Aoi Hino1, Jiro Terada1, Hajime Kasai1, Hikaru Shojima2, Keiko Ohgino3, Ayako Sasaki4, Kiyoshi Hayasaka4,5, Koichiro Tatsumi1. 1. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan. 2. School of Medicine, Chiba University, Chiba, Japan. 3. Department of Respiratory Medicine, Kawasaki Municipal Hospital, Kawasaki City, Japan. 4. Department of Pediatrics, Yamagata University School of Medicine, Yamagata City, Japan. 5. Department of Pediatrics, Miyukikai Hospital, Kaminoyama, Japan.
Abstract
STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is caused by the paired-like homeobox 2B (PHOX2B) mutation and predominantly diagnosed during the neonatal period. Although late-onset CCHS and 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 late-onset 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 late-onset 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 and required some chronic ventilatory support at least during sleep, including portable positive pressure ventilator via tracheostomy or noninvasive positive pressure ventilation. In these patients with ventilatory support during sleep, sudden death or poor prognosis was 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 polyalanine repeat mutations 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.
STUDY OBJECTIVES:Congenital central hypoventilation syndrome (CCHS) is caused by the paired-like homeobox 2B (PHOX2B) mutation and predominantly diagnosed during the neonatal period. Although late-onset CCHS and 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 late-onset 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 late-onset 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 and required some chronic ventilatory support at least during sleep, including portable positive pressure ventilator via tracheostomy or noninvasive positive pressure ventilation. In these patients with ventilatory support during sleep, sudden death or poor prognosis was 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 polyalanine repeat mutations 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.
Authors: Nick A Antic; Beth A Malow; Neale Lange; R Doug McEvoy; Amy L Olson; Peter Turkington; Wolfram Windisch; Martin Samuels; Cathy A Stevens; Elizabeth M Berry-Kravis; Debra E Weese-Mayer Journal: Am J Respir Crit Care Med Date: 2006-07-27 Impact factor: 21.405
Authors: K J Low; A R Turnbull; K R Smith; T N Hilliard; L J Hole; D J Meecham Jones; M M Williams; A Donaldson Journal: Pediatr Pulmonol Date: 2014-05-05
Authors: Debra E Weese-Mayer; Elizabeth M Berry-Kravis; Isabella Ceccherini; Thomas G Keens; Darius A Loghmanee; Ha Trang Journal: Am J Respir Crit Care Med Date: 2010-03-15 Impact factor: 21.405
Authors: Debra E Weese-Mayer; Casey M Rand; Elizabeth M Berry-Kravis; Larry J Jennings; Darius A Loghmanee; Pallavi P Patwari; Isabella Ceccherini Journal: Pediatr Pulmonol Date: 2009-06
Authors: I Matera; T Bachetti; F Puppo; M Di Duca; F Morandi; G M Casiraghi; M R Cilio; R Hennekam; R Hofstra; J G Schöber; R Ravazzolo; G Ottonello; I Ceccherini Journal: J Med Genet Date: 2004-05 Impact factor: 6.318
Authors: Ajay S Kasi; Hong Li; Kelli-Lee Harford; Humphrey V Lam; Chad Mao; April M Landry; Sarah G Mitchell; Matthew S Clifton; Roberta M Leu Journal: J Multidiscip Healthc Date: 2022-03-08