Adult cases of late-onset CCHS and PHOX2B-mutation carriers: an additional case report and pooled analysis.

STUDY OBJECTIVES Congenital central hypoventilation syndrome (CCHS) is caused by the PHOX2B mutation and predominantly diagnosed during the neonatal period. Although late-onset (LO)-CCHS and paired-like homeobox 2B (PHOX2B) mutation carriers have been reported, the features of these disease states in adults remain uncertain. This study aimed to identify the characteristics of adult-onset CCHS and PHOX2B-mutation carriers in adult. METHODS We mainly searched the PubMed/Medline and Cochrane Databases and classified our target patients into 2 groups: group A, symptomatically diagnosed with LO-CCHS in adulthood; group B, adult PHOX2B-mutation carriers. Then, clinical characteristics including the onset, treatment, long-term course, and pattern of the PHOX2B mutation in both groups were analyzed. Additionally, a new adult-case of LO-CCHS was added to the analysis. RESULTS Group A was comprised of 12 patients. The onset triggers of illness included a history of respiratory compromise following general anesthesia and respiratory tract infections. All patients in Group A had 20/25 polyalanine repeat mutations (PARM) and required some chronic ventilatory support at least during sleep, including portable positive pressure ventilator via tracheostomy or non-invasive positive pressure ventilation (NPPV). In these patients with ventilatory support during sleep, sudden death or poor prognosis were not reported. Group B was comprised of 33 adults from 24 families with PHOX2B-mutations. Nine patients in Group B were confirmed with the diagnosis of CCHS. Although PARM 20/25 represented the most common gene mutation, diverse mutations, including mosaicism, were observed. Hypoventilation of several cases in group B were underdiagnosed by overnight polysomnography without monitoring for CO₂. CONCLUSION Alveolar hypoventilation with unknown origin can be caused by the PHOX2B mutation even in adult cases. Both the identification of the PHOX2B-mutation and the incorporation of capnography in polysomnography are important for adult cases with unexplained alveolar hypoventilation or asymptomatic mutation carriers.