Congenital Central Hypoventilation Syndrome Treatment & Management

Updated: Apr 21, 2021
  • Author: Amy Brown, MD, MS; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
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Approach Considerations

There is no cure or gene therapy for congenital central hypoventilation syndrome (CCHS). Treatment is entirely supportive and is based on assessment of respiratory impairment, cardiac dysfunction, and gastrointestinal dysfunction, as well as surveillance for underlying oncologic manifestations.


Medical Care

Congenital central hypoventilation syndrome (CCHS) is a lifelong condition. A multidisciplinary approach to provide for comprehensive care and support of every child is needed.

General measures

CCHS patients require biannual then annual evaluation to assess their ventilatory needs not only while awake and in all stages of sleep, but also with varying levels of activity while awake. Ventilatory response to different physiologic challenges while awake and asleep should also be assessed. Other testing that should be done on a semi-annual basis until age 3 and an annual basis after includes 72-hour Holter monitoring, echocardiography, assessment of autonomic nervous system dysregulation, formal neurocognitive assessment, polysomnography, and blood work (hemoglobin, hematocrit, reticulocyte count, and bicarbonate.) Surveillance based on mutation type is also recommended. Patients with long PARM mutations (28 repeats and longer) and NPARM mutations require chest imaging, abdominal imaging and urine catecholamine monitoring every 3 months until age 2 and every 6 months until age 7 to rule out neuroblastomas and other neural crest cell tumors. [1]

Ophthalmoplegia and other ocular anomalies have long been recognized to be occasionally present; therefore, a thorough and periodic (ie, every year) ophthalmologic evaluation is necessary

Reports of dysregulation in glucose homeostasis in patients with CCHS have been published. Patients can have asymptomatic episodes of hypoglycemia, which are thought to be due to hyperinsulinism. An observational study in France found that half the patients had either abnormal glucose values (mostly postprandial hyperglycemia) or impaired glucose tolerance. [31, 32] Autonomic nervous system abnormalities can affect glucose concentrations (either hyperglycemia or hypoglycemia) in CCHS; therefore, glucose monitoring should be considered.

Gastrointestinal problems

Infants with CCHS may have significant hypotonia and temporary feeding difficulties. In addition, moderate-to-severe gastroesophageal reflux is frequently present and may require early administration of prokinetic agents and antireflux medications, especially in patients with hypotonia, temporary feeding difficulties, and gastroesophageal reflux. Surgical procedures (such as percutaneous gastrostomy tube feeding insertion, antireflux surgical procedures, or both) may be necessary if these problems are severe or persistent.

For patients with Hirschsprung disease, surgical intervention and, sometimes, colostomy to relieve the distal intestinal obstruction, may be required. For patients with a history of constipation, consider barium enema, manometry, or full-thickness rectal biopsy.


Pharmacologic approaches to enhance the respiratory stability and promote eucapnia in patients with CCHS have been unsuccessful. Therefore, respiratory stimulants have no current role in the treatment of CCHS. [20]

Case reports have described progesterone, a known respiratory stimulus, establishing ventilatory response to carbon dioxide in patients with CCHS. [33] In vitro studies have described the use of 17-AAG and curcumin, used for treatments of tumors, as effective in promoting the clearance of mutant PHOX2B aggregates and restoring the activity of PHOX2B with the largest polyalanine expansion. [34]

Invasive mechanical ventilatory support

To date, most centers that provide long-term home care for children with CCHS use positive-pressure ventilation through a permanent tracheostomy. Depending on the severity of alveolar hypoventilation, some patients only need ventilatory support at night, while others may need it around the clock.

Ventilators should be used in the spontaneous intermittent mandatory ventilation (SIMV) mode. Because an uncuffed tracheostomy should be used to minimize granuloma formation, ventilator settings should compensate for air leaks around the tracheotomy tube by increasing volume and peak airway pressure as necessary.

The recent availability of continuous-delivery compressors in home ventilators now permits domiciliary and ambulatory administration of ventilator modes traditionally reserved for intensive care units. Mildly hyperventilating patients with CCHS during their sleep to achieve PCO2 near 30-35 mm Hg is recommended. Mild nighttime hyperventilation results in better daytime spontaneous ventilation and gas exchange ("sprinting").

Noninvasive ventilatory support

Although there have been some favorable reports of negative-pressure ventilation (NPV) in CCHS patients, this modality is also cumbersome and requires significant equipment adjustments over time. In addition, NPV may be associated with upper airway obstruction during sleep in younger children with CCHS. In addition, NPV relies on the ability of chest wall movement; therefore, patients with chest wall deformity may not be good candidates for NPV.

Nasal mask ventilation has been proven to be a less invasive modality that is effective in patients with CCHS who are older than 7-8 years and who are nocturnally dependent on the ventilator. It is not only effective but is the preferred mode of ventilatory support by parents and patients, and even children who are established on other modes of ventilatory support can be successfully weaned onto mask ventilation within a short period. [35]

The transition of a children from invasive mechanical ventilation (IMV) to noninvasive mechanical ventilation (NMV) should be performed in a stepwise function. First, the identification of eligible patients, then the initiation of airway rehabilitation, weaning from IMV, trial with NIV, and finally decannulation. Only attempting NIV on patients who are stable at baseline is crucial. The following criteria has been proposed for eligibility to transition from IMV to NIV: (a) patient's normal consciousness state; (b) intact cough reflex and managing respiratory secretions; (c) need of suction of the trachea less than or equal to 1 time/day; (d) daytime tolerated tracheostomy capping; (e) IMV dependency only during sleep; (f) integrity of upper and lower airways on bronchoscopy assessment; (g) patient and family's motivation.  [36]

Diaphragm pacing

Daytime diaphragm pacing in children with CCHS provides greater mobility than mechanical ventilation. [37] Thus, candidates for diaphragm pacing are potentially ambulatory patients who require ventilatory support 24 h/d via tracheotomy and who do not exhibit significant ventilator-related lung damage. Diaphragm pacer settings must provide adequate alveolar ventilation and oxygenation during rest and daily activities. Long-term outcome appears good, especially quality of life. [38]

Potential risks may be associated with surgical implantation and possible need for surgical revisions because of pacer malfunction. Diaphragm pacing requires increased level of fitness of the diaphragm. This is achieved by gradually increasing the length of time the child is paced. Most children can tolerate approximately 12-14 hours of pacing per day. Despite these limitations, most parental reports regarding diaphragm pacing are favorable. Development of a quadripolar electrode offers several advantages that primarily include greater durations of diaphragmatic pacer support at diminished risk of phrenic nerve damage, decreased diaphragmatic fatigue, and optimization of pacing requirements during exercise. Therefore, as equipment improves, the need to replace components is lessened.

Some families attempt diaphragmatic pacing during sleep to facilitate tracheal deaccannulation. Relying on diaphragmatic pacing as full life support during sleep requires extreme caution. Sleep endoscopy data from children with CCHS who use diagragmatic pacing reveals varying degrees of airway obstruction coupled with inadequate gas exchange in many cases. If parents and patients desire decannulation, sleep-state breathing may be better supported by noninvasive mask ventilation rather than diaphragmatic pacing in many cases.  [39]

Deciding on the most appropriate type of ventilatory support requires referral to specialized centers with personnel experienced in diaphragm pacing.

Medicolegal concerns

The major medicolegal situations that may develop primarily involve the delayed diagnosis of CCHS or the assignment of causal relationships between CCHS and any type of fetal exposure.

For example, legal issues may arise from the potential association between ingestion of any given medication or exposure to a particular environmental situation; however, no current evidence links a particular teratogen to CCHS. Thus, although the embryology of the neural crest is still actively researched and is clearly linked to CCHS, no associations between exposure to chemicals during a particular phase of pregnancy and ultimate development of CCHS are noted.

A more frequent, albeit less argumentative, issue involves the recognition and diagnosis of CCHS. Infants who develop apnea or apparent life-threatening events during early postnatal life could have a mild variant of the wide clinical spectrum of CCHS and ultimately die of sudden infant death syndrome (SIDS). Because the manifestations in cases of SIDS/CCHS are subtle, diagnosing CCHS and preventing SIDS would be impossible.

On the other side of the severity spectrum, multiple unsuccessful trials to wean mechanical ventilation in an otherwise full-term baby should raise the suspicion for central hypoventilation syndrome, either congenital or secondary to other conditions. Early recognition of the appropriate diagnostic entity using the diagnostic approach elaborated in Workup prevents unnecessary delays in tracheotomy and in the institution of mechanical ventilatory support using a home ventilator, thereby accelerating the discharge process and preventing iatrogenic complications (eg, self-extubation, acute and chronic tracheal injury) that arise from ventilatory support using an endotracheal tube.


Surgical Care

Tracheostomy may be indicated for ventilatory support. Colostomy is sometimes required when Hirschsprung disease is present. When feeding problems arise, particularly during infancy, gastrostomy tube placement with or without antireflux procedures may be required.

Usual postoperative follow-up care for these procedures is necessary but does not differ from the care needed by any other patient.

Diaphragmatic pacing should be considered in appropriate patients. Those patients that may be candidates are patients who are ventilator dependent only during sleep and without significant co-morbidities. [40]  Obesity seems to be an unfavorable co-morbid condition to successful diaphragmatic pacing.  



The diagnostic evaluation of patients with congenital central hypoventilation syndrome requires a multidisciplinary approach involving many specialists, such as the following:

  • Pulmonologist

  • Neurologist: Consultation with a pediatric neurologist is recommended in the evaluation of hypotonia or seizure activity; seizures can occur in some children with congenital central hypoventilation syndrome (CCHS) spontaneously or as a result of acute hypoxia. Nerve conduction studies, electromyography (EMG), muscle biopsy, auditory-evoked potentials, EEG, and imaging studies of the CNS may be necessary.

  • Cardiologist: Evaluation by a cardiologist is suggested to exclude any cardiac involvement.

  • Gastroenterologist: Evaluation by a gastroenterologist is suggested to rule out bowel hypomotility, to evaluate for gastroesophageal reflux, and to assist in management of Hirschsprung disease.

  • Hematologist: Evaluation by a hematologist is suggested in patients with a history of thrombosis or hypercoagulability.

  • Ear, nose, and throat (ENT) specialist: Evaluation by an otolaryngologist is suggested for tracheostomy evaluation, surgery, and regular postoperative and long-term care.

  • Social worker, speech therapist, respiratory therapist, and other healthcare specialists: Evaluation by these specialists is suggested to provide multidisciplinary care and follow-up.

  • Child behavior specialist: Periodic developmental assessment by a child behavior specialist is suggested.



Children with congenital central hypoventilation syndrome (CCHS) can lead active lives and are not restricted from any of the usual activities engaged in by healthy children. In water activities, such as swimming, special protective devices are required for the tracheostomy tube to prevent aspiration. Nevertheless, many children with CCHS participate in aquatic activities without any identifiable adverse consequence. Patients require close supervision by the parents or caretakers while swimming or while playing in swimming pools or similar situations. This is because these children do not sense air hunger while diving and can therefore become severely hypoxic underwater and lose consciousness.

Because of an absent or negligible respiratory drive, it is recommended that patients with CCHS monitor pulse oximetry and end-tidal carbon dioxide, particularly during asleep states, because they may develop profound hypoxemia and hypercarbia. [1]