What are the common causes of hypersomnolence in a patient with Trisomy 21 (Down syndrome)?

Common Causes of Hypersomnolence in Trisomy 21 (Down Syndrome)

Obstructive sleep apnea syndrome (OSAS) is the most common cause of hypersomnolence in patients with Down syndrome, followed by post-adenotonsillectomy OSAS, hypoventilation, and nocturnal hypercapnia. 1

Primary Respiratory-Related Causes

Obstructive Sleep Apnea Syndrome

• OSAS represents the leading cause of hypersomnolence in Down syndrome patients due to multiple anatomical abnormalities including macroglossia, adenotonsillar hypertrophy, laryngomalacia, smaller and narrow trachea, and tracheo- and bronchomalacia 1
• Oedema in soft tissues of the upper airway and altered regulatory control of pharyngeal muscles, combined with reduced activity in respiratory centers, significantly increase OSAS incidence 1
• OSAS can persist or develop even after adenotonsillectomy, requiring ongoing monitoring and potential noninvasive ventilation (NIV) support 1

Hypoventilation and Nocturnal Hypercapnia

• These conditions are common indications for NIV support in Down syndrome patients and directly contribute to daytime hypersomnolence 1
• Respiratory anatomical malformations and intellectual disabilities can affect adherence to NIV treatment, potentially worsening hypersomnolence 1

Structural Cardiopulmonary Abnormalities

Lower Airway and Alveolar Pathology

• Children with Down syndrome have up to 25% decrease in alveoli number and branch generation number, contributing to chronic respiratory insufficiency 1
• Pulmonary hypoplasia, enlarged alveolar airspaces, and subpleural cysts further compromise respiratory function and can cause daytime sleepiness 1

Cardiovascular Complications

• High incidence of congenital heart diseases (atrioventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot) negatively impacts cardiorespiratory function and contributes to fatigue and hypersomnolence 1
• Pulmonary hypertension from vascular abnormalities can worsen sleep quality and daytime alertness 1

Secondary Medical Causes

Metabolic and Endocrine Disorders

• Hypothyroidism is a treatable cause of hypersomnia that should be screened for in all Down syndrome patients with hypersomnolence 2, 3
• Laboratory testing including thyroid function tests should be performed to rule out underlying metabolic conditions 2

Medication-Related Causes

• Sedating medications including benzodiazepines, opioids, antihistamines, and certain antidepressants can cause or worsen hypersomnolence 2, 3
• This is particularly important as Down syndrome patients often take multiple medications for comorbid conditions 2

Diagnostic Approach Specific to Down Syndrome

Essential Evaluations

• Polysomnography (PSG) is critical to diagnose OSAS and quantify its severity in Down syndrome patients presenting with hypersomnolence 1, 2
• Multiple Sleep Latency Test (MSLT) should be performed after PSG to rule out central disorders of hypersomnolence if OSAS is adequately treated but hypersomnolence persists 2
• Brain MRI is recommended to identify structural causes, particularly given the increased risk of early-onset Alzheimer's disease in Down syndrome 2

Laboratory Screening

• Thyroid function tests, complete blood count, serum chemistry, and liver function tests should be obtained 2
• Ferritin levels should be checked if restless legs syndrome is suspected 3

Common Pitfalls

• Failing to recognize that OSAS in Down syndrome often requires NIV support rather than just adenotonsillectomy 1
• Assuming hypersomnolence is simply part of the intellectual disability rather than investigating treatable causes 4
• Not recognizing that multiple causes often coexist in Down syndrome patients, requiring comprehensive evaluation of respiratory, cardiac, metabolic, and medication-related factors 1, 2
• Overlooking persistent or recurrent OSAS after adenotonsillectomy, which is common in this population 1