Paediatrics chapters
Down syndrome
The commonest chromosomal syndrome: the three karyotype types, maternal age and recurrence risk, the newborn features, heart, gut, thyroid and blood problems, screening in pregnancy, and lifelong follow-up.
- Down syndrome is the commonest chromosomal syndrome (about 1 in 700-1000 births); about 92% is trisomy 21 from maternal nondisjunction (risk rises with maternal age), about 5% robertsonian translocation (usually 14;21) and 1-3% mosaic.
- Newborn: hypotonia, flat face and occiput, upslanting eyes, epicanthic folds, protruding tongue, single palmar crease, sandal gap, Brushfield spots; intellectual disability in all.
- Look for heart disease (about half; AV canal defect), duodenal atresia, hypothyroidism, leukaemia (transient myeloproliferative disorder at birth), atlantoaxial instability, hearing loss and cataract; karyotype confirms; translocation needs parental karyotypes.
On this page
Overview
Down syndrome (trisomy 21) is the commonest chromosomal disorder and the commonest autosomal trisomy compatible with life. It causes a recognisable face, hypotonia, intellectual disability, and a set of medical problems that need planned screening. Akbar quotes about 1 in 700 live births and Nelson about 1 in 1000. Most fetuses with trisomy 21 miscarry; Nelson puts fetal loss near 80%.
Cytogenetic types
| Type | Frequency | Karyotype | Key points |
|---|---|---|---|
| Trisomy 21 (nondisjunction) | About 92% | 47,XX,+21 or 47,XY,+21 | Extra chromosome from the mother in about 80% (Akbar); Nelson: nondisjunction in maternal meiosis I in 68%; rises with maternal age |
| Robertsonian translocation | About 4.5-5% | 46 chromosomes, e.g. 46,XX,t(14q21q) | Extra 21q attached to another acrocentric chromosome, most often 14; may be inherited from a balanced carrier parent |
| Mosaicism | About 1-3% | 47,+21/46 | Error after fertilisation; often milder, but findings vary widely |
A child with translocation Down syndrome has 46 chromosomes, not 47. The total count is normal because the extra 21 is fused to another chromosome.
In translocation Down syndrome, both parents must be karyotyped. About two-thirds arise new, and about one-third have a parent with a balanced translocation.
Maternal age and risk
| Mother's age | Approximate risk (Akbar) |
|---|---|
| All ages | 1 in 650 |
| 30 years | 1 in 1000 |
| 35 years | 1 in 350 |
| 40 years | 1 in 100 |
| 45 years | 1 in 50 |
Risk climbs steeply after 35 years, but Nelson advises that every pregnant woman be counselled about her own risk and offered screening, whatever her age.
Clinical features
At birth
Babies usually have normal birth weight and length and are diagnosed in the newborn period.
| Area | Features |
|---|---|
| Tone | Generalised hypotonia (most consistent sign); poor feeding, lax joints |
| Head | Small, brachycephalic with flat occiput; fontanelles close late; redundant skin at the back of the neck |
| Face | Flat face and nasal bridge, hypoplastic midface, upslanting palpebral fissures, epicanthic folds, small low-set ears |
| Mouth | Small mouth with protruding, large-looking tongue; delayed and irregular teeth |
| Eyes | Brushfield spots (white speckles around the iris edge), lens opacities, cataract |
| Hands | Short broad hands, clinodactyly (short incurved fifth finger), single transverse palmar crease (bilateral in about half), single crease on the fifth finger |
| Feet | Wide gap between first and second toes (sandal gap) with a deep crease between them |
| Skin and hair | Mottled skin (cutis marmorata), fine sparse hair |
A single palmar crease is not diagnostic: a one-sided crease is found in about 2-5% of normal babies (Akbar). Look for the whole pattern.
Development
- Intellectual disability in all; Akbar gives final IQ range of about 20-75, average near 50.
- Children are often affectionate and good-humoured.
- Puberty is delayed; males are usually infertile, females are usually fertile.
Associated problems
Heart (about 40-60%)
- Atrioventricular canal (endocardial cushion / AV septal) defect: the classic and commonest lesion.
- VSD, ASD, PDA, and tetralogy of Fallot.
- ECG in AV canal defects shows extreme left axis deviation.
- Because about half are affected, heart disease should be looked for (echocardiography) in every affected newborn.
Down syndrome = endocardial cushion defect; Turner = coarctation; Noonan = pulmonary stenosis.
Gut
- Duodenal atresia (double-bubble sign on X-ray): about one-third of babies with duodenal atresia have Down syndrome.
- Annular pancreas, imperforate anus, oesophageal atresia with tracheo-oesophageal fistula, Hirschsprung disease.
- Coeliac disease is commoner.
Endocrine
- Congenital hypothyroidism is commoner than in other babies (picked up by newborn screening).
- Acquired hypothyroidism is even more common, so thyroid function is checked periodically for life.
Blood
| Problem | Comment |
|---|---|
| Polycythaemia at birth | Haematocrit often over 70%; may need treatment |
| Transient myeloproliferative disorder (leukaemoid reaction) | High white count with blasts in the newborn; looks like leukaemia but settles within the first month; carries a later leukaemia risk |
| Leukaemia | About 10-20 times commoner (Akbar: 20 times); under 2 years: acute megakaryoblastic leukaemia; older children: ALL |
| Prolonged physiological jaundice | In the newborn |
Other problems
- Atlantoaxial instability in about 10%: risk of spinal cord injury.
- Infections more frequent; conductive hearing loss from middle ear disease.
- Obstructive sleep apnoea.
- Umbilical hernia; cataract.
- Alzheimer-like dementia in many adults over 35 years.
The transient myeloproliferative disorder of the newborn with Down syndrome is not true leukaemia and usually resolves with supportive care, but these children need follow-up because their later leukaemia risk is high.
Diagnosis
After birth
- Karyotype (blood lymphocytes) confirms the diagnosis and the type; essential for counselling because recurrence risk depends on it.
In pregnancy
| Test | Timing | Finding in Down syndrome |
|---|---|---|
| Nuchal translucency (ultrasound) | First trimester | Increased fluid behind the neck |
| First-trimester serum (PAPP-A, beta-hCG) | First trimester | With NT, detects close to 90% (Nelson) |
| Triple test | Second trimester | Low AFP, low unconjugated oestriol, high hCG |
| Quadruple test | Second trimester | Triple test plus inhibin A; detects about 80% versus about 70% for the triple test, each with about 5% false positives |
| Fetal DNA in maternal blood | Pregnancy | Non-invasive test |
| CVS or amniocentesis | First or second trimester | Fetal karyotype: the confirmatory test |
Down's triple test is "two down, one up": AFP and oestriol low, hCG high.
All serum and ultrasound tests are screening only; a high-risk result needs CVS or amniocentesis for diagnosis.
Recurrence risk and counselling
| Child's karyotype | Parents | Recurrence risk |
|---|---|---|
| Trisomy 21 | Normal | About 1% added to the maternal age risk (after 40, the age risk alone is used) |
| Mosaic | Normal | About 1% |
| Translocation, new | Normal | Low, only slightly raised |
| Translocation, mother a carrier | Balanced carrier | About 10-15% |
| Translocation, father a carrier | Balanced carrier | About 2-5% |
| 21;21 translocation in a parent | Carrier | 100% |
For a woman who has had a previous baby with Down syndrome and is now early in pregnancy, chorionic villus sampling (first trimester) or amniocentesis gives a definitive karyotype.
Management
There is no cure; care is aimed at early detection and treatment of associated problems, and support for the family.
- Newborn: karyotype; look for heart disease, gut obstruction and feeding difficulty; newborn thyroid screen; blood count for polycythaemia and the transient myeloproliferative disorder.
- Heart: drugs such as digoxin for heart failure, and cardiac surgery for significant defects.
- Infections: treat promptly with antibiotics.
- Follow-up: regular thyroid tests, hearing and eye checks, growth and development; remember atlantoaxial instability and the raised leukaemia risk.
- Family: support for the parents, genetic counselling and family planning advice.
Expect: nondisjunction as the commonest mechanism and its link with maternal age; translocation (14;21) with 46 chromosomes and the need to karyotype parents; recurrence risk of about 1% after trisomy and higher with a carrier mother; hypotonia as the main newborn sign; facial and hand features (upslanting eyes, epicanthic folds, single palmar crease, sandal gap, Brushfield spots); AV canal defect as the classic heart lesion; duodenal atresia and Hirschsprung disease; hypothyroidism needing lifelong checks; transient myeloproliferative disorder, AMKL and ALL; atlantoaxial instability; triple test pattern and CVS or amniocentesis for confirmation.
Quick revision
- Commonest chromosomal syndrome; about 1 in 700-1000 births.
- 92% trisomy (maternal nondisjunction), about 5% translocation (14;21), 1-3% mosaic.
- Risk rises with maternal age: 1 in 350 at 35, 1 in 100 at 40.
- Hypotonia, flat face and occiput, upslanting eyes, epicanthic folds, single palmar crease, sandal gap.
- Heart disease in about half: AV canal defect classic.
- Duodenal atresia, Hirschsprung disease, imperforate anus, coeliac disease.
- Hypothyroidism (congenital and acquired): check thyroid regularly.
- Transient myeloproliferative disorder at birth; leukaemia 10-20 times commoner.
- Atlantoaxial instability, hearing loss, cataract, early dementia.
- Recurrence: 1% after trisomy; karyotype parents after translocation.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why must a baby with Down syndrome have a karyotype if the diagnosis is clinically obvious?
The karyotype shows whether the cause is trisomy, translocation or mosaicism. This decides the recurrence risk and whether the parents need their own chromosomes checked.
Is Down syndrome only a problem of older mothers?
No. The risk rises with maternal age, but it is present at every age (about 1 in 1000 at 30). Screening and individual risk counselling are offered to all pregnant women.
Which heart lesion is most typical of Down syndrome?
The atrioventricular canal (endocardial cushion) defect. VSD, ASD, PDA and tetralogy of Fallot also occur, so every affected newborn needs an echocardiogram.
Why do children with Down syndrome need regular thyroid tests?
Both congenital and acquired hypothyroidism are commoner than in other children. Its features can be missed against the background of the syndrome, so blood tests are repeated throughout life.