The hallmark of CCHS is reduced or shallow breathing due to dysregulation of the respiratory drive. In general, reduced and shallow breathing is most apparent in non–REM sleep, but breathing is also abnormal during REM sleep and wakefulness, although usually to a milder degree. Individuals with CCHS also cannot sense oxygen or carbon dioxide levels in their body, which results in discoloration of their skin and lips, indicating that oxygen levels in the body are low. Low oxygen levels can cause increased risk for organ damage, especially to the brain. Thus, it is important to optimize oxygenation and ventilation in these patients. Depending on the severity of CCHS, the degree of life-long ventilatory support can vary from sleep only to constant support.
Adequate ventilation is essential to ensure optimal growth and development of CCHS patients. Ventilation can be managed with a mechanical ventilator via tracheostomy or masks, or using phrenic pacemakers. Monitoring both oxygen saturations and CO2 using end-tidal capnography at home helps ensure adequate ventilation in all conditions (sleep, awake, during illness and growth spurts). The support of experienced at-home nursing care will help families continue functioning at home. Ventilatory needs vary greatly across mutations, and sometimes within the same mutation. Appropriate ventilation for each child is essential to ensure optimal developmental outcomes. Because of the CCHS patient’s inability to sense changes in CO2, as well as O2, supplemental oxygen alone is not adequate for treating the individual with CCHS, and can mask elevated CO2 levels when both are not monitored.
Cardiovascular system Cardiac asystoles (heart stops beating) have been noted in several PARM mutations, and should be monitored extensively and actively throughout CCHS patients’ lives. This can include, but not be limited to regular extended Holter monitoring, implantable loop recorders, etc. CCHS patients do not sense cardiac pauses and are often asymptomatic until a life-threatening event occurs (loss of consciousness, sudden death). Within the CCHS community, children across many PARM mutations have demonstrated need for cardiac pacemaker implantation, even at a young age.
Additional cardiovascular symptoms of CCHS include altered temperature regulation, altered heart rate variability, altered blood pressure regulation, and poor circulation that may only be apparent under stressors such as illness or surgery.
Digestive system Both PARM and NPARM CCHS patients can present with alterations in their digestive system. Mild symptoms can be reflux and poor upper GI motility. Other patients can present with Hirschsprung’s disease (HD). HD is more often present in NPARMs or higher PARM expansions. Reflux is often treated via medication, while poor upper GI motility may often be managed with therapy and altered diets. Surgical treatment is required for HD.
Ophthalmology Some children with CCHS have been identified with ophthalmological problems associated with CCHS. These include, strabismus, abnormal pupil dilation, the need to wear corrective lenses, as well as Marcus Gunn jaw-winking syndrome and absent or reduced depth perception. Management can range from corrective lenses, wearing sunglasses when outside to surgical procedures.
Endocrine system The endocrine system can be affected by mutations in the PHOX2B gene. The most commonly noted are growth hormone deficiency and congenital hyperinsulinemia.
Cancer Patients with CCHS can develop tumors of neural crest origin, such as ganglioneuromas, ganglioneurblastomas, and neuroblastomas. Treatment for these tumors involves surgery followed by chemotherapy, if needed.
The 2010 ATS Statement recommends that CCHS children with 20/29-20/33 PARM mutations as well as those with NPARMs should be screened at diagnosis of CCHS and with advancing age for neural crest tumors.