune thyroiditis and congenital hypothyroidism. When TSH is elevated and free T4 is low, levothyroxine replacement is indicated immediately.
Down syndrome comorbidities: AVSD, hypothyroidism (screen annually from birth), duodenal atresia, ALL, atlantoaxial instability, celiac disease, hearing loss. Annual TSH is standard of care.
Overt hypothyroidism (elevated TSH + low free T4) requires immediate levothyroxine treatment. Down syndrome guidelines recommend annual TSH screening from birth; treatment prevents further cognitive impact.
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