Edwards’ Syndrome (Trisomy 18)
Edward syndrome (Trisomy 18) is a severe chromosomal condition resulting from an extra copy of chromosome 18.
The majority of cases (>90%) are due to meiotic non-disjunction, a random error in cell division where the two copies of chromosome 18 fail to separate during gamete formation (either the egg or sperm). This is not hereditary.
Rarer forms include mosaic trisomy 18 (the extra chromosome is only in some of the body’s cells, potentially leading to a milder phenotype and longer survival) and partial trisomy 18 (a portion of the extra chromosome is attached to another chromosome, with prognosis depending on the specific genes involved).
Diagnosis and Clinical Features
Diagnosis is often suspected on antenatal scans due to multiple congenital anomalies and symmetrical intrauterine growth restriction (IUGR).
Rapid testing with FISH or a full karyotype (Micro-Array) confirms the presence of the additional chromosome 18. In the UK, this is guided by the NHS Genomic Medicine Service (GMS) National Genomic Test Directory.
Physical anomalies typically seen at birth include:
Symmetrical IUGR and low birth weight with microcephaly.
Craniofacial features: prominent occiput, low-set ears, tight palpebral fissures, small mouth and jaw.
Congenital heart disease (CHD) is highly prevalent (>90% of cases), most commonly a VSD, but other complex lesions such as Tetralogy of Fallot or hypoplastic left heart syndrome are also seen.
Limb anomalies: hypoplastic nails, clenched hands with overlapping digits (specifically the 2nd over the 3rd and 5th over the 4th), and “rocker-bottom” feet.
Generalised hypertonia and a short sternum.
Other systems can be affected, including the gastrointestinal (e.g., omphalocele), genitourinary (e.g., horseshoe kidney), and neurological systems.
Prognosis and Management in the UK
Counselling is essential at the point of suspicion, both antenatally and after birth. This should be a multidisciplinary effort, involving obstetrics, fetal medicine, paediatrics, and genetic counselling, with resources like Antenatal Results and Choices (ARC) and SOFT UK signposted for parental support.
The majority of affected pregnancies result in miscarriage or stillbirth. For live births, mortality is high in the first few days and weeks of life, with median survival cited as approximately 14 days in a large UK study.
Recent data from the UK suggests a 1-year survival rate of around 8%, with survival being significantly longer in girls than in boys.
There is a paradigm shift in management, moving from a purely palliative approach to a more nuanced, individualised assessment. While prognosis remains poor, there is growing evidence that selective, supportive medical interventions (e.g., cardiac surgery, gastrostomy for feeding issues, respiratory support) can extend life.
This shift presents ethical challenges and requires a balance between aggressive intervention and a palliative care pathway. Management is a shared decision with the family, respecting their values and wishes. Children’s palliative care is a crucial component, aiming to improve quality of life for the child and support the family, often provided in hospices or at home.
Recent developments have focused on this individualised approach, acknowledging that children with Edwards’ syndrome are not a uniform group. The presence of mosaicism and the specific organ systems affected can greatly influence long-term survival and developmental outcomes. There is an increasing recognition that some children with Trisomy 18 can slowly meet developmental milestones, communicate, and lead lives of perceived quality, a point that should be included in counselling.