TY - JOUR T1 - Systemic oxidative stress in the Congenital Central Hypoventilation Syndrome JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01497-2018 SP - 1801497 AU - Donatella Degl'Innocenti AU - Matteo Becatti AU - Marta Peruzzi AU - Claudia Fiorillo AU - Matteo Ramazzotti AU - Niccolò Nassi AU - Cinzia Arzilli AU - Raffaele Piumelli Y1 - 2018/01/01 UR - http://erj.ersjournals.com/content/early/2018/09/06/13993003.01497-2018.abstract N2 - The Congenital Central Hypoventilation Syndrome (CCHS), also known as Ondine's curse, is a rare disorder characterised by severe hypoventilation during sleep and autonomic dysregulation [1, 2]. The incidence of CCHS is about 1/200 000 live births. In more than 90% of cases, polyalanine repeat expansion (PolyALA) mutations are present in the paired-like homeobox PHOX-2B gene, although a frameshift variant (FS) may also be found [3]. The PHOX-2B gene encodes a highly conserved homeobox domain transcription factor which plays a regulatory role in the differentiation of the motor neuron and the serotonergic neuronal fate in the development of the central nervous system [4]. The hallmark of CCHS is the “forgotten breathing”, which implies the need for life-long mechanical ventilation during sleep. However, in more severe cases characterised by global hypoventilation, mechanical ventilation must also be extended during wakefulness. Ventilatory support may be provided by tracheostomy and assisted ventilation, non-invasive ventilation, or diaphragm pacemakers. Severe respiratory depression typically arises at birth, but in milder cases, CCHS may be diagnosed later on in childhood or adulthood (later-onset CCHS) [1, 2]. The clue to the respiratory defect is a reduced response to hypercapnia and hypoxemia depending on the malfunctioning of brainstem areas such as the retrotrapezoid nucleus, the parafacial respiratory group and the pre-Bötzinger complex which are involved in the chemosensory drive to breathe [5–7].FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Becatti has nothing to disclose.Conflict of interest: Dr. Peruzzi has nothing to disclose.Conflict of interest: Dr. Fiorillo has nothing to disclose.Conflict of interest: Dr. Ramazzotti has nothing to disclose.Conflict of interest: Dr. Nassi has nothing to disclose.Conflict of interest: Dr. Arzilli has nothing to disclose.Conflict of interest: Dr. Piumelli has nothing to disclose.Conflict of interest: Dr. Degl'Innocenti has nothing to disclose. ER -