What is Edward Syndrome (Trisomy 18)?
Edward syndrome (also called trisomy 18) is a chromosomal disorder caused by the presence of an extra chromosome 18, characterized by multiple congenital anomalies, severe neurodevelopmental disability, and historically high mortality, though survival rates are improving with modern interventions. 1
Epidemiology and Genetics
Edward syndrome occurs in approximately 3 per 10,000 live births in the United States, making it the second most common autosomal trisomy after Down syndrome (trisomy 21). 1 The condition affects females 2-3 times more often than males among live births. 1
Approximately 95% of cases involve full trisomy 18, with the extra chromosome present in all cells, and risk increases with advancing maternal age. 1 The remaining cases include:
- Mosaic trisomy 18: Extra chromosome present in only some cells, typically with milder presentations
- Partial trisomy 18: Only part of chromosome 18 is duplicated, also with more variable clinical features 1
Clinical Features
The syndrome presents with a constellation of major and minor anomalies affecting multiple organ systems:
Cardiac Abnormalities
Congenital heart disease occurs in 80-90% of infants with trisomy 18, representing the most common major malformation. 1 Common defects include ventricular septal defects and other complex cardiac anomalies.
Neurological Features
- Severe neurodevelopmental disabilities affecting tone and development
- Seizures in some cases
- Persistent neurologic impairment throughout life 1
Characteristic Physical Features
- Distinctive craniofacial appearance
- Clenched fists with overlapping fingers (pathognomonic finding)
- Small fingernails and underdeveloped thumbs
- Hand anomalies 1
Other Common Anomalies
- Uteroplacental abnormalities and prematurity
- Possible endocrine/hormonal abnormalities
- Growth restriction (prenatal and postnatal)
- Feeding difficulties requiring enteral nutrition 2
Prognosis and Survival
Historically, trisomy 18 has been associated with very high mortality, but outcomes are evolving with changing management approaches:
- 52.5% of live-born infants survive beyond the first week 1
- 10-25% survive beyond the first year 1
- 12.3% survive beyond 5 years 1
The median survival has traditionally ranged from 2.5 to 14.5 days, though this is improving with interventions. 3 Major causes of death include central apnea, cardiac failure, respiratory insufficiency, upper airway obstruction, and aspiration. 2
Diagnosis
Prenatal Diagnosis
Most cases are now identified before birth through:
- Noninvasive prenatal screening (NIPS) - though diagnostic certainty may be lower than parents realize
- Fetal ultrasonography showing characteristic findings (increased nuchal translucency, growth retardation, choroid plexus cysts, overlapping fingers, congenital heart defects)
- Amniocentesis for definitive confirmation 1
Postnatal Diagnosis
When diagnosis occurs after birth (due to limited prenatal care or mild phenotype), confirmation is obtained through genetic testing of blood, saliva, or tissue samples. 1 Withdrawing life-sustaining interventions based solely on unconfirmed suspicion of trisomy 18 is rarely justifiable - diagnostic confirmation should be pursued. 1
Management Considerations
The approach to care has evolved significantly, with increasing recognition that selected interventions can improve survival and quality of life:
Cardiac Surgery
Multiple studies demonstrate potential benefit for cardiac surgery in patients with trisomy 18, though with higher perioperative mortality. 1 Infants requiring mechanical ventilation preoperatively have the poorest outcomes. 1 Both corrective and palliative cardiac procedures are now offered at some centers.
Supportive Care
Comprehensive multidisciplinary management addresses:
- Respiratory support (including potential home oxygen therapy)
- Feeding support and nutritional management
- Monitoring for complications across multiple organ systems 4
Important caveat: There is significant institutional variation in which interventions are offered to infants with trisomy 18, and families may need to seek transfer for second opinions if desired interventions are not available at the birth hospital. 1