Congenital central hypoventilation syndrome: Diagnostic and management challenges

Abstract

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with failure of central control of breathing and of the autonomic nervous system function due to a mutation in the paired-like homeobox 2B (PHOX2B) gene. Affected patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxemia, and they do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis of CCHS must be confirmed with PHOX2B gene mutation. Generally, the PHOX2B mutation genotype can aid in anticipating the severity of the phenotype. They require ventilatory support for life. Home assisted ventilation options include positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and diaphragm pacing via phrenic nerve stimulation, but each strategy has its associated limitations and challenges. Since all the clinical manifestations of CCHS may not manifest at birth, periodic monitoring and early intervention are necessary to prevent complications and improve outcome. Life-threatening arrhythmias can manifest at different ages and a normal cardiac monitoring study does not exclude future occurrences leading to the dilemma of timing and frequency of cardiac rhythm monitoring and treatment. Given the rare incidence of CCHS, most health care professionals are not experienced with managing CCHS patients, particularly those with diaphragm pacers. With early diagnosis and advances in home mechanical ventilation and monitoring strategies, many CCHS children are surviving into adulthood presenting new challenges in their care.

The genetics of congenital central hypoventilation syndrome: clinical implications

“…As they mature, some infants may develop a normal pattern of adequate breathing while awake, allowing them to be off assisted ventilation for periods of time during wakefulness. 1 , 2 , 4 , 6 , 11 – 14 …”

“…Patients should be referred for comprehensive ophthalmology evaluation to identify abnormalities and provide intervention to prevent learning interference. 1 , 11 , 12 CCHS patients have been found to demonstrate developmental delay and neurocognitive deficits as early as preschool age indicating need for neurocognitive evaluation. 14 , 72 – 76 …”

“…The goal of treatment is to ensure adequate ventilation at all times, both while awake and during sleep to prevent morbidities secondary to untreated hypoxemia or hypercapnia and anticipatory management of associated autonomic dysfunction. 1 , 4 , 11 , 12 At our center, we recommend maintaining PetCO 2 ~35 mmHg and SpO 2 ≥95%. 11 , 12 It is essential to recognize that oxygen alone relieves the hypoxemia and cyanosis but would not address hypoventilation.…”

“… 1 , 4 , 11 , 12 At our center, we recommend maintaining PetCO 2 ~35 mmHg and SpO 2 ≥95%. 11 , 12 It is essential to recognize that oxygen alone relieves the hypoxemia and cyanosis but would not address hypoventilation. For those who are asymptomatic, it is important to remember that they are at risk for respiratory decompensation with stress, infections, or when undergoing procedures requiring sedation or anesthesia.…”

Ondine’s curse: the origin of the myth

“…Typically, this occurs during non-rapid eye movement sleep, when the ventilatory drive is controlled almost entirely by metabolic input; resulting in hypercapnia or hypoxemia 11 . Patients with congenital hypoventilation not only lack appropriate ventilatory responses to hypercapnia and hypoxia, but they also lack the sensations and physical symptoms of respiratory compromise such as dyspnea and discomfort 6,12,13 .…”