Central hypoventilation syndrome

Not to be confused with Central sleep apnea.

Central Hypoventilation Syndrome

Central Hypoventilation Syndrome (CHS) is a sleep-related breathing disorder that causes ineffective breathing, apnea, or respiratory arrest during sleep, and in severe cases, during wakefulness. CHS can either be congenital (CCHS) or acquired (ACHS) later in life. The condition can be fatal if untreated. CCHS was once known as Ondine's curse.

ACHS can develop as a result of severe injury or trauma to the brain or brainstem. Congenital cases are very rare and involve a failure of autonomic control of breathing. The diagnosis may be delayed due to variations in the severity of the manifestations or lack of awareness in the medical community, particularly in milder cases. In all cases, episodes of apnea occur in sleep, but in a few patients, at the most severe end of the spectrum, apnea also occurs while awake.

Signs and Symptoms

CHS is associated with respiratory arrests during sleep and, in some cases, to neuroblastoma (tumors of the sympathetic ganglia), Hirschsprung disease (partial agenesis of the enteric nervous system), dysphagia (difficulty swallowing), and anomalies of the pupilla. Other symptoms include darkening of skin color from inadequate amounts of oxygen, drowsiness, fatigue, headaches, and an inability to sleep at night. Patients with CHS also have a sensitivity to sedatives and narcotics, which makes respiration even more difficult. A low concentration of oxygen in the red blood cells also may cause hypoxia-induced pulmonary vasoconstriction and pulmonary hypertension, culminating in cor pulmonale or a failure of the right side of the heart. Associated complications may also include gastro-esophageal reflux, ophthalmologic issues, seizures, recurrent pneumonia, developmental delays, learning disabilities, episodes of fainting, and temperature disregulation.

Causes

CHS is exhibited typically as a congenital disorder, but in rare circumstances, can also result from severe brain or spinal trauma or injury or due to particular neurodegenerative conditions such as Parkinson's disease, multiple system atrophy, or multiple sclerosis. Medical investigation of patients with this syndrome has led to a deeper understanding of how the body and brain regulate breathing on a molecular level. PHOX2B, a transcription factor involved in the development of neurons, can be associated with this condition. This homeobox gene is important for the normal development of the autonomic nervous system.

Diagnosis

Children with CCHS develop life-threatening episodes of apnea with cyanosis, usually in the first months of life. Medical evaluation excludes lesions of the brain, heart, and lungs but demonstrates impaired responses to build-up of carbon dioxide (hypercapnia) and decreases of oxygen in the circulation (hypoxia), the two strongest stimuli to increase breathing rate.

Polysomnography shows that hypoventilation is most marked during slow-wave sleep. In the most severe cases, hypoventilation is present during other nonrapid eye movement sleep stages and even wakefulness. A subset of CCHS patients are at very high risk for developing malignant neural crest-derived tumors, such as neuroblastoma.

The sequence of PHOX2B reveals mutations in 91% of the cases.

Treatment

People generally require tracheostomy and lifetime mechanical ventilation on a ventilator in order to survive. However, it has now been shown that biphasic cuirass ventilation can effectively be used without the need for a tracheotomy. Other potential treatments for CHS include oxygen therapy and medicine for stimulating the respiratory system. Currently, problems arise with the extended use of ventilators, including fatal infections and pneumonia.

Prognosis

Most people with CCHS (unless they have the Late Onset form) do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is diaphragm pacing.

History

CCHS was first described in 1962 by Severinghaus and Mitchell in three patients following surgery to the upper cervical spinal cord and brainstem.

Etymology

Its name is a reference to the story of Ondine and Hans, characters in Ondine, a 1938 play by Jean Giraudoux based on traditions tracing back through Undine (a novella of 1811) to earlier European folk tales. The water-spirit Ondine tells her future husband Hans, whom she had just met, that "I shall be the shoes of your feet ... I shall be the breath of your lungs". Ondine makes a pact with her uncle the King of the Ondines that if Hans ever deceives her he will die. After their honeymoon, Hans is reunited with his first love Princess Bertha and Ondine leaves Hans only to be captured by a fisherman six months later. On meeting Ondine again on the day of his wedding to Bertha, Hans tells her that "all the things my body once did by itself, it does now only by special order ... A single moment of inattention and I forget to breathe". Hans and Ondine kiss, after which he dies.

See Also

• Our Curse, an Oscar-nominated 2013 short documentary film about a child with Ondine's curse

Classification	ICD-10: G47.35 ICD-9-CM: 327.25 OMIM: 209880 MeSH: D020182 DiseasesDB: 32976
External resources	MedlinePlus: 000078 eMedicine: article/1002927 GeneReviews: Congenital central hypoventilation syndrome

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