Edward Syndrome (trisomy 18)
Edward syndrome is a severe chromosomal disorder caused by an extra copy of chromosome 18, typically presenting at birth with characteristic features including clenched fists with overlapping fingers, rocker-bottom feet, cardiac defects, and profound developmental disability, with most affected infants dying within the first year of life.
Edward Syndrome (Trisomy 18) — Paediatric Clinical Notes
Edward syndrome is a chromosomal disorder caused by the presence of an extra copy (whole or partial) of chromosome 18 [1][2]. The name comes from John H. Edwards, who first described the syndrome in 1960.
- "Trisomy" → Greek: "tri" = three, "soma" = body → three copies of a chromosome instead of the normal two.
- Chromosome 18 is one of the smaller autosomes, but it carries ~300 genes, many critical for embryonic development, cardiac morphogenesis, and neurological formation.
- It is classified as a lethal chromosomal abnormality — the majority of prenatally diagnosed cases die in utero, and among live births, 50% die within the first 2 weeks of life; only 5–10% survive the first year [2].
Key Concept
Edward syndrome is the second most common autosomal trisomy observed in live births (after Down syndrome / Trisomy 21). Despite being "common" among trisomies, it is almost universally fatal — this distinguishes its prognostic counselling dramatically from Trisomy 21.
2. Epidemiology
- Incidence: approximately 1 in 3,000 live births [1], though some sources cite 1 in 5,000–8,000 due to differing inclusion of stillbirths. Felix Lai's notes quote 1 in 15,000 births [2] — this lower figure may reflect only confirmed live births surviving to postnatal assessment. The discrepancy arises because a substantial proportion are lost prenatally.
- The conception incidence is much higher (~1 in 2,500 pregnancies) because most affected embryos are spontaneously aborted.
- Incidence increases with advanced maternal age (same mechanism as Trisomy 21).
- Female predominance: M:F ≈ 1:3 to 1:4 [1][2].
- The reason for this is not fully understood [1], but proposed explanations include:
- Preferential in utero loss of affected males — male fetuses with Trisomy 18 may have a higher spontaneous abortion rate.
- Possible protective effect of a second X chromosome in females (speculative).
| Timepoint | Survival |
|---|---|
| Prenatal detection → live birth | ~50% die in utero |
| First 2 weeks of life | ~50% of live births die |
| First year | Only 5–10% survive [2] |
| Median survival (live births) | ~14 days [1] |
- Extended survival is possible [1], particularly in mosaic Trisomy 18 or with aggressive supportive care, but the vast majority have profound disability.
3. Risk Factors
- The primary risk factor is advanced maternal age, just as with Trisomy 21 [2].
- Why? During oogenesis, primary oocytes are arrested in prophase I of meiosis from fetal life. Over decades, the prolonged meiotic arrest leads to:
- Degradation of cohesin proteins holding sister chromatids together.
- Loss of chiasma maintenance.
- Increased risk of non-disjunction — failure of paired chromosomes (or sister chromatids) to separate properly during meiosis I or II.
- The extra chromosome 18 typically arises from maternal meiosis I non-disjunction (~60%) or maternal meiosis II non-disjunction (~30%).
- If a parent carries a balanced translocation involving chromosome 18, the recurrence risk depends on the specific translocation and which parent carries it.
Understanding why an extra chromosome 18 causes such devastating effects requires understanding what genes reside on it:
| Region | Key Genes / Loci | Relevance |
|---|---|---|
| 18q | TGIF (TG-interacting factor) | Involved in holoprosencephaly pathway |
| 18q | BCL2 | Anti-apoptotic oncogene — overexpression disrupts normal programmed cell death during organogenesis |
| 18q | MC4R | Melanocortin receptor — involved in growth regulation |
| 18p | Various developmental genes | Brain and craniofacial development |
- The gene dosage imbalance (3 copies instead of 2 → ~150% normal gene product) disrupts tightly regulated developmental pathways. This is why trisomies of larger chromosomes (with more genes) are almost always lethal, while trisomies of smaller chromosomes (13, 18, 21) or sex chromosomes are the only ones compatible with live birth.
Why Are Only Trisomies 13, 18, 21 (and Sex Chromosomes) Seen in Live Births?
Chromosomes 13, 18, and 21 are relatively gene-poor compared to other autosomes. The gene dosage imbalance from having 3 copies is therefore "less catastrophic" — though still usually lethal for T13 and T18. Trisomy of gene-rich chromosomes (e.g., chromosome 1) causes such severe developmental disruption that the embryo fails very early and is spontaneously aborted before clinical recognition.
5. Aetiology and Pathophysiology
5.1 Genetic Mechanisms
Three genetic mechanisms produce Edward syndrome [2]:
- 90% are caused by meiotic non-disjunction [2].
- Non-disjunction: during meiosis (usually maternal meiosis I), the two copies of chromosome 18 fail to separate. One gamete receives 2 copies, the other receives 0. Fertilisation of the gamete with 2 copies by a normal sperm → zygote with 3 copies (trisomy).
- Associated with advanced maternal age [2].
- All cells in the body carry 47 chromosomes → most severe phenotype.
- Presence of 3 copies of chromosome 18 in some cells and 2 copies in others [2].
- Caused by mitotic non-disjunction or translocation error after fertilisation [2] — i.e., the initial zygote is normal (46 chromosomes), but during early mitotic divisions, one cell line loses or gains a chromosome 18.
- Phenotype is extremely variable, ranging from apparently normal to similar to complete trisomy [2].
- The severity depends on:
- Proportion of trisomic cells.
- Distribution — which tissues/organs contain the trisomic cells.
- Timing of the mitotic error — earlier errors → more cells affected → more severe.
- Partial trisomy 18 may result from a balanced translocation or inversion carried by 1 parent [2].
- Only a segment of chromosome 18 is present in triplicate — phenotype depends on which genes are duplicated.
- Critical region: the long arm of chromosome 18 (18q11→18q12) is thought to contain the "critical region" responsible for the classic phenotype.
- Important: if a parent carries a balanced translocation, recurrence risk is significantly higher than sporadic full trisomy → parental karyotyping is essential.
The extra chromosome 18 causes gene dosage imbalance → overexpression of chromosome 18 genes → disruption of:
- Cardiac morphogenesis → congenital heart defects (virtually 100%)
- CNS development → microcephaly, cerebellar hypoplasia, intellectual disability
- Musculoskeletal patterning → clenched fists, rocker-bottom feet, short sternum
- Renal development → horseshoe kidney, hydronephrosis
- Craniofacial development → micrognathia, low-set ears, prominent occiput
- Growth → severe intrauterine growth restriction (IUGR)
The BCL2 gene on 18q21 (anti-apoptosis) is overexpressed → dysregulated apoptosis during organogenesis → aberrant structural development.
| Type | Karyotype | Proportion | Mechanism | Phenotype Severity |
|---|---|---|---|---|
| Full Trisomy 18 | 47, XX+18 or 47, XY+18 | ~94% | Meiotic non-disjunction | Severe (classic) |
| Mosaic Trisomy 18 | 47, +18 / 46 | ~5% | Post-zygotic mitotic error | Variable (mild → severe) |
| Partial Trisomy 18 | Various translocations | ~1% | Parental balanced translocation/inversion | Depends on duplicated segment |
Exam Pearl
When you encounter a child with features "suggestive" of Trisomy 18 but milder presentation or longer survival than expected, think mosaic Trisomy 18. The phenotype can range from apparently normal to full-blown Edward syndrome.
7. Clinical Features
The clinical features of Edward syndrome are extensive and affect virtually every organ system. The hallmark is a combination of IUGR + characteristic hand posture (clenched fists with overlapping fingers) + cardiac malformations + distinctive craniofacial features.
| Symptom | Pathophysiological Basis |
|---|---|
| Low birth weight (>90% of cases) [1] | Severe IUGR due to placental insufficiency + impaired fetal growth from gene dosage imbalance affecting growth factors |
| Poor feeding / feeding difficulties | Micrognathia (small jaw) → difficulty latching; CNS impairment → poor suck-swallow coordination; oesophageal atresia (in some) |
| Weak cry | CNS involvement — cerebellar hypoplasia, generalised hypotonia progressing to hypertonia |
| Failure to thrive | Combination of cardiac failure (high-output demands from CHD), feeding difficulties, and intrinsic growth impairment |
| Respiratory distress | Congenital heart disease (pulmonary overcirculation from VSD), diaphragmatic eventration, or central apnoea from CNS malformation |
| Seizures | Structural brain abnormalities → abnormal cortical excitability |
| Apnoeic episodes | Central apnoea from brainstem/cerebellar malformation |
7.2 Signs (What You Find on Examination)
| Sign | Pathophysiological Basis |
|---|---|
| Microcephaly [1] | Impaired brain growth — gene dosage imbalance disrupts neuronal proliferation and migration |
| Prominent occiput (dolichocephaly) [1] | Abnormal calvarial bone growth — elongated skull shape due to disproportionate cranial bone development (premature closure or abnormal growth of certain sutures) |
| Short neck [1] | Defective cervical vertebral and soft tissue development |
| Dysplastic / malformed ears [1] | Abnormal first and second branchial arch development → low-set, posteriorly rotated, with pointed helices ("fawn-like" ears) |
| Small mouth and chin (micrognathia) [1] | Mandibular hypoplasia from first branchial arch developmental defect |
| Narrow palpebral fissures | Periorbital tissue underdevelopment |
| Epicanthic folds | Midface hypoplasia |
Distinguishing the Occiput
In Trisomy 18: the occiput is prominent (the back of the head "sticks out"). In Trisomy 21: the occiput is flat (brachycephaly). This is a classic differentiating exam point.
| Sign | Pathophysiological Basis |
|---|---|
| Flexed, overlapping fingers / clenched hands (95%) [1] | Characteristic hand posture: 2nd finger overlaps 3rd, 5th overlaps 4th — due to abnormal muscle tone and joint/tendon development from chromosome 18 gene dosage effects on connective tissue and neuromuscular patterning |
| Rocker-bottom feet with prominent heels (90%) [1] | Abnormal tarsal bone development → convex sole with prominent calcaneus; "rocker-bottom" = the foot looks like the bottom of a rocking chair |
| Short, prominent sternum and widely spaced nipples [1] | Short sternum (due to abnormal sternal ossification centre development) → shield-like chest configuration |
| Hypoplastic nails | Distal limb growth impairment |
| Limited hip abduction | Abnormal acetabular development |
| Radial aplasia / hypoplasia (occasionally) | Limb bud patterning defect |
Classic Hand Posture in Trisomy 18:
Index finger (2nd) overlaps middle finger (3rd)
Little finger (5th) overlaps ring finger (4th)
Fists are tightly clenched
This is virtually PATHOGNOMONIC and present in ~95% of cases.High Yield — The Clenched Fist
The clenched fist with overlapping fingers is the single most recognisable and frequently tested physical sign of Trisomy 18. Remember the pattern: 2nd over 3rd, 5th over 4th. In contrast, a single transverse palmar crease is associated with Trisomy 21 and Trisomy 13.
Cardiac defects are present in virtually 100% of cases [1].
| Cardiac Defect | Frequency | Pathophysiological Basis |
|---|---|---|
| Ventricular Septal Defect (VSD) | Most common (94%) [1] | Failure of interventricular septum to close during cardiac morphogenesis (weeks 4–8); gene dosage imbalance disrupts endocardial cushion development |
| Myxomatous change of valves | Common [1] | Abnormal extracellular matrix deposition in valve leaflets → thickened, redundant, incompetent valves (polyvalvular disease) |
| Atrial Septal Defect (ASD) | Common | Incomplete atrial septum formation |
| Patent Ductus Arteriosus (PDA) | Common | Failure of DA closure mechanisms |
| Coarctation of Aorta (CoA) | Less common | Abnormal aortic arch development |
| Double-outlet right ventricle | Occasional | Conal septal malalignment |
Why is cardiac involvement so severe and universal? Chromosome 18 genes are critically involved in cardiac neural crest cell migration and endocardial cushion formation. The 150% gene dosage disrupts the precise temporal and spatial signalling required for cardiac septation → almost all patients have structural heart disease.
Polyvalvular disease (myxomatous change of valves) is relatively specific to Trisomy 18 — it is less commonly seen in other trisomies and can be a clue on fetal echocardiography.
| Feature | Pathophysiological Basis |
|---|---|
| Cerebellar hypoplasia (most common, 32%) [1] | Chromosome 18 genes involved in cerebellar granule cell proliferation → insufficient development |
| Severe intellectual disability | Global cortical developmental impairment |
| Hypotonia (initially) → hypertonia | Evolving tone abnormalities due to upper motor neuron pathway dysfunction |
| Seizures | Abnormal cortical architecture → epileptogenicity |
| Apnoea | Central apnoea from brainstem immaturity/malformation |
| Feature | Pathophysiological Basis |
|---|---|
| Renal anomalies [1] | Horseshoe kidney, hydronephrosis, ectopic kidney, renal agenesis — due to disrupted metanephric development |
| Feature | Notes |
|---|---|
| Single umbilical artery | Normally 2 arteries + 1 vein; SUA associated with multiple congenital anomalies |
| Omphalocele / diaphragmatic hernia | Midline closure defects from abnormal body wall development |
| Cryptorchidism (in males) | Impaired testicular descent |
| Cleft lip/palate (occasional) | Midface developmental disruption |
- Oesophageal atresia (OA) — Trisomy 18 is one of the chromosomal disorders associated with the VACTERL association and oesophageal atresia [3]. This is clinically important because:
- If a neonate presents with OA, chromosomal analysis should be performed.
- The presence of T18 significantly worsens the prognosis of OA repair.
VACTERL Association and Trisomy 18
While VACTERL association and Trisomy 18 can both feature oesophageal atresia/tracheo-oesophageal fistula, cardiac anomalies, and renal/vertebral anomalies, they are distinct entities. However, 50–70% of oesophageal atresia cases are associated with VACTERL, T13/T18/T21, or CHARGE syndrome [3]. Always check karyotype in a neonate with OA.
| System | Key Features | Frequency |
|---|---|---|
| Growth | Low birth weight, IUGR | > 90% |
| Craniofacial | Microcephaly, prominent occiput, dysplastic ears, micrognathia | > 90% |
| Hands | Clenched fists with overlapping fingers | 95% |
| Feet | Rocker-bottom feet | 90% |
| Chest | Short sternum, widely spaced nipples | Common |
| Cardiac | VSD (94%), polyvalvular disease | ~100% |
| Neurological | Cerebellar hypoplasia, intellectual disability, seizures | > 80% |
| Renal | Horseshoe kidney, hydronephrosis | ~60% |
| GI | OA/TOF, omphalocele, malrotation | ~15–30% |
| GU | Cryptorchidism | Common in males |
8. Growth and Development Considerations
- Almost all infants with Trisomy 18 demonstrate severe IUGR with birth weight often < 2,500g even at term.
- Postnatal growth is severely impaired — specific Trisomy 18 growth charts exist but are rarely used given the poor prognosis.
- Profound global developmental delay in all survivors.
- Milestones are severely delayed or never achieved.
- Even in mosaic cases with milder phenotype, significant intellectual disability is expected.
9. Family-Centred Care and Communication
When Trisomy 18 is diagnosed prenatally (via NIPT, amniocentesis, or CVS):
- Non-directive counselling — present factual information about prognosis, quality of life, and options.
- Options include:
- Continuation of pregnancy with comfort care at birth.
- Continuation with limited intervention plan.
- Termination of pregnancy (where legal and acceptable to the family).
- In Hong Kong, termination is legally available up to 24 weeks' gestation for severe fetal abnormality.
- Goals of care discussions are essential — the family must be involved in decisions about:
- Resuscitation at birth.
- Level of intervention (e.g., cardiac surgery, ventilation).
- Comfort/palliative care.
- There is increasing recognition that some families choose intervention — centres in Japan and some Western centres report improved survival with cardiac surgery and full intervention, though quality of life remains a concern.
- All decisions are made by parents/legal guardians in the neonatal period.
- The paediatric team should involve clinical ethics and palliative care teams when there is disagreement about goals of care.
- Most die prenatally or in infancy [1].
- Median survival: 14 days [1].
- Only 5% reach 1 year [1].
- Extended survival is possible [1], particularly with:
- Mosaic Trisomy 18.
- Full intervention including cardiac surgery.
- Children surviving past 1 year can occasionally survive into teens/adulthood with profound disability.
- Low recurrence risk (for full trisomy cases) [1], except in Robertsonian translocation or balanced translocation carriers [1].
- In Hong Kong, the universal antenatal screening programme includes:
- First-trimester combined screening (maternal age + nuchal translucency + serum markers) — can detect T18.
- Non-invasive prenatal testing (NIPT) using cell-free fetal DNA — increasingly used as first-line or second-tier screening; very high sensitivity and specificity for T18 (> 95% detection rate, very low false positive rate).
- Confirmatory testing by amniocentesis or chorionic villus sampling (CVS) with karyotype or chromosomal microarray.
- The Hospital Authority provides genetic counselling services through the Clinical Genetics Service at Queen Mary Hospital and other tertiary centres.
- Given the small but significant proportion caused by parental translocation, parental karyotyping should be offered after any confirmed case of Trisomy 18.
High Yield Summary
Edward Syndrome (Trisomy 18) — Pre-DDx/Dx/Mx Summary
- Definition: Extra chromosome 18 → lethal chromosomal abnormality
- Epidemiology: 2nd most common autosomal trisomy; 1/3,000–1/15,000 live births; F > M (4:1); increases with maternal age
- Genetics: ~94% full trisomy (meiotic non-disjunction), ~5% mosaic (mitotic error), ~1% translocation (familial risk)
- Cardinal clinical features:
- Microcephaly with prominent occiput
- Clenched fists with overlapping fingers (2nd over 3rd, 5th over 4th) — 95%
- Rocker-bottom feet — 90%
- Cardiac defects in ~100%, most commonly VSD (94%) and polyvalvular myxomatous disease
- Low birth weight (> 90%)
- Cerebellar hypoplasia (most common CNS anomaly)
- Prognosis: Median survival = 14 days; only 5% survive to 1 year
- Recurrence: Low, unless parental balanced translocation → always offer parental karyotyping
- Distinguish from T21: Prominent occiput (T18) vs flat occiput (T21); clenched fists (T18) vs single palmar crease (T21)
- Distinguish from T13: T13 classical triad = microphthalmos + cleft lip/palate + polydactyly
Active Recall — Edward Syndrome (Trisomy 18): Definition to Clinical Features
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 505–506) [2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p. 838) [3] Senior notes: Maksim Surgery Notes.pdf (p. 331) — Oesophageal atresia and VACTERL/T18 association [4] Lecture slides: Block C - The malformed child: hereditary syndromes and anomalies.pdf [5] Lecture slides: GC 151. The malformed child hereditary syndromes and anomalies.pdf [6] Senior notes: Ryan Ho Opthalmology.pdf (p. 122) — Congenital cataract associations including Edward syndrome
Differential Diagnosis of Edward Syndrome (Trisomy 18)
Edward syndrome presents with a constellation of features — IUGR, craniofacial dysmorphism, limb anomalies, and cardiac defects — that overlap with several other chromosomal, syndromic, and non-chromosomal conditions. In clinical practice, the differential arises in two main scenarios:
- Antenatally: Ultrasound findings (IUGR, cardiac defect, clenched fists, choroid plexus cysts) raise suspicion — the DDx is other causes of multiple congenital anomalies detected on screening.
- Postnatally: A dysmorphic neonate with multiple anomalies — the DDx is other genetic syndromes that share overlapping features before karyotype results return.
The key principle: No single feature is pathognomonic in isolation. It is the pattern recognition — the specific combination of features — that narrows the diagnosis. Confirmation always requires cytogenetic analysis (karyotype, FISH, or chromosomal microarray).
| Condition | Overlapping Features with T18 | Distinguishing Features | Cardiac Defect Pattern |
|---|---|---|---|
| Patau syndrome (Trisomy 13) [1] | Microcephaly, dysplastic ears, low birth weight, cardiac defects, renal anomalies, lethal prognosis | Classical triad: microphthalmos + cleft lip/palate + postaxial polydactyly; scalp defects; holoprosencephaly (HPE); single palmar crease | ASD, TOF, TGA (NOT VSD predominant) [1] |
| Down syndrome (Trisomy 21) [1] | Cardiac defects, low birth weight possible, hypotonia, dysplastic ears | Flat occiput (vs prominent in T18); upslanting palpebral fissures; protruding tongue; single palmar crease; sandal gap; hypotonia (vs hypertonia in T18); much better prognosis | AVSD (most characteristic), VSD [7] |
| Turner syndrome (45,X) [1] | Short stature, widely spaced nipples, webbed neck, cardiac defects, renal anomalies | Only females; lymphoedema at birth (not clenched fists); cubitus valgus; short 4th metacarpal; ovarian dysgenesis; normal intelligence | Left-sided lesions: CoA, bicuspid AV [1][8] |
| Noonan syndrome [8] | Short stature, widely spaced nipples, webbed neck, cardiac defects, low-set ears, dysmorphic facies | Autosomal dominant (RAS-MAPK pathway); downslanting palpebral fissures; ptosis; cryptorchidism; normal karyotype; hypertelorism | Right-sided lesions: pulmonary valve stenosis, HCM [8] |
| DiGeorge syndrome (22q11.2 deletion) [8][9] | Cardiac defects, micrognathia, low-set ears, feeding difficulties | CATCH-22 mnemonic: Cardiac (conotruncal), Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia; no clenched fists or rocker-bottom feet | Conotruncal: interrupted aortic arch, truncus arteriosus, TOF [8][9] |
| Smith-Lemli-Opitz syndrome | IUGR, microcephaly, micrognathia, cardiac defects, renal anomalies, 2-3 toe syndactyly | Autosomal recessive (7-dehydrocholesterol reductase deficiency); 2-3 toe syndactyly (pathognomonic); ambiguous genitalia in males; low cholesterol levels; no overlapping fingers | VSD, ASD, AVSD |
| Pena-Shokeir syndrome (Fetal Akinesia Sequence) | IUGR, clenched hands/camptodactyly, rocker-bottom feet, pulmonary hypoplasia | Polyhydramnios + fetal akinesia; multiple joint contractures (arthrogryposis); lung hypoplasia is the cause of death (not cardiac); no specific cardiac defect pattern | Variable |
| Distal arthrogryposis syndromes | Clenched fists, overlapping fingers, camptodactyly | Contractures but no cardiac defects, no IUGR, no craniofacial features; normal karyotype; familial (AD); preserved intellect | None typically |
| Fetal alcohol spectrum disorder (FASD) | IUGR, microcephaly, cardiac defects (VSD), micrognathia | Maternal alcohol exposure history; smooth philtrum; thin vermillion border; short palpebral fissures; no clenched fists or rocker-bottom feet | VSD, ASD |
| CHARGE syndrome | Cardiac defects, ear anomalies, IUGR, feeding difficulties | CHD7 gene mutation; Coloboma; Heart defects; Atresia choanae; Retardation of growth; Genital anomalies; Ear anomalies; cranial nerve dysfunction | TOF, AV canal, aortic arch anomalies |
Systematic Approach to DDx by Presenting Feature
The clenched fist with overlapping fingers is highly suggestive of T18 but the DDx includes:
- Pena-Shokeir syndrome (fetal akinesia) — arthrogryposis is generalised, hands are in a "frog-like" posture, lung hypoplasia dominates
- Distal arthrogryposis — isolated hand/foot contractures, no systemic features
- Restrictive dermopathy — tight shiny skin, arthrogryposis, lethal
- Trisomy 18 — confirmed by the combination with prominent occiput + VSD + rocker-bottom feet
| Differential | Key distinguishing antenatal USS finding |
|---|---|
| Trisomy 18 | Clenched fists, single umbilical artery, choroid plexus cysts, strawberry-shaped skull, polyhydramnios |
| Trisomy 13 | Holoprosencephaly, polydactyly, midline facial clefting |
| Trisomy 21 | Nuchal thickening, absent/hypoplastic nasal bone, echogenic bowel, duodenal atresia ("double bubble") |
| Turner syndrome | Cystic hygroma, hydrops fetalis, coarctation |
| Triploidy (69,XXX/XXY) | Very severe asymmetric IUGR, large cystic placenta (partial mole) |
VSD is the most common congenital heart defect overall and is seen in many syndromes. The associated dysmorphic features guide the DDx:
| VSD + ... | Think of... |
|---|---|
| VSD + prominent occiput + clenched fists + rocker-bottom feet | Trisomy 18 |
| VSD + flat occiput + upslanting eyes + single palmar crease | Trisomy 21 |
| VSD + polydactyly + cleft lip + microphthalmos | Trisomy 13 |
| VSD + elfin facies + hypercalcaemia | Williams syndrome (though supravalvular AS more characteristic) |
| VSD + absent thymus + hypocalcaemia | DiGeorge syndrome |
Trisomy 18 vs Trisomy 13 vs Trisomy 21 — Exam Classic
| Feature | Trisomy 18 (Edward) | Trisomy 13 (Patau) | Trisomy 21 (Down) |
|---|---|---|---|
| Occiput | Prominent | Sloping forehead | Flat (brachycephaly) |
| Hands | Clenched, overlapping fingers | Single palmar crease, polydactyly | Single palmar crease, clinodactyly |
| Feet | Rocker-bottom | Rocker-bottom possible | Sandal gap |
| Eyes | Narrow palpebral fissures | Microphthalmos, coloboma | Upslanting, Brushfield spots |
| Mouth | Micrognathia | Cleft lip ± palate | Protruding tongue |
| Scalp | Normal | Scalp defects (aplasia cutis) | Normal |
| Brain | Cerebellar hypoplasia | Holoprosencephaly | Generally normal structure |
| Cardiac | VSD (94%), polyvalvular disease | ASD, TOF, TGA | AVSD (most characteristic), VSD |
| Most common CHD | VSD [1] | ASD [1] | AVSD [7] |
| Survival | Median 14 days | Similar to T18 | Median ~60 years |
| F:M ratio | 4:1 (F > M) | Equal | 1:1 |
Common Exam Trap
Students often confuse the cardiac defect patterns between the three autosomal trisomies. Remember:
- T18 → VSD (94%) + polyvalvular disease
- T13 → ASD, TOF, TGA
- T21 → AVSD (most characteristic / "classic") + VSD
Also, rocker-bottom feet can occur in both T18 and T13, but the clenched fist with overlapping fingers is highly specific to T18 [1][7].
Conditions Associated with Overlapping Features — Expanded Discussion
- Incidence: 1/8,000 live births [1].
- Why it overlaps: same category (autosomal trisomy), same mechanism (non-disjunction), similarly lethal.
- Classical triad: microphthalmos + cleft lip/palate + polydactyly (postaxial) [1].
- Key differentiators: scalp defects (aplasia cutis congenita), holoprosencephaly (midline brain fusion failure — can range from alobar HPE to mild form), microphthalmia/cyclopia in severe cases [1][7].
- Prognosis: same as Edward syndrome [1] — median survival ~7–10 days, < 10% survive 1 year.
- Most common autosomal trisomy and most common genetic cause of intellectual disability [1].
- Incidence: ~1/600–800 live births [1].
- Key differentiators from T18:
- Hypotonia (T21) vs hypertonia (T18)
- Flat occiput / brachycephaly (T21) vs prominent occiput (T18)
- Good prognosis (T21, life expectancy ~60y) vs lethal (T18)
- GI associations in T21: duodenal atresia, Hirschsprung disease [7]
- Only females affected (monosomy X).
- Overlaps with T18 in: widely spaced nipples, short neck, cardiac defects, renal anomalies.
- Key differentiators: lymphoedema at birth (puffy hands/feet — not clenched), cystic hygroma on antenatal scan, short stature (SHOX gene haploinsufficiency), ovarian dysgenesis, normal to near-normal intelligence [1].
- Cardiac lesions are left-sided: bicuspid aortic valve, coarctation [1][8].
- Autosomal dominant (RAS-MAPK pathway mutations — PTPN11 most common).
- Phenotypically resembles Turner but normal karyotype, affects both sexes.
- Key differentiators: downslanting (not upslanting) palpebral fissures, ptosis, pulmonary stenosis with dysplastic valve (right-sided lesions) [8], bleeding diathesis.
- No clenched fists or rocker-bottom feet.
- Microdeletion on chromosome 22 — most common microdeletion syndrome.
- Mnemonic: CATCH-22 — Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia; chromosome 22 [9].
- Cardiac defects are conotruncal: interrupted aortic arch (type B), truncus arteriosus, TOF [8][9].
- Key differentiators from T18: presence of hypocalcaemia (hypoparathyroidism), immunodeficiency (T-cell deficit from thymic hypoplasia), no limb anomalies typical of T18.
- When an omphalocele is detected (a feature that can occur in T18), the DDx includes:
- Trisomy 18 — omphalocele + cardiac defect + clenched fists + IUGR
- Beckwith-Wiedemann syndrome — omphalocele + macrosomia (opposite of IUGR!) + macroglossia + ear creases; associated with hepatoblastoma [10]
- Isolated omphalocele — no syndromic features
- The distinction is critical because omphalocele in T18 has a much worse prognosis than in Beckwith-Wiedemann or isolated cases [10].
- Edward syndrome (Trisomy 18) is listed as an associated syndrome for hepatoblastoma [10], along with Beckwith-Wiedemann, FAP, Down syndrome, and Li-Fraumeni.
- This is a rare but testable association.
Once clinical suspicion arises, the DDx is resolved by cytogenetic/molecular testing:
| Test | What It Detects | Turnaround |
|---|---|---|
| Rapid FISH | Aneuploidy for chromosomes 13, 18, 21, X, Y | 24–48 hours |
| Karyotype | Full chromosomal complement; translocations, mosaicism | 7–14 days |
| Chromosomal Microarray (CMA) | Copy number variants including microdeletions (e.g., 22q11.2) | 2–4 weeks |
| NIPT (antenatal) | Cell-free fetal DNA screening for T13/T18/T21 | 5–10 days |
When to Suspect Trisomy 18 Over Other DDx
The combination of prominent occiput + clenched fists with overlapping fingers (2nd over 3rd, 5th over 4th) + rocker-bottom feet + VSD is virtually diagnostic pending karyotype confirmation. No other common condition produces this exact constellation.
Active Recall — Differential Diagnosis of Trisomy 18
References
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 503–506) [7] Senior notes: Maksim Paediatric Notes.pdf (p. 204) [8] Senior notes: Ryan Ho Cardiology.pdf (p. 185) — Syndromes associated with congenital heart diseases [9] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p. 581) — DiGeorge syndrome / CATCH-22 [10] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p. 1077) — Hepatoblastoma associations including T18; Maksim Surgery Notes.pdf (p. 333) — Omphalocele associations
Diagnostic Criteria, Algorithm, and Investigations for Edward Syndrome (Trisomy 18)
1. Diagnostic Criteria
There are no formal "diagnostic criteria" for Trisomy 18 in the way that, say, rheumatic fever has the Jones criteria. The diagnosis is ultimately cytogenetic — you need to demonstrate the extra chromosome 18 in the laboratory. However, the clinical pathway has two phases: clinical suspicion (pattern recognition) and cytogenetic confirmation.
Clinical suspicion is raised when a neonate (or fetus on antenatal scan) demonstrates the characteristic pattern of anomalies:
Postnatal clinical suspicion — presence of ≥3 of the following in combination should trigger urgent karyotype:
| Cardinal Feature | Approximate Frequency |
|---|---|
| Low birth weight / IUGR | > 90% [1] |
| Microcephaly with prominent occiput | > 90% [1] |
| Clenched fists with overlapping fingers (2nd over 3rd, 5th over 4th) | 95% [1] |
| Rocker-bottom feet with prominent heels | 90% [1] |
| Congenital heart defect (especially VSD ± polyvalvular disease) | ~100% [1] |
| Dysplastic/malformed ears | > 80% [1] |
| Micrognathia (small mouth and chin) | > 80% [1] |
| Short sternum with widely spaced nipples | Common [1] |
Antenatal suspicion — ultrasound findings that should prompt further investigation:
| Antenatal USS Finding | Notes |
|---|---|
| IUGR (especially early and symmetrical) | Non-specific but raises suspicion in combination |
| Choroid plexus cysts | Present in ~1% of normal fetuses — only significant when combined with other markers |
| Clenched fists / overlapping fingers | Highly suggestive when persistent |
| Single umbilical artery | Associated with chromosomal abnormalities |
| Cardiac defect (especially VSD) | Prompts fetal karyotyping |
| Strawberry-shaped skull (prominent occiput) | Characteristic cranial shape |
| Rocker-bottom feet | Highly suggestive |
| Omphalocele | Consider T18 in DDx of omphalocele |
| Polyhydramnios | Due to impaired fetal swallowing |
Key Principle — Clinical vs Cytogenetic Diagnosis
Clinical features raise suspicion; cytogenetic analysis confirms the diagnosis. You cannot diagnose Trisomy 18 on clinical features alone — there is always overlap with other syndromes. The definitive diagnosis requires demonstration of an extra chromosome 18 (or its material) by karyotype, FISH, or chromosomal microarray (CMA) [2].
The diagnosis is confirmed when one of the following is demonstrated:
| Karyotype Finding | Type | Clinical Correlation |
|---|---|---|
| 47, XX+18 or 47, XY+18 | Full Trisomy 18 | Classic phenotype; ~94% of cases; caused by meiotic non-disjunction [2] |
| 47, +18 / 46 (mixed cell lines) | Mosaic Trisomy 18 | Variable phenotype; ~5%; caused by post-zygotic mitotic error [2] |
| Partial duplication of 18q material via translocation | Partial Trisomy 18 | Phenotype depends on segment; ~1%; may result from balanced translocation carried by parent [2] |
2. Diagnostic Algorithm
The algorithm depends on whether the diagnosis is being pursued antenatally or postnatally.
The antenatal detection pathway in Hong Kong follows the standard screening cascade:
-
First-trimester combined screening (11–13+6 weeks):
- Maternal age
- Nuchal translucency (NT) measurement — increased NT in T18
- Maternal serum markers: PAPP-A (low) + free β-hCG (low)
- In T18, both PAPP-A and free β-hCG are low — this is distinct from T21 where β-hCG is high
-
Non-invasive prenatal testing (NIPT) — cell-free fetal DNA from maternal blood:
- Increasingly used as first-line or second-tier screening in Hong Kong
- Detection rate for T18 > 95%, with very low false positive rate (~0.1%)
- NIPT is a screening test, NOT diagnostic — positive results require confirmatory invasive testing
-
Invasive confirmatory testing (offered when screening is positive):
- Chorionic villus sampling (CVS) — performed at 11–14 weeks; provides placental cells for karyotype/CMA
- Amniocentesis — performed at ≥15 weeks; provides fetal cells from amniotic fluid
- Both carry ~0.1–0.5% miscarriage risk
-
Second-trimester anomaly scan (18–22 weeks):
- May detect structural anomalies (cardiac defects, clenched fists, rocker-bottom feet, choroid plexus cysts) even if first-trimester screening was normal or declined
NIPT Serum Markers — T18 vs T21
In Trisomy 18: both PAPP-A and free β-hCG are LOW ("everything is low — the baby is failing"). In Trisomy 21: PAPP-A is LOW but free β-hCG is HIGH. This distinction is frequently tested. The mnemonic: T18 = "All Down" (both markers down); T21 = "One Up, One Down" (β-hCG up, PAPP-A down).
When a neonate is born with features suggestive of Trisomy 18:
- Clinical assessment — full dysmorphology examination by the paediatric team
- Urgent FISH — sent from peripheral blood for rapid result (24–48 hours)
- Full karyotype — from peripheral blood lymphocytes (7–14 days turnaround)
- Chromosomal microarray (CMA) — if karyotype is normal but clinical suspicion persists (detects submicroscopic duplications/deletions)
- Concurrent investigations to delineate associated anomalies:
- Echocardiography (cardiac defects)
- Renal ultrasound (renal anomalies)
- Cranial ultrasound (cerebellar hypoplasia, other CNS malformations)
- Ophthalmological assessment
3. Investigation Modalities — Key Findings and Interpretations
| Investigation | Specimen | Key Finding in T18 | Turnaround | Interpretation Notes |
|---|---|---|---|---|
| Rapid FISH | Peripheral blood / amniotic fluid / CVS | 3 signals for chromosome 18 probe (normally 2) | 24–48 hours | Rapid preliminary confirmation; does NOT detect translocations or mosaicism reliably |
| G-banded karyotype | Peripheral blood lymphocytes / amniotic fluid / CVS | 47, XX+18 or 47, XY+18 (full trisomy); or 47, +18 / 46 (mosaic); or structural rearrangement (translocation) | 7–14 days | Gold standard for full chromosomal analysis; identifies type (full vs mosaic vs translocation); counts 20+ metaphases to assess mosaicism |
| Chromosomal microarray (CMA) | Blood / tissue | Copy number gain of entire chromosome 18 or partial segment | 2–4 weeks | Detects submicroscopic gains/losses not visible on karyotype; particularly useful for partial trisomy or when karyotype is unexpectedly normal; cannot detect balanced translocations |
| NIPT (antenatal) | Maternal blood | Increased representation of chromosome 18 sequences in cell-free DNA | 5–10 days | Screening test only — sensitivity > 95%, specificity > 99.5%, but positive predictive value depends on prior probability (maternal age, prevalence); must be confirmed by invasive testing |
| Parental karyotyping | Parental blood | Balanced translocation involving chromosome 18 in one parent | 7–14 days | Essential when translocation Trisomy 18 is identified — determines recurrence risk for future pregnancies; if parental karyotypes are normal, translocation arose de novo (low recurrence risk) [2] |
Why Is FISH Not Enough?
FISH gives a rapid answer (24–48h) by counting fluorescent signals for chromosome 18, but it cannot distinguish full trisomy from translocation, and it may miss low-level mosaicism. A full G-banded karyotype examining ≥20 metaphases is required to:
- Confirm the type (full vs mosaic vs translocation).
- Guide recurrence risk counselling.
- Determine if parental karyotyping is needed. Always send both FISH (for speed) AND karyotype (for completeness).
| Marker | Normal Function | Finding in T18 | Compare with T21 |
|---|---|---|---|
| PAPP-A (Pregnancy-Associated Plasma Protein A) | Protease that releases IGF from binding proteins → promotes placental/fetal growth | Low — impaired placental function | Low |
| Free β-hCG | Subunit of hCG maintaining corpus luteum and placental function | Low — impaired trophoblast function | High |
| Nuchal translucency (NT) | USS measurement of fluid at fetal neck (11–13+6 weeks) | Increased — lymphatic drainage dysfunction, cardiac failure | Increased |
Why are both markers low in T18? The trisomic placenta is severely dysfunctional in T18 — both trophoblast-derived hCG production and PAPP-A secretion are impaired, reflecting the global developmental failure. In T21, the placenta is relatively better preserved (β-hCG is actually overproduced due to immature trophoblast proliferation).
If performed (less common now with NIPT available):
| Marker | Finding in T18 |
|---|---|
| AFP (alpha-fetoprotein) | Low |
| uE3 (unconjugated oestriol) | Low |
| hCG | Low |
| Inhibin A | Low |
In T18, all four markers tend to be low — again reflecting global placental dysfunction. This is sometimes called the "all-low" pattern.
| Timing | USS Finding | Significance |
|---|---|---|
| First trimester | Increased nuchal translucency | Non-specific marker of chromosomal abnormality; due to impaired lymphatic drainage or cardiac dysfunction |
| First trimester | Abnormal ductus venosus flow | Reflects early cardiac dysfunction |
| Second trimester | Choroid plexus cysts | Found in ~1% of normal fetuses; in isolation, low predictive value; in combination with other markers, increases T18 suspicion |
| Second trimester | Clenched fists / overlapping fingers | Highly suggestive when persistent |
| Second trimester | Strawberry-shaped cranium (prominent occiput + narrow bifrontal diameter) | Characteristic cranial shape of T18 |
| Second trimester | Cardiac defect (VSD) | Present in virtually all T18 fetuses; may be first finding prompting karyotype |
| Second trimester | Rocker-bottom feet | Convex sole visible on sagittal foot view |
| Second trimester | Single umbilical artery | Normal = 2 arteries + 1 vein; SUA associated with chromosomal abnormalities |
| Second trimester | Omphalocele | Midline abdominal wall defect with herniated viscera covered by membrane |
| Second trimester | IUGR | Symmetrical early-onset growth restriction |
| Second trimester | Polyhydramnios | Impaired fetal swallowing due to CNS dysfunction or oesophageal atresia |
| Second trimester | Renal anomalies (horseshoe kidney, hydronephrosis) | Abnormal metanephric development |
Choroid Plexus Cysts — A Common Exam Discussion Point
Isolated choroid plexus cysts (CPCs) on second-trimester USS are common and usually benign (~1% of normal pregnancies). They only become significant when combined with other markers of T18. Current guidance: isolated CPCs in a low-risk patient with normal anatomy and normal first-trimester screening do NOT require amniocentesis. However, CPCs + any additional structural anomaly or abnormal screening → offer invasive testing.
Once T18 is confirmed (or strongly suspected), the following investigations are performed to guide management decisions:
| Investigation | What It Assesses | Expected Findings in T18 |
|---|---|---|
| Echocardiography | Cardiac anatomy and function | VSD (94%) [1]; polyvalvular myxomatous disease; ASD; PDA; may have complex defects |
| Renal ultrasound | Renal anatomy | Horseshoe kidney; hydronephrosis; renal agenesis; ectopic kidney |
| Cranial ultrasound | Brain structure (through open fontanelle) | Cerebellar hypoplasia (32%) [1]; other structural brain anomalies; ventriculomegaly |
| Ophthalmological examination | Eye anomalies | Congenital cataract (T18 is a recognised syndromal cause of congenital cataract [6]); corneal opacity; microphthalmos (less common than T13) |
| Skeletal survey (if indicated) | Bony anomalies | Short sternum; radial aplasia; vertebral anomalies |
| Abdominal USS | GI anomalies | Omphalocele; malrotation |
| Hearing assessment | Sensorineural / conductive hearing loss | May have hearing impairment due to ear dysplasia |
| Investigation | Purpose |
|---|---|
| Parental karyotyping | To identify balanced translocation carrier status; essential when translocation Trisomy 18 is found [2]; determines recurrence risk |
| Genetic counselling referral | Explanation of diagnosis, prognosis, recurrence risk, and reproductive options for future pregnancies |
| Scenario | Interpretation | Next Step |
|---|---|---|
| NIPT positive for T18 | Screening test only — not diagnostic | Offer CVS or amniocentesis for confirmatory karyotype |
| FISH shows 3 signals for chr 18 | Preliminary confirmation of trisomy | Await full karyotype for type classification |
| Karyotype: 47, XX+18 | Full Trisomy 18 confirmed | Goals of care discussion; concurrent organ assessment; genetic counselling |
| Karyotype: 47, +18 / 46 | Mosaic Trisomy 18 | Prognosis more variable; extent of mosaicism guides counselling; may need tissue karyotype (e.g., skin fibroblasts) |
| Karyotype: 46 chromosomes but with translocation involving chr 18 | Partial Trisomy 18 | Parental karyotyping essential [2]; higher recurrence risk if parent is carrier |
| Karyotype normal but clinical features suggestive | Consider alternative diagnosis | Send CMA; consider other DDx (Pena-Shokeir, distal arthrogryposis, etc.) |
Tissue Karyotype in Suspected Mosaicism
If blood karyotype is normal but clinical suspicion remains high, mosaicism may be confined to certain tissues. A skin fibroblast karyotype can detect tissue-confined mosaicism that blood lymphocyte karyotype misses. This is particularly relevant in suspected mosaic Trisomy 18 with a milder phenotype.
High Yield Summary — Diagnosis of Trisomy 18
- Clinical suspicion: Pattern of prominent occiput + clenched fists (2nd over 3rd, 5th over 4th) + rocker-bottom feet + VSD + IUGR
- Antenatal screening: NIPT (> 95% detection rate); first-trimester combined screening (both PAPP-A and free β-hCG are LOW in T18)
- Antenatal confirmation: CVS (11–14 weeks) or amniocentesis (≥15 weeks) → karyotype/CMA
- Postnatal confirmation: Urgent FISH (24–48h) + full G-banded karyotype (7–14 days) from peripheral blood
- Concurrent organ assessment: Echocardiography (VSD ~94%), renal USS, cranial USS, ophthalmology
- Parental karyotyping: Essential when translocation type identified — determines recurrence risk
- Three types: Full trisomy (94%) vs mosaic (5%) vs translocation (1%) — karyotype distinguishes them
Active Recall — Diagnosis of Trisomy 18
References
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 505–506) [2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p. 838) [6] Senior notes: Ryan Ho Opthalmology.pdf (p. 122) — Congenital cataract syndromal associations including Edward syndrome
Management of Edward Syndrome (Trisomy 18)
Before discussing specific interventions, it is essential to understand the fundamental management principle for Trisomy 18:
There is no cure for Trisomy 18 [7]. Management is supportive, focused on regular screening for potential comorbidities, specific treatment (drug, surgery, transplantation where appropriate), and genetic counselling [7].
The management of Trisomy 18 is unique in paediatrics because it sits at the intersection of medical ethics, family-centred care, and palliative medicine. The decisions made are profoundly influenced by:
- The lethal nature of the condition — median survival 14 days, only 5% survive to 1 year [1][2].
- The values and wishes of the family.
- The evolving (and somewhat controversial) debate about whether aggressive intervention prolongs meaningful life or prolongs suffering.
There are broadly two management paradigms that exist on a spectrum:
| Approach | Philosophy | Practice |
|---|---|---|
| Comfort / palliative care (traditional) | T18 is a lethal condition; aggressive intervention prolongs dying, not living | Warmth, feeding support, family bonding; no ventilation or cardiac surgery; focus on quality of life |
| Individualised intervention (emerging, e.g., Japan, some Western centres) | Some children with T18 can survive with intervention; families should be offered choices | Selected cardiac surgery, ventilatory support, feeding procedures; careful case-by-case assessment |
Exam Framing — What to Say
In an HKUMed exam, the safest and most defensible approach is: "Management should be individualised and family-centred. A multidisciplinary team discussion including neonatologists, geneticists, cardiologists, and palliative care specialists should establish goals of care with the family. Both comfort care and limited intervention are valid options depending on the clinical context and family values." This avoids being dogmatically "no intervention" (outdated) or uncritically "full intervention" (controversial).
The management pathway follows a structured timeline:
- Antenatal management (when diagnosed prenatally)
- Delivery room / immediate postnatal management
- Neonatal period management (first 28 days)
- Ongoing care (for survivors beyond neonatal period)
- Genetic counselling and family support (throughout)
3. Detailed Management by Phase
| Component | Details |
|---|---|
| Genetic counselling | Non-directive counselling — explain the diagnosis (Trisomy 18), expected features, prognosis (median 14 days, 5% 1-year survival), and range of outcomes. Present options without prescribing a particular course [7] |
| Reproductive options | Termination of pregnancy — available in Hong Kong up to 24 weeks for severe fetal abnormality (Offences Against the Person Ordinance, Cap. 212). Continuation of pregnancy — with either comfort care or individualised intervention plan |
| Birth planning | If continuing, develop a detailed birth plan: delivery mode, resuscitation preferences, presence of neonatal team, who will be present, skin-to-skin contact, baptism/religious rites if desired |
| Delivery mode | Vaginal delivery is generally preferred — caesarean section is typically not performed for fetal indication alone in confirmed T18 given the lethal prognosis. However, maternal indications for caesarean still apply |
| Monitoring | Serial USS to monitor growth, amniotic fluid volume (polyhydramnios may develop), and fetal wellbeing |
Caesarean Section in Trisomy 18
A common exam discussion point: Caesarean section purely for fetal benefit is generally NOT indicated in confirmed full Trisomy 18, because the lethal prognosis means the risks of surgery to the mother are not justified by meaningful improvement in fetal outcome. This is distinct from maternal indications for caesarean (e.g., obstructed labour, placenta praevia) which remain valid.
| Component | Details | Rationale |
|---|---|---|
| Thermoregulation | Dry, wrap, skin-to-skin contact | Neonates with T18 are often IUGR/low birth weight → high surface-area-to-volume ratio → rapid heat loss |
| Airway management | Gentle suctioning if needed; positioning | Micrognathia may cause upper airway obstruction (similar principle to Pierre Robin sequence) |
| Resuscitation | Based on pre-agreed birth plan — may range from full NLS algorithm to comfort care only | The resuscitation plan should be documented antenatally if diagnosis is known. If postnatal diagnosis, initial stabilisation is reasonable while assessment occurs |
| Family bonding | Facilitate immediate skin-to-skin, family photographs, memory making | This may be the only time the family has with their child — every moment is precious |
| Rapid confirmation | Send urgent FISH from cord blood or peripheral blood | Even if antenatal diagnosis was made, postnatal confirmation is standard practice |
3.3 Supportive Care — The Foundation (All Patients)
Regardless of whether comfort care or active intervention is chosen, the following supportive measures apply:
| Intervention | Indication | Details |
|---|---|---|
| Oral feeding (breast or bottle) | If suck-swallow coordination is adequate | Many T18 infants have poor suck reflex due to CNS impairment and micrognathia; oral feeding should be attempted but may not be achievable |
| Nasogastric (NG) tube feeding | If oral feeding is inadequate but not pursuing long-term intervention | Allows enteral nutrition while preserving comfort; minimally invasive |
| Gastrostomy tube | If pursuing individualised intervention and long-term survival anticipated | Placed surgically or endoscopically; allows long-term enteral feeding; indicated in survivors with persistent feeding difficulties |
Why is feeding so difficult in T18?
- Micrognathia → small mandible → tongue falls back → difficulty latching
- CNS malformation → poor suck-swallow-breathe coordination
- Cardiac failure → increased caloric demands + fatigue during feeds → failure to thrive
- Oesophageal atresia (if present) → cannot swallow at all → surgical consideration
- For survivors, these therapies aim to:
- PT: Maintain range of motion (contractures from overlapping fingers, rocker-bottom feet); prevent skin breakdown; respiratory physiotherapy
- OT: Sensory stimulation; environmental adaptation
- ST: Oro-motor therapy to optimise feeding function
| Symptom | Management | Rationale |
|---|---|---|
| Pain/distress | Sucrose for procedural pain (neonatal); paracetamol; morphine if severe (palliative dosing) | Neonatal pain assessment tools (e.g., NIPS, PIPP-R) guide management; all infants feel pain — comfort is paramount |
| Secretions | Gentle suctioning; glycopyrrolate or hyoscine if excessive | Reduces "death rattle" and family distress; improves comfort |
| Seizures | Phenobarbital (first-line in neonates) | Structural brain anomalies → seizure risk; neonatal seizure doses: phenobarbital loading 20 mg/kg IV, maintenance 5 mg/kg/day |
| Apnoea | Positioning; caffeine (if pursuing active management) | Central apnoea from brainstem/cerebellar malformation; caffeine citrate 20 mg/kg loading, 5–10 mg/kg/day maintenance |
| Respiratory distress | Oxygen; nasal CPAP if appropriate; avoid intubation/ventilation in comfort care | Goal is comfort — supplemental oxygen relieves dyspnoea without invasive measures |
3.4 Specific Treatment: Drug, Surgery, Transplantation [7] — Active/Individualised Intervention
This section applies to families who choose active management after thorough counselling.
| Intervention | Indication | Contraindications / Considerations |
|---|---|---|
| Pulmonary artery banding (PAB) | VSD with pulmonary overcirculation and heart failure in a child selected for intervention | Less invasive palliative procedure; reduces pulmonary blood flow without full repair |
| VSD repair | Selected cases with favourable anatomy, surviving beyond neonatal period, family wishes active management | Full cardiopulmonary bypass carries significant risk in a child with multiple comorbidities |
| PDA ligation | Haemodynamically significant PDA | May be done surgically or with catheter-based devices |
| Valve surgery | Severe polyvalvular disease with haemodynamic compromise | Technically very challenging in a small neonate with myxomatous valves |
Evidence: Japanese centres have reported improved survival with cardiac surgery in selected T18 patients (1-year survival increasing from ~5% to ~25% in operated patients). However, this remains controversial — survivors still have profound disability and repeated hospitalisations.
Cardiac Surgery in Trisomy 18 — Evolving Practice
Historically, T18 was considered an absolute contraindication to cardiac surgery. This is no longer universally the case. Current consensus (2024–2026): cardiac surgery may be offered on a case-by-case basis after thorough multidisciplinary discussion and informed family consent. The decision should weigh the severity of cardiac disease, presence of other life-limiting anomalies, family values, and institutional capabilities. In Hong Kong, this would typically involve the paediatric cardiac surgery team at Queen Mary Hospital or Prince of Wales Hospital.
| Intervention | When Considered | Notes |
|---|---|---|
| Supplemental oxygen | Hypoxia from cardiac defect or central apnoea | Low-flow nasal cannula; non-invasive |
| Nasal CPAP | Obstructive or mixed apnoea | May be appropriate if pursuing active management |
| Mechanical ventilation | Generally avoided in comfort care; considered in individualised intervention | If intubated, may be very difficult to wean; ethical discussion essential before initiating |
| Tracheostomy | Rarely — only in survivors with chronic upper airway obstruction | Significant long-term care implications |
| Anomaly | Surgical Option | Consideration |
|---|---|---|
| Oesophageal atresia / TOF | Primary repair or staged repair | T18 significantly worsens the prognosis of OA repair — survival is poor even with surgery; decision depends on goals of care |
| Omphalocele | Primary closure or staged reduction; or conservative (paint and wait) | If comfort care chosen, omphalocele can be managed with topical antiseptic to allow epithelialisation without surgery |
| Renal anomalies | Usually managed conservatively | Surgical intervention rarely indicated given overall prognosis |
For survivors beyond the neonatal period:
| System | Screening | Frequency |
|---|---|---|
| Cardiac | Echocardiography | At diagnosis, then as clinically indicated |
| Growth | Weight, length, head circumference | Each visit — use T18-specific growth charts if available |
| Development | Developmental assessment | Regular — expect profound delay; guide early intervention |
| Hearing | Auditory brainstem response (ABR) or OAE | At diagnosis; repeat if concerns |
| Vision | Ophthalmological exam | At diagnosis; annual if surviving |
| Renal | Renal USS + renal function | At diagnosis; periodic monitoring |
| Orthopaedic | Assessment of contractures, scoliosis | As needed |
| Component | Details |
|---|---|
| Inheritance / sporadic → recurrence risk [7] | Full trisomy (94%): sporadic meiotic non-disjunction → low recurrence risk (~1% above age-related baseline) [1]. Translocation: parental karyotyping essential [2] — if parent is balanced translocation carrier, recurrence risk is significantly higher |
| Reproductive options [7] | Pre-implantation genetic diagnosis (PGD): IVF with embryo biopsy and selection of unaffected embryos — available in Hong Kong. Prenatal diagnosis: CVS or amniocentesis in future pregnancies. NIPT: as screening in subsequent pregnancies. Pre-conception counselling: discussion of maternal age-related risk |
| Psychosocial support | Referral to support groups (e.g., SOFT — Support Organisation for Trisomy 18, 13, and Related Disorders); bereavement counselling |
High Yield — General Management Framework for Chromosomal Disorders
The general management framework for chromosomal abnormalities [7]:
- No cure
- Supportive: PT, OT, ST
- Regular screening for potential comorbidities
- Specific treatment: drug, surgery, transplantation (where appropriate)
- Genetic counselling: inheritance/sporadic → recurrence risk; reproductive options including pre-implantation genetic diagnosis and prenatal diagnosis
This framework applies to ALL chromosomal disorders (T21, T18, T13, Turner, etc.) — learn it once, apply it universally.
Given that the majority of infants with T18 die within days to weeks, palliative care is central:
| Component | Details |
|---|---|
| Palliative care team referral | Involve early — ideally antenatally or at diagnosis |
| Symptom control | Pain, secretions, seizures, respiratory distress — as detailed above |
| Family support | Allow unlimited family access; facilitate sibling visits; provide private space |
| Memory making | Hand/footprints, photographs, lock of hair, naming ceremony, religious rites |
| Advance care planning | Document agreed goals of care; "comfort care" or "limited intervention" plan; DNAR (Do Not Attempt Resuscitation) order if appropriate and agreed with family |
| Bereavement support | Counselling; follow-up contact; support group referral; information about post-mortem examination (offer — helps confirm diagnosis and may aid future counselling) |
| Post-mortem examination | Offer to family — confirms diagnosis, identifies anomalies not detected in life, provides information for recurrence risk counselling |
Ethical Framework — Key Principles
When managing T18, the ethical principles guiding decisions are:
- Best interests of the child — the paramount consideration under Hong Kong law
- Family autonomy — parents' values and wishes are central to decision-making
- Proportionality — interventions should be proportionate to expected benefit
- Non-maleficence — avoid causing unnecessary suffering
- Shared decision-making — the medical team provides information and recommendations; the family makes the decision
In cases of disagreement between team and family, involve clinical ethics committee and consider legal advice.
| Phase | Key Actions |
|---|---|
| Antenatal | Genetic counselling; reproductive options (termination / continuation); birth plan; delivery mode (vaginal preferred); serial USS monitoring |
| Delivery room | Based on pre-agreed plan; thermoregulation; gentle airway management; family bonding; FISH for confirmation |
| Neonatal | Goals of care discussion; organ assessment (echo, renal USS, cranial USS); feeding support; symptom management; palliative care referral |
| Survivors | Supportive: PT, OT, ST [7]; regular screening for comorbidities [7]; specific treatment as appropriate [7]; developmental support |
| Genetic | Parental karyotyping if translocation [2]; genetic counselling: recurrence risk + reproductive options (PGD, prenatal diagnosis) [7] |
| End of life | Comfort care; symptom control; family support; memory making; bereavement support; offer post-mortem |
High Yield Summary — Management of Trisomy 18
- No cure [7] — management is supportive + symptomatic + genetic counselling
- General framework [7]: Supportive (PT, OT, ST) → Regular screening for comorbidities → Specific treatment (drug, surgery) → Genetic counselling (recurrence risk, PGD, prenatal diagnosis)
- Goals of care: Individualised, family-centred — spectrum from comfort care to selected intervention
- Antenatally: Non-directive counselling; termination or continuation; vaginal delivery preferred; CS not for fetal indication alone
- Cardiac surgery: No longer absolute contraindication — case-by-case decision after MDT discussion
- Feeding: Oral → NG → gastrostomy (graduated approach depending on goals)
- Palliative care: Central to management — symptom control, family bonding, memory making, bereavement support
- Genetic counselling: Low recurrence risk for full trisomy; parental karyotyping essential for translocation type; reproductive options: PGD and prenatal diagnosis [7]
Active Recall — Management of Trisomy 18
References
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 505–506) [2] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p. 838) [7] Senior notes: Maksim Paediatric Notes.pdf (pp. 202–204) — General investigation and management framework for genetic/chromosomal disorders
Complications of Edward Syndrome (Trisomy 18)
The complications of Trisomy 18 are not truly "complications" in the conventional sense (i.e., unexpected adverse events arising from a disease or its treatment). Rather, they are the inevitable consequences of the multi-system organ malformations inherent to the syndrome. Because cardiac defects are present in ~100% [1], cerebellar hypoplasia in 32% [1], and renal anomalies are common [1], the complications are predictable and progressive.
The complications can be organised into:
- Direct complications of congenital malformations (cardiac, neurological, renal, GI)
- Complications of the overall condition (growth failure, infections, death)
- Complications of treatment (iatrogenic — relevant when active intervention is pursued)
- Psychosocial and family complications
- Rare long-term complications (relevant to the small minority of survivors)
Cardiac defects are present in virtually 100% of T18 infants [1] and are the leading cause of morbidity and mortality.
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Congestive heart failure (CHF) | VSD (94%) [1] → left-to-right shunt → pulmonary overcirculation → volume overload of left heart → CHF. Additionally, myxomatous change of valves [1] → valvular regurgitation → further volume overload | Tachypnoea, tachycardia, hepatomegaly, poor feeding, diaphoresis during feeds, failure to thrive |
| Pulmonary hypertension (pHTN) | Large unrepaired VSD → chronic excessive pulmonary blood flow → shear stress damages pulmonary arterioles → progressive pulmonary vascular remodelling → irreversible pulmonary arterial hypertension | Worsening cyanosis, loud P2 on auscultation, right ventricular heave |
| Eisenmenger syndrome | End-stage of untreated large L-to-R shunt: pulmonary vascular disease → reversal of shunt → R-to-L → cyanosis [11]. Triad: congenital L-to-R shunt + pulmonary arterial disease + cyanosis | Central cyanosis, digital clubbing, loss of previously audible VSD murmur (because shunt gradient equalises), exertional dyspnoea, reactive erythrocytosis [11] |
| Infective endocarditis (IE) | Turbulent flow across structural cardiac defects → endothelial damage → bacterial seeding during transient bacteraemia | Fever, new/changing murmur, embolic phenomena — however, given the short survival, IE is uncommon |
| Arrhythmias | Structural cardiac abnormalities + myxomatous valves → abnormal conduction pathways; polyvalvular disease → chamber dilation → substrate for arrhythmia | Bradycardia, supraventricular tachycardia, heart block |
Why is CHF so common and so early? In a normal neonate, pulmonary vascular resistance (PVR) is high at birth and falls gradually over the first weeks. As PVR falls, the left-to-right shunt across the VSD increases → pulmonary overcirculation develops → CHF manifests at 4–8 weeks of life. In T18, this is the typical timeline — but the infant's overall fragility (IUGR, poor feeding, CNS impairment) means they tolerate heart failure very poorly.
Eisenmenger Syndrome in T18 — Theoretical vs Clinical
In practice, most T18 infants die before Eisenmenger syndrome develops (which typically takes months to years of unrepaired shunt). However, in the rare survivors — particularly those with mosaic T18 or those not offered cardiac repair — Eisenmenger physiology can develop. Once established, it is irreversible and contraindicates cardiac repair [11]. The only curative option at that stage is heart-lung transplantation [11], which is not offered in T18.
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Seizures | Structural brain abnormalities (cerebellar hypoplasia (32%) [1], cortical malformations) → abnormal neuronal connectivity → epileptogenicity | Neonatal seizures (subtle, tonic, clonic); recurrent seizures in survivors |
| Central apnoea | Brainstem and cerebellar malformation → impaired central respiratory drive → periodic breathing progressing to apnoeic episodes | Apnoeic episodes, desaturations, bradycardic events; often the terminal event |
| Profound intellectual disability | Global cortical developmental impairment from gene dosage imbalance → failure to achieve any developmental milestones | No purposeful interaction in severe cases; may have limited social responsiveness in milder (mosaic) cases [12] |
| Feeding incoordination | CNS dysfunction → poor suck-swallow-breathe reflex coordination | Choking, aspiration, failure to establish oral feeding |
| Aspiration pneumonia | Secondary to feeding incoordination (above) + micrognathia → pooling of secretions + gastro-oesophageal reflux | Recurrent respiratory infections, consolidation on CXR |
Why is central apnoea so important? Central apnoea is often the proximate cause of death in T18. The brainstem respiratory centres are malformed → the infant simply stops breathing. This can occur unpredictably, even in otherwise "stable" infants. Families must be counselled about this.
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Severe failure to thrive | Multi-factorial: (1) intrinsic growth impairment from gene dosage imbalance; (2) CHF → increased metabolic demands + poor intake; (3) feeding difficulties (micrognathia, poor suck); (4) malabsorption (GI anomalies) | Weight, length, and head circumference all severely below normal centiles |
| Gastro-oesophageal reflux (GOR) | Oesophageal dysmotility + hypotonia → incompetent lower oesophageal sphincter → acid reflux | Vomiting, irritability, aspiration events |
| Necrotising enterocolitis (NEC) | Premature/IUGR neonates + cardiac disease (low cardiac output → mesenteric hypoperfusion) → ischaemic bowel injury | Abdominal distension, bilious vomiting, bloody stools, pneumatosis on AXR |
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Renal failure | Renal anomalies [1] — horseshoe kidney, hydronephrosis, renal agenesis → impaired renal function | Oliguria, elevated creatinine, electrolyte derangement |
| Urinary tract infections (UTIs) | Structural renal anomalies → urinary stasis → predisposition to ascending infections | Fever, poor feeding, sepsis in neonates |
| Obstructive uropathy | Hydronephrosis / ureteropelvic junction obstruction → ureteral dilation → progressive renal damage if untreated | Palpable flank mass, recurrent UTIs |
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Recurrent respiratory infections | Poor cough reflex (CNS impairment) + aspiration + cardiac failure (pulmonary congestion) → ideal environment for bacterial colonisation | Pneumonia, bronchiolitis, respiratory failure |
| Sepsis | Overall immune immaturity (IUGR, prematurity) + invasive procedures (NG tubes, IV lines) + poor skin integrity | Neonatal sepsis, late-onset sepsis |
| Otitis media | Craniofacial anomalies (dysplastic ears, abnormal eustachian tube anatomy) → impaired middle ear drainage | Recurrent ear infections, conductive hearing loss |
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Oesophageal atresia / TOF | Developmental failure of tracheo-oesophageal separation; T18 is associated with OA/TEF [3] | Unable to swallow; drooling; "can't pass NG tube"; aspiration of secretions |
| Omphalocele complications | Midline closure defect → herniated viscera → risk of rupture, infection, bowel ischaemia [3][10] | Visible omphalocele at birth; if ruptured → exposed bowel → emergency surgical coverage |
| Malrotation with volvulus | Abnormal intestinal rotation during embryogenesis → abnormal mesenteric attachment → risk of midgut volvulus | Bilious vomiting (surgical emergency), abdominal distension |
| Feeding intolerance | GI dysmotility + GOR + structural anomalies | Vomiting, abdominal distension, poor weight gain |
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Progressive joint contractures | Abnormal muscle tone + limited movement + connective tissue abnormalities → progressive shortening of tendons and ligaments | Worsening fixed flexion deformities of fingers, wrists, hips |
| Scoliosis | Vertebral anomalies + hypotonia → abnormal spinal curvature | Visible truncal asymmetry; may worsen respiratory function |
| Skin breakdown | Poor nutrition + immobility + thin skin → pressure injuries | Pressure ulcers over bony prominences |
| Complication | Pathophysiology | Clinical Manifestation |
|---|---|---|
| Congenital cataract | Edward syndrome is a recognised syndromal cause of congenital cataract [6] — lens opacification from abnormal lens fibre development | Leukocoria (white pupil), failure of visual fixation |
| Corneal opacity | Anterior segment dysgenesis | Visible corneal clouding |
For the ~5% who survive beyond 1 year [1] (typically mosaic or partial trisomy cases):
| Complication | Details |
|---|---|
| Hepatoblastoma | Edward syndrome is a recognised association for hepatoblastoma [10] — the most common primary liver malignancy in early childhood. Although rare, screening with periodic AFP levels and abdominal USS may be considered in survivors |
| Wilms tumour | Rare association with Trisomy 18; renal anomalies may predispose |
| Chronic lung disease | From recurrent aspiration, recurrent infections, and pulmonary overcirculation |
| Chronic constipation | GI dysmotility |
| Hearing loss | Conductive (from recurrent otitis media + ear dysplasia) and/or sensorineural |
Hepatoblastoma and Trisomy 18
Edward syndrome (Trisomy 18) is listed among the associated syndromes for hepatoblastoma [10], alongside Beckwith-Wiedemann, FAP, Down syndrome, and Li-Fraumeni. This is a rare but testable association in exam settings. In survivors, clinicians should maintain a low threshold for investigating hepatomegaly or rising AFP.
When active intervention is pursued, the following iatrogenic complications may arise:
| Intervention | Potential Complications |
|---|---|
| Cardiac surgery | Perioperative mortality (very high in T18); bleeding; infection; difficulty weaning from bypass; post-operative heart failure; arrhythmias |
| Mechanical ventilation | Ventilator-associated pneumonia; air leak (pneumothorax); difficulty weaning → chronic ventilator dependence; tracheal injury |
| Gastrostomy | Wound infection; tube displacement; GOR worsening; aspiration |
| OA/TOF repair | Anastomotic leak; stricture; recurrent TOF; GOR; tracheomalacia |
| Omphalocele repair | Abdominal compartment syndrome (from ↑ intra-abdominal pressure) → difficult ventilation, ↓venous return, ↓urine output [3] |
These are often underappreciated but are critical in family-centred paediatric care:
| Complication | Details |
|---|---|
| Parental grief and bereavement | Anticipatory grief (antenatal diagnosis); complicated grief after death; feelings of guilt, anger, isolation |
| Sibling impact | Siblings may feel neglected, confused, or frightened; age-appropriate communication is essential |
| Relationship strain | Disagreements between parents about goals of care; financial stress from hospital stays |
| Decision-making burden | Parents may experience lasting distress about decisions made (whether to intervene or not); ongoing support is essential |
| Mental health | Parental depression, anxiety, post-traumatic stress disorder (PTSD); screen and refer |
| Impact on future reproductive decisions | Anxiety about future pregnancies; need for ongoing genetic counselling and reassurance about recurrence risk |
Understanding the proximate causes of death is important for counselling families:
| Cause | Mechanism | Frequency |
|---|---|---|
| Central apnoea | Brainstem/cerebellar malformation → cessation of respiratory drive | Most common |
| Cardiac failure | Progressive CHF from unrepaired VSD + valvular disease | Very common |
| Respiratory failure | Aspiration pneumonia, pulmonary overcirculation, pulmonary hypoplasia | Common |
| Sepsis | Secondary to aspiration, UTI, or line-related infection | Common |
| Multiorgan failure | Cumulative effect of cardiac, renal, and CNS dysfunction | Terminal pathway |
High Yield Summary — Complications of Trisomy 18
- Leading cause of death: Central apnoea (brainstem malformation) and cardiac failure (VSD + polyvalvular disease)
- Cardiac: CHF → pulmonary hypertension → Eisenmenger (if survives long enough); arrhythmias; IE (rare)
- Neurological: Seizures, central apnoea, profound intellectual disability, feeding incoordination → aspiration
- Growth: Severe failure to thrive (multi-factorial: cardiac, feeding, intrinsic growth impairment)
- Renal: Renal failure from structural anomalies; recurrent UTIs
- GI: OA/TOF; omphalocele complications; malrotation/volvulus; GOR → aspiration
- Infectious: Recurrent respiratory infections, sepsis, otitis media
- Ophthalmological: Congenital cataract [6]
- Rare/long-term: Hepatoblastoma [10] (testable association); Wilms tumour; chronic lung disease
- Iatrogenic: Post-surgical complications (cardiac, GI)
- Psychosocial: Parental grief, sibling impact, decision-making burden, mental health
- Prognosis: median survival 14 days; only 5% reach 1 year [1]
Active Recall — Complications of Trisomy 18
References
[1] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 505–506) [3] Senior notes: Maksim Surgery Notes.pdf (pp. 331, 333) — Oesophageal atresia, omphalocele, and associated conditions [6] Senior notes: Ryan Ho Opthalmology.pdf (p. 122) — Congenital cataract syndromal associations including Edward syndrome [10] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p. 1077) — Hepatoblastoma associations including Trisomy 18 [11] Senior notes: Ryan Ho Cardiology.pdf (p. 186) — Eisenmenger syndrome [12] Senior notes: Ryan Ho Psychiatry.pdf (p. 244) — Intellectual disability and Trisomy 18
High Yield Summary
Edward Syndrome (Trisomy 18) — Pre-DDx/Dx/Mx Summary
- Definition: Extra chromosome 18 → lethal chromosomal abnormality
- Epidemiology: 2nd most common autosomal trisomy; 1/3,000–1/15,000 live births; F > M (4:1); increases with maternal age
- Genetics: ~94% full trisomy (meiotic non-disjunction), ~5% mosaic (mitotic error), ~1% translocation (familial risk)
- Cardinal clinical features:
- Microcephaly with prominent occiput
- Clenched fists with overlapping fingers (2nd over 3rd, 5th over 4th) — 95%
- Rocker-bottom feet — 90%
- Cardiac defects in ~100%, most commonly VSD (94%) and polyvalvular myxomatous disease
- Low birth weight (> 90%)
- Cerebellar hypoplasia (most common CNS anomaly)
- Prognosis: Median survival = 14 days; only 5% survive to 1 year
- Recurrence: Low, unless parental balanced translocation → always offer parental karyotyping
- Distinguish from T21: Prominent occiput (T18) vs flat occiput (T21); clenched fists (T18) vs single palmar crease (T21)
- Distinguish from T13: T13 classical triad = microphthalmos + cleft lip/palate + polydactyly
High Yield Summary — Diagnosis of Trisomy 18
- Clinical suspicion: Pattern of prominent occiput + clenched fists (2nd over 3rd, 5th over 4th) + rocker-bottom feet + VSD + IUGR
- Antenatal screening: NIPT (> 95% detection rate); first-trimester combined screening (both PAPP-A and free β-hCG are LOW in T18)
- Antenatal confirmation: CVS (11–14 weeks) or amniocentesis (≥15 weeks) → karyotype/CMA
- Postnatal confirmation: Urgent FISH (24–48h) + full G-banded karyotype (7–14 days) from peripheral blood
- Concurrent organ assessment: Echocardiography (VSD ~94%), renal USS, cranial USS, ophthalmology
- Parental karyotyping: Essential when translocation type identified — determines recurrence risk
- Three types: Full trisomy (94%) vs mosaic (5%) vs translocation (1%) — karyotype distinguishes them
High Yield Summary — Management of Trisomy 18
- No cure [7] — management is supportive + symptomatic + genetic counselling
- General framework [7]: Supportive (PT, OT, ST) → Regular screening for comorbidities → Specific treatment (drug, surgery) → Genetic counselling (recurrence risk, PGD, prenatal diagnosis)
- Goals of care: Individualised, family-centred — spectrum from comfort care to selected intervention
- Antenatally: Non-directive counselling; termination or continuation; vaginal delivery preferred; CS not for fetal indication alone
- Cardiac surgery: No longer absolute contraindication — case-by-case decision after MDT discussion
- Feeding: Oral → NG → gastrostomy (graduated approach depending on goals)
- Palliative care: Central to management — symptom control, family bonding, memory making, bereavement support
- Genetic counselling: Low recurrence risk for full trisomy; parental karyotyping essential for translocation type; reproductive options: PGD and prenatal diagnosis [7]
High Yield Summary — Complications of Trisomy 18
- Leading cause of death: Central apnoea (brainstem malformation) and cardiac failure (VSD + polyvalvular disease)
- Cardiac: CHF → pulmonary hypertension → Eisenmenger (if survives long enough); arrhythmias; IE (rare)
- Neurological: Seizures, central apnoea, profound intellectual disability, feeding incoordination → aspiration
- Growth: Severe failure to thrive (multi-factorial: cardiac, feeding, intrinsic growth impairment)
- Renal: Renal failure from structural anomalies; recurrent UTIs
- GI: OA/TOF; omphalocele complications; malrotation/volvulus; GOR → aspiration
- Infectious: Recurrent respiratory infections, sepsis, otitis media
- Ophthalmological: Congenital cataract [6]
- Rare/long-term: Hepatoblastoma [10] (testable association); Wilms tumour; chronic lung disease
- Iatrogenic: Post-surgical complications (cardiac, GI)
- Psychosocial: Parental grief, sibling impact, decision-making burden, mental health
- Prognosis: median survival 14 days; only 5% reach 1 year [1]
Patau Syndrome (trisomy 13)
Patau syndrome is a severe chromosomal disorder caused by an extra copy of chromosome 13, presenting at birth with holoprosencephaly, cleft lip/palate, polydactyly, and major cardiac defects, with most affected infants dying within the first year of life.
Down Syndrome (trisomy 21)
Down syndrome is a genetic condition caused by the presence of an extra copy of chromosome 21, typically apparent from birth, resulting in characteristic facial features, intellectual disability of variable degree, and associated congenital anomalies such as cardiac defects.