Patients with congenital central hypoventilation usually present in the neonatal period with cyanosis or apnea.
Although they may rarely present at a later age, symptoms usually are traceable to infancy. Patients with acquired central hypoventilation can present at any age. Patients may initially have nonspecific symptoms, such as lethargy, poor sleep, irritability, or morning headaches. These subtle signs are frequently overlooked, and it is not unusual for patients to be diagnosed only following catastrophic events, such as apparent life-threatening events (ALTE), seizures, or congestive heart failure resulting from cor pulmonale.

Patients with central hypoventilation do not have signs of respiratory distress or increased respiratory effort, even when severely hypoxemic or hypercapnic. The term “happy hypoxia” has been applied. This is in marked contrast to patients with respiratory failure secondary to pulmonary mechanical abnormalities, who will have subjective distress, tachypnea, and retractions. Patients with central hypoventilation usually have shallow, slow breathing rather than frank central apnea. The patient may be able to transiently breathe adequately voluntarily when instructed to do so.

The physical examination in children with central hypoventilation is usually normal. Growth failure or signs of pulmonary hypertension (such as an increased pulmonic component of the second heart sound) may be present. In children with secondary central hypoventilation, the underlying condition or associated neurologic abnormalities are usually evident.

Laboratory tests are necessary to (a) establish the presence of hypoventilation, and (b) investigate the cause. The presence of hypoventilation is established by arterial blood gas analysis. However, a single arterial blood gas does not reflect adequately the patient’s ventilation, particularly during sleep. Thus, serial blood gas monitoring via an arterial line, or continuous noninvasive capnometry and oximetry monitoring during polysomnography, is preferable. It is essential to assess gas exchange during both wakefulness and sleep.

Potential diagnostic tests are shown in Box 239.2; the choice of tests must be individualized for each patient. Pulmonary and neuromuscular causes of hypoventilation must be excluded. In particular, isolated diaphragmatic paralysis should be excluded. The hypoventilation can be assumed to be central in origin if tests of pulmonary function and ventilatory muscle strength are normal, and metabolic abnormalities are excluded. Magnetic resonance imaging of the brainstem is recommended for all patients with central hypoventilation of undetermined etiology. The diagnosis of congenital central hypoventilation syndrome (CCHS) is made primarily by exclusion, according to the following criteria: (a) persistent hypoventilation during sleep (PCO₂ consistently greater than 60 mm Hg during sleep), (b) onset of symptoms from birth or early infancy, and (c) absence of primary pulmonary, cardiac, central nervous system, neuromuscular, or metabolic dysfunction. Recently, generic confirmation become available.