Obstructive Sleep Apnoea in Ehlers-Danlos Syndrome (OSA in EDS)

Ehlers-Danlos Syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. EDS features such as genetically related cartilage defects, craniofacial abnormalities and increased pharyngeal collapsibility have been proposed to cause obstructive sleep apnoea (OSA). There is evidence from studies based on questionnaires that EDS patients might be more frequently affected by OSA and sleep disturbances than the general population. However, the actual prevalence of OSA in patients with EDS is unknown.

Aortic root dilation and dissection are common complications of EDS and little is known about the underlying risk factors. Preliminary evidence suggests a link with OSA but this has not yet been investigated.

The primary objective of this study is to assess the prevalence of OSA in EDS-patients (100) compared to a matched control group (100). The secondary objective of this pioneer study is to assess whether there is a relationship between OSA severity and aortic diame-ter/craniofacial abnormalities in EDS patients.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea; Ehlers-Danlos Syndrome

Detailed Description

Ehlers-Danlos Syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. EDS features such as genetically related cartilage defects, craniofacial abnormalities and increased pharyngeal collapsibility have been proposed to cause obstructive sleep apnoea (OSA). There is evidence from studies based on questionnaires that EDS patients might be more frequently affected by OSA and sleep disturbances than the general population. However, the actual prevalence of OSA in patients with EDS is unclear.

Aortic dilation and dissection are complications associated with EDS and little is known about the underlying risk factors. Preliminary evidence suggests a link with OSA but this has not yet been investigated.

The primary objective of this study is to assess the prevalence of OSA in EDS-patients compared to a matched control group. The secondary objective of the study is to assess whether there is a relationship between OSA severity and craniofacial phenotypes / aortic diameter in EDS patients.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Division of Pulmonology, University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Prospective case-control study including EDS patients and controls matched for age, gender, height and weight. The following outcomes will be assessed: 1) apnoea-hypopnoea index, 2) sleep-related questionnaires, 3) medical chart review, and 4) echocardiography

Description

Inclusion Criteria:

• Informed consent
• Diagnosis of Ehlers-Danlos Syndrome (not for control group)

Exclusion Criteria:

• Moribund or severe disease prohibiting protocol adherence
• Continuous positive airway pressure treatment for OSA during sleep study
• Physical or intellectual impairment precluding informed consent or protocol adherence
• Pregnant patients

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Ehlers-Danlos Syndrome; Patients with the diagnosis of Ehlers-Danlos syndrome
Controls; Patients/Subjects without the diagnosis of Ehlers-Danlos syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prevalence of OSA	up to 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Craniofacial phenotyping	up to 12 months
Aortic diameter	up to 12 months

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: University Children's Hospital, Zurich; Ehlers-Danlos Network, Switzerland
• Investigators: Principal Investigator: Malcolm Kohler, Prof. MD, University of Zurich

Publications and helpful links

General Publications

• Gaisl T, Giunta C, Bratton DJ, Sutherland K, Schlatzer C, Sievi N, Franzen D, Cistulli PA, Rohrbach M, Kohler M. Obstructive sleep apnoea and quality of life in Ehlers-Danlos syndrome: a parallel cohort study. Thorax. 2017 Aug;72(8):729-735. doi: 10.1136/thoraxjnl-2016-209560. Epub 2017 Jan 10.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: April 27, 2015
• First Submitted That Met QC Criteria: April 30, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Estimate): December 11, 2015
• Last Update Submitted That Met QC Criteria: December 10, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Prevalence; Obstructive Sleep Apnea; Aortic Aneurysm; Ehlers-Danlos Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Skin Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Signs and Symptoms, Respiratory; Skin Abnormalities; Collagen Diseases; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Syndrome; Apnea; Ehlers-Danlos Syndrome
• Other Study ID Numbers: KEK-ZH-Nr. 2015-0144