Adult Identified with Congenital Central Hypoventilation Syndrome-Mutation in PHOX2b Gene and Late-Onset CHS

To the Editor.

In light of our recent review of the genetic basis for congenital central hypoventilation syndrome (CCHS) (1), we bring to your attention a 35-year-old adult recently identified as having had late-onset CHS and the CCHS-mutation in PHOX2b.

One year ago this patient presented with a history of snoring "for his whole life," nocturnal gasping, and "stopping breathing and turning blue." During polysomnography he had 46 obstructive events (38 hypopneas, 8 apneas), 16 central apneas, and an apnea-hypopnea index of 77 events/hour, with an Sa^sub O^sub 2^^ nadir of 65% in room air and 80% with supplemental oxygen. He temporarily responded to Bi-Pap with supplemental oxygen during sleep, but within 6 months was referred for uvulopalatopharyngoplasty. He was readmitted 48 hours after discharge with intermittent confusion, difficulty staying awake, and respiratory failure (awake arterial PCO^sub 2^ of 73 mm Hg). His admission hematocrit was 73%, body temperature was 35.5

On the basis of this remarkably late presentation of the alveolar hypoventilation component of CHS, we suggest that adult pulmonologists and intensivists consider the possibility of late-onset CHS, confirmable by PHOX2b assay, when caring for adults with hypercarbia of unknown etiology. From a scientific perspective, this case raises the possibility of a regulatory gene that modifies the expression or activity of PHOX2b, determining the severity of the autonomic dysregulation in late-onset CHS.