Is Williams-Beuren syndrome associated with Obstructive Sleep Apnea (OSA)?

Williams-Beuren Syndrome and Obstructive Sleep Apnea

What is Williams-Beuren Syndrome?

Williams-Beuren syndrome (WBS) is a multisystem genetic disorder caused by a heterozygous microdeletion of 1.5-1.8 Mb on chromosome 7q11.23, containing 26-28 genes including the elastin (ELN) gene, with a prevalence of approximately 1 in 7,500 live births. 1

Key Clinical Features

• Cardiovascular manifestations occur in 80% of patients, most commonly supravalvular aortic stenosis (SVAS), due to elastin gene deletion affecting connective tissue 1
• Distinctive facial dysmorphology is present in 100% of cases 1
• Intellectual disability affects 75% of individuals, with a characteristic cognitive profile seen in 90% 1
• Idiopathic hypercalcemia occurs in 15-45% of patients 1
• Elastin arteriopathy manifests as vascular abnormalities including hypoplasia of the aorta, coronary ostial involvement, and stenosis of major arterial branches 1

Additional Systemic Complications

• Gastrointestinal problems including diverticular disease, constipation, and bladder/bowel diverticula occur frequently 2, 3
• Endocrine abnormalities such as abnormal glucose tolerance and hypothyroidism are common 2
• Musculoskeletal features include inguinal hernias and orthopedic problems related to connective tissue abnormalities 1
• Sensorineural hearing loss is frequently observed in young adults with WBS 2

Association with Obstructive Sleep Apnea

While the provided evidence does not directly establish a specific association between Williams-Beuren syndrome and obstructive sleep apnea, the cardiovascular complications and anatomic features of WBS create plausible risk factors for OSA that warrant clinical vigilance.

Indirect Risk Factors in WBS

• Cardiovascular disease and hypertension are highly prevalent in WBS patients 2, and these conditions are known to be associated with OSA in the general population 1, 4
• Anatomic abnormalities affecting connective tissue throughout the body, including the upper airway structures, could theoretically predispose to airway obstruction during sleep 1
• Hypotonia (though more characteristic of Prader-Willi syndrome) and structural abnormalities may contribute to upper airway compromise 1

Clinical Monitoring Recommendations

Given the high burden of cardiovascular disease in WBS and the known association between cardiovascular complications and OSA, screening for sleep-disordered breathing should be considered in WBS patients, particularly those with:

• Unexplained hypertension that is difficult to control, as OSA is a known contributor to resistant hypertension 1, 2
• Cardiovascular symptoms including exertional dyspnea, as these may reflect both cardiac disease and sleep-disordered breathing 1
• Behavioral changes, cognitive impairment, or nocturia, which are common presenting features of OSA 1

Screening Approach

• Question all WBS patients about cardinal OSA symptoms: excessive daytime sleepiness, snoring, witnessed apneas, morning headaches, and nocturia 1
• Obtain history from bed partners or caregivers when possible, as patients may not recognize their own symptoms 1
• Consider polysomnography (PSG) in WBS patients with suggestive symptoms or unexplained cardiovascular complications, as PSG is the gold standard for OSA diagnosis 1, 4

Important Caveats

• The evidence base does not specifically document OSA prevalence in WBS, unlike other genetic syndromes such as Prader-Willi syndrome where OSA is well-established (>80% prevalence) 1
• Cardiac catheterization may be particularly risky in WBS patients, especially when evaluating cardiovascular disease, so non-invasive assessment should be prioritized when possible 1
• Lifelong cardiovascular monitoring is mandatory in WBS regardless of OSA status, given the high prevalence of progressive vascular disease 1