Edwards Syndrome (Trisomy 18)
Summary
Edwards Syndrome (Trisomy 18) is a severe chromosomal disorder characterized by the presence of an extra copy of chromosome 18. It is the second most common autosomal trisomy after Down Syndrome (T21). It is associated with a distinct phenotype of severe intrauterine growth restriction (IUGR), craniofacial dysmorphism, limb abnormalities, and organ defects (Cardiac/Renal). The prognosis is poor, with most fetuses dying in utero or shortly after birth. However, the label "incompatible with life" is outdated; "life-limiting" is preferred, as some children (5-10%) survive infancy with significant neurodisability. [1,2]
Key Facts
- The "Overlapping Fingers": The classic pathognomonic sign. The index finger crosses over the middle finger, and the little finger crosses over the ring finger.
- Rocker Bottom Feet: The feet have a convex sole and a prominent calcaneus, resembling the rocker of a rocking chair.
- Cardiac: >90% of affected infants have structural heart disease, most commonly a large Ventricular Septal Defect (VSD) and polyvalvular dysplasia.
Clinical Pearls
The "Small" Baby: Edwards babies are invariably small for gestational age (IUGR). A small baby with polyhydramnios (due to poor swallowing) should raise immediate suspicion.
Occiput: Unlike Patau Syndrome (T13) where the forehead is sloped and defects are midline (clefts), Edwards babies have a petite face with micrognathia (small chin) but a very Prominent Occiput (back of the head shelves out).
Mosaicism: 5% of cases are "Mosaic Trisomy 18", where some cell lines are normal. These individuals may have a much milder phenotype and longer survival.
Incidence
- Live Births: 1 in 6,000.
- Conception: Much higher, but high rate of spontaneous miscarriage / stillbirth.
- Gender: Female > Male (3:1). Male fetuses are lost more frequently in utero.
Risk Factors
- Maternal Age: Strong association (Non-disjunction error increases with oocyte age).
- Not inherited (sporadic) in 95% of cases.
Mechanism
- Non-Disjunction: In Meiosis II (Maternal), the pair of chromosome 18s fails to separate. The zygote gets 3 copies.
- Organogenesis: The extra genetic material disrupts gene expression during critical developmental windows (weeks 3-8), causing midline defects, cardiac septation failure, and brain anomalies.
Craniofacial
Limbs
Systemic
- Growth: Plot weight (usually less than 3rd centile).
- Face: Profile view for micrognathia/occiput.
- Hands/Feet: Check the classic signs.
- Heart: Pan-systolic murmur (VSD).
Antenatal Screening
- Combined Test: Low PAPP-A, Low hCG, Increased Nuchal Translucency.
- Quadruple Test: Low AFP, Low uE3, Low hCG. (All markers are low in T18, unlike T21 where hCG is high).
- NIPT: >99% sensitivity.
Postnatal Diagnosis
- QF-PCR: Rapid result (24-48h).
- Karyotype: Full chromosomal analysis (Gold Standard) to rule out translocations.
- Echo: To assess cardiac lesions.
- Renal US: To check for structural anomalies.
Management Algorithm
SUSPECTED TRISOMY 18
(Dysmosphism + IUGR + Murmur)
↓
CONFIRM DIAGNOSIS
(Rapid FISH / PCR)
↓
┌─────────────┼─────────────┐
PRENATAL POSTNATAL SURVIVORSHIP
↓ ↓ ↓
COUNSELLING PALLIATIVE SUPPORTIVE
(Termination) CARE PLAN CARE
OR OR (NG Feeding)
CONTINUE ACTIVE CARE (Physio)
(Individual)
1. Delivery Room
- Many parents choose "Comfort Care" (no resuscitation/intubation).
- Others may request active measures. Guidelines now suggest individualised plans rather than blanket "Do Not Resuscitate".
2. Neonatal Care
- Palliative: Symptom management (secretions, apnoea). Hospice support.
- Feeding: Most require Nasogastric (NG) tube due to unsafe swallow/micrognathia. Risk of aspiration is high.
- Apnoea: Central apnoea is the leading cause of early death.
3. Surgical
- Traditionally, surgery (cardiac repair) was denied.
- Recent trends show cardiac surgery can improve survival in selected infants, though it does not change the neurodevelopmental outcome.
- Central Apnoea.
- Cardiac Failure: From large shunts (VSD).
- Wilms Tumour: Increased risk (screening required if surviving).
- Scoliosis.
- Median Survival: 5-15 days.
- Survival to 1 year: 5-10%.
- Long term: Those who survive childhood usually have profound disability (non-verbal, dependent for all care).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Fetal Anomaly Screening | NHS FASP | Screening pathway details. |
| Trisomy 13/18 | AAP (USA) | Balanced approach: Support parental goals, avoid "lethal" label. |
Landmark Data
1. SOFT (Support Organization for Trisomy)
- Parental advocacy has shifted the medical paradigm from "futility" to "quality of life" and shared decision making.
- Studies (Kosho et al) confirm that intensive care can prolong life, but profound disability remains unmodified.
What is Edwards Syndrome?
It is a rare genetic condition where a baby is born with 3 copies of chromosome number 18 instead of the usual 2. This extra genetic information disrupts the baby's normal development.
Is it inherited?
Usually not. It is typically a "one-off" event that happens when the egg or sperm is being made. It is not something you caused.
What does it mean for my baby?
Babies with Edwards syndrome are usually very small and frail. They often have problems with their heart and feeding. Sadly, because the condition affects so many organs, many babies die before or shortly after birth.
Is there a cure?
There is no cure for the chromosomal problem. We cannot remove the extra chromosome. Care focuses on keeping the baby comfortable, loved, and helping with feeding and breathing for as long as they are with us.
Primary Sources
- Cereda A, Carey JC. The trisomy 18 syndrome. Orphanet J Rare Dis. 2012;7:81.
- Kosho T, et al. Natural history and palliative care in trisomy 18. Am J Med Genet C Semin Med Genet. 2016.
- NICE. Antenatal care for uncomplicated pregnancies. (Screening section).
Common Exam Questions
- Diagnosis: "Clenched hand with overlapping fingers?"
- Answer: Edwards Syndrome (T18).
- Screening: "Quad test result?"
- Answer: All Low (AFP, uE3, hCG). (Downs has High hCG).
- Anatomy: "Commonest cardiac defect?"
- Answer: VSD (Ventricular Septal Defect).
- Genetics: "Recurrence risk?"
- Answer: less than 1% (if nondisjunction). Higher if translocation (check parents).
Viva Points
- Rocker Bottom Feet: Also seen in Patau Syndrome (T13). Distinction is the hands and face (No cleft in Edwards).
- Ethics: Discuss the shift from "Lethal" to "Life-Limiting". How would you counsel a parent demanding cardiac surgery for a T18 baby? (Balance beneficence/non-maleficence, resource allocation, and parental autonomy).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.