Overview
Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse or Ondine syndrome, is a rare genetic disorder characterized by a failure of the autonomic control of breathing. Individuals with CCHS have inadequate or absent ventilatory responses to hypercapnia (elevated carbon dioxide) and hypoxemia (low oxygen), particularly during sleep. The condition results from mutations in the PHOX2B gene, which plays a critical role in the development of the autonomic nervous system. Most cases arise from polyalanine repeat expansion mutations in this gene, though frameshift and missense mutations also occur. CCHS primarily affects the respiratory system through impaired automatic breathing, but because PHOX2B is essential for broad autonomic nervous system development, the disorder can also involve the cardiovascular system (reduced heart rate variability, blood pressure dysregulation), the gastrointestinal system (Hirschsprung disease occurs in approximately 20% of patients), and the nervous system (risk of neural crest tumors such as neuroblastoma and ganglioneuroblastoma). Affected individuals typically present in the neonatal period with hypoventilation during sleep, though milder or later-onset forms have been described. Additional features may include ocular abnormalities such as altered pupillary response, profuse sweating, and decreased perception of pain. There is currently no cure for CCHS, and treatment is focused on lifelong ventilatory support to ensure adequate oxygenation and carbon dioxide removal, especially during sleep. Ventilatory options include tracheostomy with mechanical ventilation, bilevel positive airway pressure (BiPAP), negative pressure ventilation, or diaphragm pacing. Early diagnosis and consistent ventilatory management are critical to preventing the neurocognitive consequences of chronic hypoxemia. Patients require multidisciplinary follow-up including pulmonology, cardiology, gastroenterology, and oncology screening for neural crest-derived tumors, particularly in those with specific PHOX2B mutation types.
Clinical phenotype terms— hover any for plain English:
Autosomal dominant
Passed on from just one parent; each child has about a 50% chance of inheriting it
Neonatal
Begins at or shortly after birth (first 4 weeks)
FDA & Trial Timeline
10 eventsVA Office of Research and Development — PHASE4
Assistance Publique - Hôpitaux de Paris — NA
Assistance Publique - Hôpitaux de Paris
Shionogi Apnimed Sleep Science — PHASE2
Xiangya Hospital of Central South University
Ann & Robert H Lurie Children's Hospital of Chicago
Assistance Publique - Hôpitaux de Paris
VA Office of Research and Development — PHASE4
University Hospital, Grenoble
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
No FDA-approved treatments are currently listed for Congenital central hypoventilation syndrome.
3 clinical trialsare actively recruiting — trials can provide access to cutting-edge therapies.
View clinical trials →Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Financial Resources
1 resourcesPHYTONADIONE PHYTONADIONE
Dr.Reddy's Laboratories Inc
Travel Grants
No travel grants are currently matched to Congenital central hypoventilation syndrome.
Community
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Start the conversation →Latest news about Congenital central hypoventilation syndrome
Disease timeline:
New recruiting trial: Belgian Central Sleep Apnea REgistry
A new clinical trial is recruiting patients for Congenital central hypoventilation syndrome
New recruiting trial: Sleep Disordered Breathing and Multimorbidity: The Xiangya SDB Cohort Study
A new clinical trial is recruiting patients for Congenital central hypoventilation syndrome
New recruiting trial: Safety and Efficacy Study of Sivopixant, Acetazolamide and SASS-001 in Sleep Apnea
A new clinical trial is recruiting patients for Congenital central hypoventilation syndrome
New recruiting trial: Apnea, Stroke and Incident Cardiovascular Events
A new clinical trial is recruiting patients for Congenital central hypoventilation syndrome
New recruiting trial: Interface Selection for Adaptive Servo Ventilation
A new clinical trial is recruiting patients for Congenital central hypoventilation syndrome
New recruiting trial: Central Sleep Apnea : Physiologic Mechanisms to Inform Treatment
A new clinical trial is recruiting patients for Congenital central hypoventilation syndrome
New recruiting trial: CCHS Secure Health-hub Advancing Research Efforts (CCHS SHARE)
A new clinical trial is recruiting patients for Congenital central hypoventilation syndrome
Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Common questions about Congenital central hypoventilation syndrome
What is Congenital central hypoventilation syndrome?
Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse or Ondine syndrome, is a rare genetic disorder characterized by a failure of the autonomic control of breathing. Individuals with CCHS have inadequate or absent ventilatory responses to hypercapnia (elevated carbon dioxide) and hypoxemia (low oxygen), particularly during sleep. The condition results from mutations in the PHOX2B gene, which plays a critical role in the development of the autonomic nervous system. Most cases arise from polyalanine repeat expansion mutations in this gene, though frameshift and missen
How is Congenital central hypoventilation syndrome inherited?
Congenital central hypoventilation syndrome follows a autosomal dominant inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Congenital central hypoventilation syndrome typically begin?
Typical onset of Congenital central hypoventilation syndrome is neonatal. Age of onset can vary across affected individuals.
Are there clinical trials for Congenital central hypoventilation syndrome?
Yes — 3 recruiting clinical trials are currently listed for Congenital central hypoventilation syndrome on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.
Which specialists treat Congenital central hypoventilation syndrome?
25 specialists and care centers treating Congenital central hypoventilation syndrome are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.
What treatment and support options exist for Congenital central hypoventilation syndrome?
1 patient support program are currently tracked on UniteRare for Congenital central hypoventilation syndrome. See the treatments and support programs sections for copay assistance, eligibility, and contact details.