What makes children with Down syndrome (DS) more susceptible to Obstructive Sleep Apnea (OSA)?

Increased Susceptibility to OSA in Children with Down Syndrome

Children with Down syndrome have markedly increased susceptibility to OSA due to multiple anatomical abnormalities of the upper airway combined with neurological factors affecting respiratory control. 1

Upper Airway Anatomical Factors

The primary drivers of OSA susceptibility in children with DS are structural abnormalities throughout the upper airway:

Craniofacial and Oropharyngeal Abnormalities

• Midfacial and mandibular hypoplasia create a fundamentally smaller airway space, reducing the cross-sectional area available for airflow 1, 2
• Macroglossia (enlarged tongue relative to oral cavity size) or glossoptosis with relative macroglossia occupies disproportionate space in an already compromised airway 1
• Adenotonsillar hypertrophy is extremely common and further narrows the pharyngeal airway 1
• Smaller and narrower trachea extends the anatomical compromise beyond just the pharynx 1
• Oropharyngeal dimensions are significantly reduced in children with DS compared to typically developing children with similar OSA severity 3

Structural Airway Pathology

• Laryngomalacia causes dynamic collapse of supraglottic structures during inspiration 1
• Tracheo- and bronchomalacia result in airway collapse during breathing 1
• Subglottic and/or tracheal stenosis create fixed points of obstruction 1
• Tracheal-bronchus obstruction further compromises airway patency 1

Neuromuscular and Respiratory Control Factors

Beyond structural issues, children with DS have significant functional impairments:

Muscle Tone Abnormalities

• Generalized hypotonia affects pharyngeal dilator muscles, reducing their ability to maintain airway patency during sleep 1, 4, 5
• Altered regulatory control of pharyngeal muscles impairs the normal protective reflexes that prevent airway collapse 1

Ventilatory Control Dysfunction

• Reduced activity in respiratory centers decreases the drive to breathe 1
• Decreased peripheral chemoreceptor sensitivity leads to blunted responses to hypoxia and hypercapnia 3
• Reduced controller gain and chemical loop gain result in inadequate ventilatory responses to respiratory challenges 3
• Normal central chemosensitivity but decreased peripheral sensitivity explains the nocturnal alveolar hypoventilation characteristic of DS 3

Soft Tissue and Mucosal Factors

Additional tissue-level abnormalities compound the problem:

• Oedema in soft tissues of the upper airway increases tissue bulk and reduces airway caliber 1
• Impaired mucus production and ciliopathies lead to mucus accumulation that further obstructs airways 1
• Impaired mucociliary clearance prevents effective clearing of secretions 1

Lower Airway and Pulmonary Contributions

While OSA is primarily an upper airway disorder, lower respiratory abnormalities in DS contribute to overall respiratory compromise:

• Up to 25% decrease in alveolar number and branch generation reduces respiratory reserve 1
• Pulmonary hypoplasia with enlarged alveolar airspaces impairs gas exchange 1

Cardiovascular Comorbidities

Congenital heart disease is highly prevalent in DS and exacerbates OSA:

• High incidence of congenital heart defects (atrioventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot) negatively impacts cardiorespiratory function 1
• These cardiac abnormalities worsen the pathophysiology of respiratory failure and increase OSA severity 1

Clinical Implications and Prevalence

The cumulative effect of these factors results in extraordinarily high OSA prevalence:

• 66.4% overall prevalence of OSA in children with DS, with 53.8% prevalence even in those without snoring history 1
• 59% prevalence in another cohort, with significantly higher apnea-hypopnea index compared to matched controls 5
• Moderate to severe OSA (OAHI >5/h) occurs in 14% of very young children with DS 6
• 34% have severe OSA (AHI ≥10/h) compared to 18% in typically developing children 7
• Nearly 40% of children with DS and OSA do not have habitual snoring, making clinical screening unreliable 5

Age-Related Patterns

OSA severity follows a distinctive age distribution in DS:

• Highest severity occurs in young children (<3 years) and adolescents (>10 years), following a "U-shaped" distribution 7
• Younger age is associated with more severe disease in early childhood 1
• The obstructive component increases significantly with age and BMI, while central apnea is most common in very young children 1

Common Clinical Pitfall

A critical error is relying on snoring history or tonsillar size to predict OSA severity in children with DS. Tonsillar size does not predict OSA severity 6, and a substantial proportion of children with DS and OSA do not snore habitually 5. Population-based polysomnography screening is recommended for all children with DS regardless of symptoms 1, 6.