Congenital central hypoventilation syndrome

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Other Names:

CCHS; Idiopathic congenital central alveolar hypoventilation; Congenital failure of autonomic control; CCHS; Idiopathic congenital central alveolar hypoventilation; Congenital failure of autonomic control; Primary alveolar hypoventilation; Congenital Ondine curse; Ondine's curse (formerly); Ondine curse (formerly) See More

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

Congenital central hypoventilation syndrome (CCHS) is a disorder of the autonomic nervous system that affects breathing. It causes a person to hypoventilate (especially during sleep), resulting in a shortage of oxygen and a buildup of carbon dioxide in the blood. It have two forms of presentation, a classic form that usually begin shortly after birth in newborns, and a milder later-onset presentaition in toddlers, children and adults. Affected infants hypoventilate upon falling asleep and exhibit a bluish appearance of the skin or lips (cyanosis). Other features may include difficulty regulating heart rate and blood pressure; decreased perception of pain; low body temperature; sporadic profuse sweating; Hirschsprung disease; constipation; learning difficulties; eye abnormalities; and a characteristic facial appearance (having a short, wide, somewhat flattened face). They can also have tumors of neural crest origin, such as neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. The later-onset form is milder, and some cases may present as infants and children who die suddenly and unexpectedly (“SIDS” and “sudden unexplained death of childhood [SUDC]”).^[1]

CCHS is caused by a variation (mutation) in the PHOX2B gene and is inherited in an autosomal dominant manner. However, over 90% of cases are due to a new mutation in the affected person and are not inherited from a parent. Diagnosis is made with the clinical symptoms and the genetic test showing the variation in the PHOX2B gene. Treatment typically includes mechanical ventilation or use of a diaphragm pacemaker.^[2]^[1] People who have been diagnosed as newborns and adequately ventilated throughout childhood may reach the age of 20 to 30 years, and can live independently. In the later-onset form, people who were diagnosed when they were 20 years or older have now reached the age of 30 to 55 years.^[1]

Last updated: 3/20/2018

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Respiratory insufficiency	Respiratory impairment	0002093
5%-29% of people have these symptoms
Aganglionic megacolon	Enlarged colon lacking nerve cells	0002251
Cognitive impairment	Abnormality of cognition Cognitive abnormality Cognitive defects Cognitive deficits Intellectual impairment Mental impairment [ more ]	0100543
Ganglioneuroblastoma		0006747
Ganglioneuroma		0003005
Muscular hypotonia	Low or weak muscle tone	0001252
Seizure		0001250
Percent of people who have these symptoms is not available through HPO
Abnormality of temperature regulation	Poor temperature regulation	0004370
Abnormality of the cardiovascular system	Cardiovascular abnormality	0001626
Abnormality of the mouth	Abnormal mouth	0000153
Apnea		0002104
Autosomal dominant inheritance		0000006
Central hypoventilation		0007110
Constipation		0002019
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Hypercapnia	High blood carbon dioxide level	0012416
Hyperhidrosis	Excessive sweating Increased sweating Profuse sweating Sweating Sweating profusely Sweating, increased [ more ]	0000975
Hypoventilation	Slow breathing Under breathing [ more ]	0002791
Hypoxemia	Low blood oxygen level	0012418
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Posteriorly rotated ears	Ears rotated toward back of head	0000358

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Last updated: 1/1/2021

Do you have updated information on this disease? We want to hear from you.

Inheritance Inheritance

Congenital central hypoventilation syndrome (CCHS) is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

The genetics of CCHS can be complex. Most people with CCHS have a new (de novo) mutation in the responsible gene (the PHOX2B gene). De novo mutations occur for the first time in the affected person and are not inherited from a parent. Some people with CCHS have a parent with the condition, and inherit the mutation from that parent.

In some cases, an asymptomatic parent of a person with symptoms has a PHOX2B mutation in some of their germ cells (egg or sperm cells, not body cells). This is called germline mosaicism. Some of these parents also have a PHOX2B mutation in some of their body cells. This is called somatic mosaicism. Germline mosaicism with or without somatic mosaicism is present in about 25% of asymptomatic parents of people with CCHS.

Parents with mosaicism should have a comprehensive assessment to determine if any features of CCHS are present. It is also recommended that parents of a person with a presumed de novo mutation have genetic testing for the presence of the mutation, including testing that detects mosaicism at low levels.^[1]

Last updated: 3/20/2018

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Congenital central hypoventilation syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Congenital central hypoventilation syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Congenital central hypoventilation syndrome:
International CCHS REDCap Registry

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Sleep Association
110 W. Ninth Street, Suite 826
Wilmington, DE 19801
Fax: 940-234-3357
E-mail: http://www.sleepassociation.org/index.php?p=contactus
Website: http://www.sleepassociation.org/
Congenital Central Hypoventilation Syndrome (CCHS) Family Support Network
E-mail: vanderlaanm@hartwick.edu
Website: http://www.cchsnetwork.org/

Organizations Providing General Support

International Foundation for Functional Gastrointestinal Disorders (IFFGD)
3015 Dunes West Blvd. Suite 512
Mount Pleasant, SC 29466
Telephone: +1-414-964-1799
Website: https://iffgd.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Congenital central hypoventilation syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Congenital central hypoventilation syndrome. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Debra E Weese-Mayer, Mary L Marazita, Casey M Rand, and Elizabeth M Berry-Kravis. Congenital Central Hypoventilation Syndrome. GeneReviews. January 30, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1427/.
Congenital central hypoventilation syndrome. Genetics Home Reference. September 2008; http://www.ghr.nlm.nih.gov/condition/congenital-central-hypoventilation-syndrome.

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