Congenital central alveolar hypoventilation usually manifests at birth with shallow, erratic, or absent breathing. This disorder can also manifest during infancy, childhood, and adulthood because of variable penetrance of the PHOXZB mutation. Children with congenital central alveolar hypoventilation are more likely to have disorders of the auto- nomic nervous system, Hirschsprung’s disease, neural crest tumors, and characteristic box- shaped face (i.e., the face is short relative to its width).
Environmental. Ventilatory drive can be reduced in individuals using central nervous system depressants, including benzodiazepines, opiates, and alcohol.
Genetic and physiological. Idiopathic sleep-related hypoventilation is associated with reduced ventilatory drive due to a blunted chemoresponsiveness to C02 (reduced respi- ratory drive; i.e., “won’t breathe”), reﬂecting underlying neurological deficits in centers governing the control of ventilation. More commonly, sleep-related hypoventilation is co- morbid with another medical condition, such as a pulmonary disorder, a neuromuscular or chest wall disorder, or hypothyroidism, or with use of medications (e.g., benzodiaze- pines, opiates). In these conditions, the hypoventilation may be a consequence of in- creased work of breathing and / or impairment of respiratory muscle function (i.e., ”can’t breathe") or reduced respiratory drive (i.e., ”won’t breathe").
Neuromuscular disorders inﬂuence breathing through impairment of respiratory mo- tor innervation or respiratory muscle function. They include conditions such as amyo- trophic lateral sclerosis, spinal cord injury, diaphragmatic paralysis, myasthenia gravis,
Lambert-Eaton syndrome, toxic or metabolic myopathies, postpolio syndrome, and Char- cot-Marie-Tooth syndrome.
Congenital central alveolar hypoventilation is a genetic disorder attributable to muta- tions of PHOXZB, a gene that is crucial for the development of the embryonic autonomic nervous system and neural crest derivatives. Children with congenital central alveolar hy- poventilation show blunted ventilatory responses to hypercapnia, especially in non—rapid eye movement sleep.
Gender distributions for sleep-related hypoventilation occurring in association with co- morbid conditions reﬂect the gender distributions of the comorbid conditions. For exam- ple, COPD is more frequently present in males and with increasing age.
Sleep-related hypoventilation is diagnosed using polysomnography showing sleep-related hypoxemia and hypercapnia that is not better explained by another breathing-related sleep disorder. The documentation of increased arterial pCOz levels to greater than 55 mmHg 50 mmHg) during sleep in comparison to awake supine values, for 10 minutes or longer, is the gold standard for diagnosis. However, obtaining arterial blood gas determinations dur- ing sleep is impractical, and non-invasive measures of pC02 have not been adequately val- idated during sleep and are not widely used during polysomnography in adults. Prolonged and sustained decreases in oxygen saturation (oxygen saturation of less than 90% for more than 5 minutes with a nadir of at least 85%, or oxygen saturation of less than 90% for at least 30% of sleep time) in the absence of evidence of upper airway obstruction are often used as an indication of sleep-related hypoventilation; however, this finding is not specific, as there are other potential causes of hypoxemia, such as that due to lung disease.