85  Edward’s Syndrome

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85.1 Introduction

Edward syndrome, or Trisomy 18, is the second most common autosomal trisomy after Down syndrome, associated with a high rate of perinatal mortality and profound developmental abnormalities. First described by John Hilton Edward in 1960, the condition arises due to an extra copy of chromosome 18. The estimated prevalence is approximately 1 in 5,000 live births, but the actual incidence is higher due to early embryonic and fetal losses. Edward syndrome has a significant impact on physical, cognitive, and systemic development, with most affected infants demonstrating severe disability and reduced survival.

85.2 Definition

Edward syndrome is a chromosomal disorder caused by the presence of an extra copy of chromosome 18, resulting in multisystem abnormalities. The condition is characterized by intrauterine growth restriction (IUGR), distinctive craniofacial and limb features, and major organ defects. Based on the cytogenetic findings, Edward syndrome is classified into:

  1. Full Trisomy 18 (90%): The extra chromosome 18 in all cells due to non-disjunction during meiosis.
  2. Mosaic Trisomy 18 (5–10%): Some cells have a normal karyotype, while others exhibit trisomy 18 due to post-zygotic non-disjunction.
  3. Partial Trisomy 18 (<1%): A part of chromosome 18 is duplicated and attached to another chromosome.

85.3 Genetics

The underlying cause of Edward syndrome is the presence of three copies of chromosome 18, which leads to the overexpression of genes located on this chromosome. Chromosome 18 contains approximately 500–600 genes, many involved in critical developmental pathways.

  1. Mechanism of Trisomy 18:
    • The most common cause is meiotic nondisjunction, particularly in maternal gametes.
    • Advanced maternal age is a significant risk factor, as with other trisomies.
  2. Mosaicism occurs when nondisjunction occurs after fertilization, resulting in a mixture of normal and trisomic cells. Mosaic cases often have milder phenotypes than full trisomy.
  3. Inheritance:
    • Most cases are sporadic and not inherited.
    • Rarely, partial trisomy may result from a balanced translocation in one parent.

85.4 Clinical Features

Edward syndrome presents a constellation of physical, neurological, and systemic abnormalities, which are often apparent prenatally or at birth.

  1. Prenatal Features:
    • Severe intrauterine growth restriction (IUGR)
    • Polyhydramnios or oligohydramnios
    • Structural anomalies detectable on fetal ultrasound (e.g., cardiac defects, clenched hands, and overlapping fingers)
  2. Craniofacial Features:
    • Microcephaly
    • Prominent occiput
    • Low-set, malformed ears
    • Micrognathia (undersized jaw)
    • Cleft lip and/or palate (less common)
  3. Limb and Skeletal Abnormalities:
    • Clenched hands with overlapping fingers
    • Rocker-bottom feet
    • Hypoplastic nails
    • Short sternum
  4. Neurological Features:
    • Severe intellectual disability
    • Hypotonia or hypertonia
    • Seizures
  5. Cardiac Abnormalities:
  6. Other Systemic Abnormalities:
    • Gastrointestinal: Omphalocele, esophageal atresia, or malrotation.
    • Renal: Horseshoe kidney, hydronephrosis, or renal agenesis.
    • Respiratory: Hypoplastic lungs in some cases.
  7. Postnatal Features:
    • Failure to thrive due to feeding difficulties.
    • Persistent respiratory infections.
    • Limited spontaneous movement.

85.5 Investigations

A combination of prenatal and postnatal diagnostic tools confirms Edward syndrome and identifies associated anomalies.

  1. Prenatal Investigations:
    • Ultrasound Findings:
      • IUGR
      • Structural anomalies (e.g., cardiac defects, clenched hands, omphalocele)
    • Maternal Serum Screening:
      • Low alpha-fetoprotein (AFP) levels, unconjugated estriol (uE3), and free β-hCG.
    • Non-Invasive Prenatal Testing (NIPT):
      • Detects fetal cell-free DNA in maternal blood with high sensitivity and specificity for trisomy 18
    • Invasive Diagnostic Testing:
      • Amniocentesis (after 15 weeks): Definitive karyotyping to confirm trisomy 18.
      • Chorionic Villus Sampling (CVS) (10–13 weeks): Early diagnostic confirmation
  2. Postnatal Investigations:
    • Cytogenetic Testing:
      • Karyotyping remains the gold standard for diagnosis.
      • Fluorescence in situ hybridization (FISH) or chromosomal microarray analysis for rapid diagnosis.
    • Echocardiogram:
      • Essential to identify and evaluate congenital heart defects.
    • Renal Ultrasound:
      • Detects structural anomalies like horseshoe kidney or hydronephrosis.
    • Other Tests:
      • Brain imaging (MRI or CT) for structural abnormalities.
      • Hearing and vision screening.

85.6 Treatment

Edward syndrome does not have a curative treatment, and management focuses on supportive and palliative care to improve the quality of life. Treatment depends on the severity of symptoms and associated anomalies.

  1. Neonatal Care: Support for feeding difficulties, often requiring nasogastric tube feeding. Management of respiratory distress with oxygen therapy or mechanical ventilation.
  2. Cardiac Care: Severe cardiac defects may require surgical intervention, but many families opt for conservative management due to the poor prognosis.
  3. Surgical Management: Repairs for gastrointestinal anomalies like esophageal atresia or omphalocele if compatible with survival.
  4. Developmental Support: Physical, occupational, and speech therapy can be introduced to optimize motor skills and communication, although progress is often limited.
  5. Palliative Care: Comfort-focused care is essential for managing pain, feeding issues, and respiratory infections.
    • Hospice care is often recommended for severe cases.

85.7 Counselling

Counseling is vital to managing Edward syndrome and providing support to families before and after diagnosis.

  1. Prenatal Counselling:
    • Inform parents about the diagnosis, prognosis, and potential outcomes.
    • Discuss available options, including continuation or termination of pregnancy.
    • Offer psychological support and refer to genetic counseling
  2. Postnatal Counselling:
    • Educate families on the medical challenges and potential interventions.
    • Provide information on support systems and resources.
    • Encourage the involvement of multidisciplinary teams, including neonatologists, geneticists, and social workers.
  3. Genetic Counselling:
    • For families with a history of Edward syndrome, offer genetic testing to identify potential translocations or chromosomal abnormalities in parents.
    • Explain recurrence risks:
      • <1% for full trisomy 18 due to de novo events.
      • Higher if a parent is a carrier of a balanced translocation.
  4. Psychosocial Support:
    • Assist families in coping with grief and decision-making.
    • Connect them with support groups and advocacy organizations

85.8 Conclusion

Edward syndrome is a severe chromosomal disorder characterized by profound developmental and physical abnormalities, with a high risk of perinatal mortality. Advances in prenatal diagnostic techniques allow for early detection and informed decision-making. While there is no definitive cure, multidisciplinary care focusing on symptom management, supportive therapy, and counseling is critical in improving the quality of life for affected individuals and their families. Further research into the molecular mechanisms of trisomy 18 may offer insights into potential therapeutic strategies in the future.