Upper Airway Obstruction in Edwards Syndrome (Trisomy 18)
Upper airway obstruction in infants with Edwards syndrome is caused by a combination of anatomical abnormalities including micrognathia, glossoptosis, laryngomalacia, tracheomalacia/bronchomalacia, and central apnea, with tracheobronchomalacia being particularly significant and often underrecognized. 1
Primary Anatomical Causes
The upper airway obstruction in Edwards syndrome stems from multiple structural abnormalities:
Craniofacial and Oropharyngeal Abnormalities
- Micrognathia (small jaw) and glossoptosis (posterior displacement of the tongue) create mechanical obstruction at the pharyngeal level
- These features are part of the characteristic craniofacial dysmorphology seen in trisomy 18 1
Airway Malacia
Tracheobronchomalacia represents a critical and frequently underdiagnosed cause of airway obstruction in this population. This condition involves abnormal collapsibility of the trachea and bronchi, which can cause severe respiratory compromise, particularly during periods of increased respiratory effort 2, 1. When infants with tracheobronchomalacia cry or cough, the increased respiratory effort paradoxically worsens airway collapse, leading to severe hypoxia 2.
Laryngeal Abnormalities
Laryngomalacia (abnormal collapse of supraglottic structures during inspiration) contributes to upper airway obstruction and is more prevalent in Edwards syndrome patients 3.
Central Nervous System Contribution
Central apnea is a major contributor to respiratory insufficiency and represents one of the leading causes of death in Edwards syndrome 4, 1. This results from:
- Altered respiratory control centers
- Reduced activity in brainstem respiratory centers
- Neurological impairment affecting coordination of breathing
The combination of central apnea with anatomical obstruction creates a particularly dangerous situation where both the drive to breathe and the patency of the airway are compromised 1.
Clinical Significance and Recognition
Upper airway obstruction is likely more common than previously recognized and should be actively investigated when families and medical teams opt for full supportive care 1. The obstruction manifests as:
- Stridor or noisy breathing
- Respiratory distress with increased work of breathing
- Episodes of severe hypoxia, particularly with agitation or crying
- Difficulty with mask ventilation and intubation 5
Critical Perioperative Considerations
In the perioperative setting, difficult airway management is a consistent concern. A review of 84 anesthesia encounters in nine Edwards syndrome patients revealed:
- Difficult mask ventilation in multiple cases
- Difficult intubation episodes
- Cardiopulmonary resuscitation required in 6 instances
- One immediate postoperative death 5
The inability to ventilate can rapidly lead to cardiorespiratory arrest in these patients 5.
Pathophysiologic Mechanism
The obstruction becomes particularly severe during periods of respiratory effort because:
- Increased negative intrathoracic pressure during inspiration worsens collapse of malacic airways
- Agitation and crying increase oxygen demand while simultaneously worsening airway patency
- The combination of anatomical narrowing and dynamic collapse creates a vicious cycle 2
Interestingly, sedation can paradoxically improve airway patency by reducing respiratory effort and the associated negative pressure that causes airway collapse. This has been demonstrated with sevoflurane administration, which allowed successful ventilation in a patient who could not be ventilated while awake and struggling 2.
Common Pitfall
The most critical pitfall is underestimating the prevalence and severity of tracheobronchomalacia in Edwards syndrome. This diagnosis requires flexible bronchoscopy for confirmation and should be considered in any infant with Edwards syndrome who has persistent respiratory distress, particularly if symptoms worsen with agitation 2, 1. Clinicians may attribute all respiratory symptoms to central apnea or cardiac disease, missing the treatable component of airway malacia.