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Mutations in a gene called PHOX2B cause CCHS. The PHOX2B gene provides instructions for making a protein that is important during development before birth. The PHOX2B protein helps support the formation of nerve cells (neurons) and regulates the process by which the neurons mature to carry out specific functions (differentiation). The protein is active in the neural crest, which is a group of cells in the early embryo that give rise to many tissues and organs. Neural crest cells migrate to form parts of the autonomic nervous system, many tissues in the face and skull, and other tissue and cell types.

PHOX2B gene mutations that cause CCHS are believed to interfere with the PHOX2B protein's role in supporting neuron formation and differentiation, especially in the autonomic nervous system. As a result, bodily functions that are controlled by this system, including regulation of breathing, heart rate, blood pressure, and body temperature, are inconsistent in CCHS.

MedlinePlus Genetics: Causes

","key":"forms","title":"What causes Congenital central hypoventilation syndrome?"},{"bodyHtml":"

Symptoms of CCHS usually become apparent shortly after birth when affected infants hypoventilate upon falling asleep. In these infants, a lack of oxygen in the blood often causes a bluish appearance of the skin or lips (cyanosis). In some milder cases, CCHS may not become apparent until later in life.

In addition to the breathing problem, people with CCHS may have difficulty regulating their heart rate and blood pressure, for example, in response to exercise or changes in body position. They also have decreased perception of pain, low body temperature, and occasional episodes of heavy sweating.

People with CCHS may have additional problems affecting the nervous system. About 20 percent of people with CCHS have abnormalities in the nerves that control the digestive tract (Hirschsprung disease), resulting in severe constipation, intestinal blockage, and enlargement of the colon. (Some researchers refer to the combination of CCHS and Hirschsprung disease as Haddad syndrome.) Some affected individuals develop learning difficulties or other neurological problems. People with CCHS are also at increased risk of developing certain tumors of the nervous system called neuroblastomas, ganglioneuromas, and ganglioneuroblastomas.

Additionally, individuals with CCHS usually have eye abnormalities, including a decreased response of the pupils to light. People with CCHS, especially children, may have a characteristic appearance with a short, wide, somewhat flattened face often described as "box-shaped."

In CCHS, life expectancy and the extent of any intellectual disabilities depend on the severity of the disorder, timing of the diagnosis, and the success of treatment.

Source: MedlinePlus Genetics

","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"congenital-central-hypoventilation-syndrome","sourceDocuments":[{"name":"Congenital central hypoventilation syndrome","reviewed":"2008-09","sections":{"causes":{"fetchedAt":"2026-10-20T20:20:34.111737+00:00","label":"Causes","pageSha256":"74840acb92eded7a59238866452cf9f90da6d32891fc6db8d36aedd3888d5088","sourceUrl":"https://medlineplus.gov/genetics/condition/congenital-central-hypoventilation-syndrome/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/congenital-central-hypoventilation-syndrome"}],"sourceNote":"MedlinePlus descriptions and Causes; original HPO annotations.","takeawayHtml":"Cause explanations are from MedlinePlus Genetics. Feature values below retain their original sources and patient groups.","title":"Congenital central hypoventilation syndrome"},"schemaVersion":1}