Down Syndrome
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Direct answer
Trisomy 21 remains the commonest surviving chromosomal disorder, roughly one in 800 to one in 1000 live births with a risk that climbs steeply after maternal age 35, produced by meiotic nondisjunction in about 95 per cent of cases, a Robertsonian translocation in 3-4 per cent and mosaicism in 1-2 per cent. The hypotonic newborn with upslanting palpebral fissures, epicanthic folds, a flat nasal bridge, single palmar crease and sandal gap needs an echocardiogram in the first month because 40-50 per cent carry congenital heart disease, most characteristically an atrioventricular septal defect. Karyotyping confirms the diagnosis and, by distinguishing nondisjunction from translocation, determines the genetic counselling: a parental 21;21 balanced translocation carrier will transmit Down syndrome to every child.
What you must remember
- Cytogenetics: nondisjunction 95 per cent (recurrence about 1 per cent plus maternal-age risk), Robertsonian translocation 3-4 per cent (usually 14;21; parental carrier testing essential), mosaic 1-2 per cent (often milder phenotype); 21;21 translocation carriers have 100 per cent affected offspring.
- Phenotype checklist: hypotonia (often the presenting neonatal sign), upslanting palpebral fissures, epicanthic folds, Brushfield spots on the iris, flat facial profile, protruding tongue, single palmar crease, clinodactyly of the fifth finger, sandal gap, excess nuchal skin.
- Cardiac: congenital heart disease in 40-50 per cent — atrioventricular septal defect (endocardial cushion defect) is the most characteristic; order echocardiography by four to six weeks even without a murmur, since murmurs may be absent in the first weeks.
- Gastrointestinal associations: duodenal atresia (antenatal double-bubble sign, bilious vomiting day one to two), Hirschsprung disease, oesophageal atresia; Down syndrome plus polyhydramnios on antenatal scan should trigger a bowel-obstruction alert.
- Antenatal screening numbers: first-trimester combined test — increased nuchal translucency with low PAPP-A and high free beta-hCG; second-trimester quadruple test — low AFP, low unconjugated oestriol, high hCG, high inhibin A.
- Haematology: transient abnormal myelopoiesis of the newborn (self-limiting blast proliferation) and a raised risk of acute lymphoblastic leukaemia in childhood; neonatal polycythaemia also occurs.
- Long-term surveillance: yearly thyroid function (hypothyroidism common), hearing and vision checks, coeliac serology if growth falters, and atlantoaxial instability — lateral neck X-ray in flexion-extension before contact sports or Special Olympics participation; screen for symptoms like neck pain or gait change earlier if present.
- Outcome: mild to moderate intellectual disability with strong social strengths; early intervention, inclusive schooling and treatment of the associated conditions, not the karyotype, determine adult function.
A typical exam case
A term newborn, small for dates, feeds poorly and lies frog-legged; the nurse notes "odd facies" and a single crease across both palms. Sequence the workup. Confirm clinically, then send a karyotype — not merely for diagnosis but for counselling: if it shows 46,XX/47,XX,+21 mosaicism the parents' recurrence risk is near baseline, while a 46,XX,rob(21;21) finding obliges parental karyotyping and a different conversation altogether. Examine the heart and schedule echocardiography within weeks even if the baby is pink and feeding; an undiagnosed atrioventricular septal defect can present with irreversible pulmonary vascular disease in the second semester. Review the abdomen for duodenal atresia if there is bilious vomiting, check a CBC for transient abnormal myelopoiesis, register the baby for thyroid screening, and refer for early stimulation. Plot growth on Down-specific charts, test vision and hearing annually, and counsel about atlantoaxial precautions before school sports.
Where students slip
Marks bleed on three details. First, the heart lesion: students write ventricular septal defect as "most common" — in trisomy 21 the characteristic and most-tested answer is atrioventricular septal defect. Second, recurrence arithmetic: nondisjunction recurrence is about 1 per cent, but a 21;21 translocation carrier transmits the syndrome in 100 per cent of conceptions; a 14;21 balanced carrier has a theoretical 10-15 per cent (maternal) recurrence, so the counselling hinges on the parental karyotype the question mentions in one clause. Third, blasts in a well newborn with Down syndrome are usually transient abnormal myelopoiesis that resolves, not leukaemia needing chemotherapy.
Frequently asked questions
Which cardiac lesion is most characteristic of Down syndrome?
Atrioventricular septal defect (endocardial cushion defect); overall congenital heart disease affects 40-50 per cent, so echocardiography is indicated in the first weeks regardless of murmur.
What is the recurrence risk in nondisjunction versus translocation Down syndrome?
Nondisjunction recurs in about 1 per cent of future pregnancies (plus maternal-age risk), whereas translocation risk depends on parental carrier status — up to 100 per cent if a parent carries a 21;21 Robertsonian translocation.
What does the second-trimester quadruple screen show in an affected fetus?
Low alpha-fetoprotein, low unconjugated oestriol, elevated hCG and elevated inhibin A; the first-trimester combined test shows thickened nuchal translucency, low PAPP-A and high free beta-hCG.
Why is atlantoaxial instability clinically important?
Laxity of the transverse ligament at C1-C2 can produce cervical cord compression during flexion injuries or contact sports; symptomatic children need surgical opinion, and asymptomatic participants are screened before Special Olympics.
What haematological conditions are associated?
Transient abnormal myelopoiesis in the neonate (usually self-resolving) and an increased lifetime risk of acute lymphoblastic and acute megakaryoblastic leukaemia.