SUPERStudy: Edward’s Syndrome (Trisomy 18)

By usmlevideoss

Introduction: Edward’s syndrome, also known as Trisomy 18, is a genetic disorder caused by the presence of an extra chromosome 18. It is associated with severe developmental delays, congenital anomalies, and high mortality, often within the first year of life.

Etiology

  • Caused by nondisjunction of chromosome 18 during meiosis, leading to a full extra copy of chromosome 18 in most cases.
  • Mosaicism (some cells have trisomy 18, while others are normal) or partial trisomy (only a segment of the chromosome is extra) are rarer forms.
  • Advanced maternal age is a risk factor for nondisjunction.

Epidemiology

  • Second most common autosomal trisomy after Down syndrome.
  • Incidence: ~1 in 5,000-6,000 live births.
  • More common in pregnancies but many result in miscarriage or stillbirth.
  • Female predominance (3:1 ratio).

Pathophysiology

The extra chromosome 18 leads to abnormal gene expression, causing disruptions in normal development, particularly of the cardiovascular, craniofacial, and skeletal systems. This results in severe structural abnormalities, growth restriction, and organ dysfunction.

Clinical Manifestations

  • Prenatal findings: Intrauterine growth restriction (IUGR), polyhydramnios, single umbilical artery.
  • Craniofacial features: Micrognathia (small jaw), low-set ears, prominent occiput, small mouth.
  • Hand abnormalities: Overlapping fingers (index over middle, and fifth over fourth).
  • Musculoskeletal: Rocker-bottom feet, short sternum, clenched hands.
  • Cardiovascular: Congenital heart defects (e.g., ventricular septal defect, atrial septal defect, patent ductus arteriosus).
  • Neurological: Severe developmental delays, hypotonia initially (which can progress to hypertonia), seizures.
  • Renal abnormalities: Horseshoe kidney, hydronephrosis.

Diagnosis

  • Prenatal screening: Maternal serum screening (low alpha-fetoprotein, low estriol, low β-hCG), and ultrasound findings.
  • Prenatal confirmation: Amniocentesis or chorionic villus sampling (CVS) with karyotyping.
  • Postnatal diagnosis: Karyotype analysis confirms trisomy 18.
  • Imaging: Echocardiogram for congenital heart defects.

Treatment

  • No curative treatment; care focuses on palliative and supportive management.
  • Neonatal care: Monitoring of feeding and breathing, oxygen therapy, and management of congenital defects.
  • Surgical intervention: Occasionally for heart defects, but often limited due to poor prognosis.
  • Multidisciplinary care: Includes cardiology, neurology, and palliative care teams.

Prognosis

  • Poor prognosis with a high mortality rate.
  • More than 90% of affected infants die within the first year of life, usually due to heart failure or respiratory complications.
  • Survival beyond infancy is rare, with significant physical and intellectual disabilities.

Memory Aid or Mnemonic:

“PRINCE Edwards”

P: Prominent occiput, Ptosis 

R: Rocker-bottom feet

I: Intellectual disability

N: Nondisjunction (trisomy 18)

C: Clenched fists with overlapping fingers

E: Ear abnormalities (low-set ears)

E: Extra chromosome 18 (Trisomy 18)  

D: Developmental delay and intellectual disability  

W: Weak cry and failure to thrive  

A: Abnormalities in hands (clenched fists, overlapping fingers)

R: Rocker-bottom feet  

D: Distinct facial features (micrognathia, low-set ears, small head), death in early infancy   

S: Severe congenital heart defects (e.g., VSD, ASD), shortened big toe, small mandible, short sternum, small pelvis, syndactyly  

OR

“Eighteen’s Edge: Clenched, Crossed, Cardiac”

– Eighteen: Refers to Trisomy 18.

– Edge: Highlights the severity; most babies don’t survive long post-birth.

– Clenched: Babies often have clenched fists with overlapping fingers.

– Crossed: Common feature of crossed legs (rocker-bottom feet).

– Cardiac: High incidence of heart defects.

 

SUPERPoint:Edward syndrome (Trisomy 18) is a severe genetic disorder characterized by multiple congenital anomalies, most commonly involving the heart, hands, feet, and craniofacial structures, with a high mortality rate in infancy.

SUPERFormula: Baby presents with micrognathia +  prominent occiput + clenched hands with overlapping fingers + rocker-bottom feet + congenital heart defects + Trisomy 18 (nondisjunction) + growth restriction = Edward’s  syndrome 

Reference: Developmental Diseases of the Nervous System. In: Ropper AH, Samuels MA, Klein JP, Prasad S. eds. Adams and Victor’s Principles of Neurology, 12e. McGraw-Hill Education; 2023.