Central hypoventilation syndrome (CHS) is a rare disorder, which can be both congenital [1] and acquired [2]. Congenital central hypoventilation syndrome (CCHS) is caused by chromosomal mutations in the PHOX2B gene on chromosome 4p12 [3]. The non-congenital or acquired form of CHS may be due to brain stem tumor, infarct, or edema [4]. As the acquired form of this disease is quite rare, the main focus of this article will be the congenital form of CHS. The main characteristic of CCHS is small tidal volumes and monotonous respiratory rates while awake and asleep, with more profound alveolar hypoventilation during sleep [5]. Due to hypoventilation, these patients develop hypercapnia and hypoxemia but lack the normal ventilatory responses to overcome these conditions while asleep [6]. However, while awake, they do have the ability to consciously alter the rate and depth of breathing. While sleeping, these children exhibit shallow respirations interspersed with periods of apnea most commonly during non-REM sleep [7]. Diagnosis is primarily made by excluding a primary lung, cardiovascular, neuromuscular or brainstem disease that accounts for the clinical picture [8]. CCHS is a lifelong condition and will require some form of ventilatory support throughout life, either positive pressure ventilation via tracheostomy or nasal mask. Other forms of long-term management include negative pressure ventilation and diaphragmatic pacing. CCHS usually manifests itself in the newborn period with episodes of cyanosis and apnea, and most infants will require mechanical ventilation immediately after birth [6]. CCHS can also present in later infancy, childhood and even adulthood and is then termed as Late Onset CCHS (LO-CCHS) [9]. The diagnosis of LO-CCHS should be considered if there is hypoventilation, cyanosis or seizures after administration of CNS depressants or anesthetics, after pulmonary infection, or during treatment of obstructive sleep apnea. LO-CCHS reflects the variable penetrance of PHOX2B mutations [10]. As the PHOX2B gene plays a role in neural crest cell migration, this disease is also linked with other neurocristopathies such as Hirschsprung disease caused by an absence of segmental colonic ganglia. 

Hirschsprung disease is present in approximately 20% of patients with CCHS, a combination referred to as Haddad syndrome [10]. Additionally, CCHS may be associated with neural crest-derived tumors such as neuroblastoma, ganglioneuroblastoma, and ganglioneuroma, which occur in 5–10% of affected individuals [7]. 

Patients with CCHS also commonly experience a range of symptoms related to autonomic nervous system dysfunction (ANSD). These include bradycardia and transient abrupt asystoles, decreased pupillary light response, esophageal dysmotility, breath holding spells, reduced body temperature, sporadic profuse sweating and lack of physiological responses to the challenges of exercise and environmental stressors [11].