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.

Keywords: CCHS; PHOX2B; congenital central hypoventilation syndrome; diaphragm pacing; home mechanical ventilation.

Figure 1

The respiratory balance. Notes: (A) In order to sustain adequate ventilation, ventilatory muscle power and central respiratory drive need to be sufficient to overcome the respiratory load. Normally, this balance is tipped to the right, indicating adequate ventilation. (B) In CCHS, central respiratory drive is decreased, and thus it is inadequate to overcome the respiratory load. This balance is tipped to the left, and respiratory failure results. Abbreviation: CCHS, congenital central hypoventilation syndrome.

Figure 2

Diaphragm pacing. Notes: A phrenic nerve electrode is surgically implanted. It is connected by a lead wire to a receiver implanted subcutaneously in the abdomen. A battery operated transmitter transmits electrical energy, via an antenna taped on the skin over the receiver, to the receiver. The receiver converts this to a standard electrical current, which causes contraction of the diaphragm. (Figure by Bill Franz.)