Congenital central hypoventilation syndrome

Title

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. Symptoms usually begin shortly after birth. 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). CCHS is caused by a 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. Treatment typically includes mechanical ventilation or use of a diaphragm pacemaker.^[1]^[2]

Last updated: 1/12/2016

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Respiratory insufficiency	Very frequent (present in 80%-99% of cases)
Aganglionic megacolon	Occasional (present in 5%-29% of cases)
Cognitive impairment	Occasional (present in 5%-29% of cases)
Ganglioneuroblastoma	Occasional (present in 5%-29% of cases)
Ganglioneuroma	Occasional (present in 5%-29% of cases)
Muscular hypotonia	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Abnormality of temperature regulation	-
Abnormality of the cardiovascular system	-
Abnormality of the mouth	-
Autosomal dominant inheritance	-
Central hypoventilation	-
Constipation	-
Downslanted palpebral fissures	-
Feeding difficulties	-
Hyperhidrosis	-
Low-set ears	-
Posteriorly rotated ears	-

Last updated: 9/1/2017

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.^[2]

Last updated: 1/12/2016

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

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.
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.

Do you have updated information on this condition? Let us know.

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 studying or have studied 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.

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/
International Foundation for Functional Gastrointestinal Disorders (IFFGD)
PO Box 170864
Milwaukee, WI 53217
Toll-free: 888-964-2001
Telephone: 414-964-1799
Fax: 414-964-7176
E-mail: iffgd@iffgd.org
Website: http://iffgd.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

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.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

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. Submit a new question

If you have a mutation in one copy of the PHOX2B gene, does that mean you definitely have some degree of the disease, or that you may have or may develop the disease? See answer
If a person with congenital central hypoventilation syndrome has a child, what are the odds that the child will need a tracheotomy? See answer

Have a question? Contact a GARD Information Specialist.

References References

Congenital central hypoventilation syndrome. Genetics Home Reference. September 2008; http://www.ghr.nlm.nih.gov/condition/congenital-central-hypoventilation-syndrome.
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/.

Do you know of a review article? Send us your suggestions.