Down Syndrome
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Direct answer
Down syndrome results from a third copy of chromosome 21 — free trisomy in about 95 per cent of cases, Robertsonian translocation in 3-4 per cent (recurrence risk relevant, parental karyotype needed) and mosaicism in 1-2 per cent — with an incidence of roughly one in 700-1000 rising with maternal age. The gestalt is set at birth: hypotonia, flat facial profile, upslanting fissures, epicanthic folds, single palmar crease, sandal gap and Brushfield spots. The diagnosis is clinical then cytogenetic, the complications drive management — congenital heart disease (atrioventricular septal defect the classic), duodenal atresia, Hirschsprung disease, hypothyroidism, hearing and vision defects, atlantoaxial instability and a raised risk of leukaemia — and structured surveillance with early intervention converts a grim old narrative into near-normal life expectancy.
What you must remember
- Genetics: free trisomy 21 (meiotic nondisjunction, maternal age-related, 95 per cent), translocation t(14;21) or t(21;21) (3-4 per cent — parental karyotype mandatory, 21;21 carriers are rare), and mosaicism (1-2 per cent, milder phenotype).
- Recurrence risk to quote: about 1 per cent (or maternal-age risk, whichever is higher) after a free trisomy, but up to 100 per cent in theoretical 21;21 translocation carriers and 10-15 per cent if the mother carries t(14;21).
- Neonatal clues: hypotonia with poor Moro is often the first sign; single palmar crease, clinodactyly, sandal gap, Brushfield spots, flat nasal bridge, macroglossia, excess nuchal skin.
- Cardiac: 40-50 per cent have congenital heart disease; atrioventricular septal defect is the characteristic lesion, with ventricular and atrial septal defects, tetralogy and patent ductus also occurring — every infant needs echocardiography in the first month.
- Gastrointestinal: duodenal atresia (the double-bubble antenatal finding) and Hirschsprung disease are the classic associations; annular pancreas and imperforate anus also occur.
- Endocrine and immune: hypothyroidism (screen at birth then annually), increased infections, and leukaemia risk about 10-20 fold — transient abnormal myelopoiesis in the neonate, megakaryoblastic leukaemia later.
- Surveillance calendar: neonatal echo and karyotype; annual thyroid function; periodic hearing and vision checks; cervical spine assessment for atlantoaxial instability before anaesthesia.
- Development and counselling: global developmental delay with intellectual disability typically in the mild-moderate range; early intervention, speech and physiotherapy, mainstream schooling with support where possible — the family needs the diagnosis communicated positively, with written resources.
How to work through it
A term infant born to a 36-year-old has hypotonia, a flat profile and a single palmar crease noticed by the intern. The neonatal sequence: confirm clinical suspicion but do not rely on the gestalt alone — order the karyotype, which will also detect translocation and change genetic counselling for the next pregnancy. Before discharge, get the echocardiogram: a murmurless atrioventricular septal defect still exists, and a failing one discovered at four months with pulmonary vascular disease is the tragedy this pathway exists to prevent. Review the newborn thyroid screen, arrange the hearing screen, check the stool pattern for Hirschsprung clues, and book the family into early intervention with the surveillance calendar in writing.
The antenatal mirror carries the other half of the exam: a 38-year-old at 12 weeks. First-trimester combined screening (nuchal translucency plus beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A), quadruple testing if she presents late, and cell-free fetal DNA as a high-sensitivity screen — with diagnostic chorionic villus sampling or amniocentesis when screening is positive, since counselling needs the karyotype, not the risk score.
How the exam frames it
Discriminators examiners test rather than just list-making: single palmar crease occurs in a small percentage of normal infants, so it is a clue, not a diagnosis; the atrioventricular septal defect association (with the "atrioventricular canal" terminology) is more testable than the generic "congenital heart disease"; and the leukaemia link runs two ways — transient abnormal myelopoiesis in the neonate that resolves spontaneously, and megakaryoblastic acute myeloid leukaemia in the preschooler. Programme linkage in India: the Rashtriya Bal Swasthya Karyakram screens newborns for birth defects including Down syndrome and congenital heart disease, feeding into free surgery schemes, while the PC-PNDT context is the ethical companion — advanced maternal age counselling and lawful prenatal screening sit against misuse of testing for sex selection, a recurring viva discussion point.
Frequently asked questions
Which karyotype finding changes recurrence counselling?
A Robertsonian translocation — parental karyotyping is mandatory, as a carrier mother of t(14;21) faces a 10-15 per cent recurrence risk versus about 1 per cent after free trisomy.
Which congenital heart lesion is characteristic of Down syndrome?
Atrioventricular septal defect (endocardial cushion defect), though ventricular septal defect, atrial septal defect and tetralogy also occur — echocardiography is universal in the first month.
Why is duodenal atresia linked with Down syndrome?
The double-bubble sign on antenatal or postnatal imaging occurs in a meaningful minority of trisomy 21 fetuses, warranting karyotype in any case of duodenal atresia.
What is transient abnormal myelopoiesis?
A spontaneous-resolving neonatal leukaemoid reaction unique to Down syndrome with blasts in the blood, resolving without therapy in most, though it marks later leukaemia risk.
Which surveillance is needed before anaesthesia in a child with Down syndrome?
Cervical spine assessment for atlantoaxial instability — neurological screening and imaging where indicated, because asymptomatic instability can precipitate cord injury.