The paired-like homeobox 2B (PHOX2B) gene and respiratory control

Crawford, Mark W.

doi:10.1007/s12630-011-9591-6

Cited by 3 publications

(12 citation statements)

References 21 publications

(30 reference statements)

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“…El centro respiratorio esta formado por el grupo respiratorio dorsal (neuronas inspiratorias) y el grupo respiratorio ventral (neuronas inspiratorias y espiratorias), ambos incian, modulan y regulan la respiración (9,11,12). Otra área importante para el control del impulso ventilatorio, es el núcleo retrotrapezoide (RTN), ubicada en la superficie ventral de la médula, donde su actividad neuronal esta modulada por el CO 2 y el pH (3,8,13,14).…”

Section: Aspectos Fisiopatológicosunclassified

“…Diferentes mutaciones del gen PHOX2B conducen a diferentes grados y mecanismos de disfunción celular, que tienen implicaciones en la gravedad del fenotipo, los PARM más largos y NPARM resultarán en fenotipos clínicos graves (14,17,22) y enfermedad más leve en PARM cortos (4,13). Sin embargo, actualmente se reporta que los NPARM manifiestan un amplio espectro de fenotipos, algunos de los cuales pueden tener sólo hipoventilación leve, mientras que otros tienen una afectación intestinal extensa y necesidad de asistencia ventilatoria (AV) continua (20).…”

Section: Sindrome De Hipoventilación Central Congénita (Congenital Central Hypoventilation Syndrome -Cchs)unclassified

“…Fisiopatología.-Las mutaciones del gen PHOX2B reducen la sensibilidad al CO 2 en las neuronas donde se expresan (10,13,14). Estudios post mortem de los loci afectados, presentaron pérdida severa y selectiva de interneuronas medulares que expresan PHOX2B en el RTN y región parafacial de la médula rostral (14,15).…”

Section: Sindrome De Hipoventilación Central Congénita (Congenital Central Hypoventilation Syndrome -Cchs)unclassified

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Trastornos De Hipoventilación Central Del Sueño en Pediatría: Causas Poco Frecuentes

A¹,

S²

2021

Neumol Pediatr

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El síndrome de hipoventilación central congénita (CCHS) y síndrome de obesidad de inicio rápido con disfunción hipotalámica, hipoventilación y desregulación autonómica (ROHHAD), son causas poco comunes de hipoventilación durante el sueño en la población pediátrica. Este grupo de trastornos se caracterizan por ausencia o disminución en el control automático de la ventilación, sensibilidad disminuida de los quimioreceptores al CO2, provocando hipoventilación durante el sueño e incluso en vigilia, en los casos más severos. Por estas razones es importante diagnosticarlos y tratarlos oportunamente. El objetivo de esta revisión es proporcionar literatura actual y completa, para poder identificar, tratar y referir a éste grupo de niños tempranamente, y así disminuir las complicaciones y/o comorbilidades asociadas a corto y largo plazo, mejorando su calidad de vida

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Section: Aspectos Fisiopatológicosunclassified

Section: Sindrome De Hipoventilación Central Congénita (Congenital Central Hypoventilation Syndrome -Cchs)unclassified

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Trastornos De Hipoventilación Central Del Sueño en Pediatría: Causas Poco Frecuentes

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S²

2021

Neumol Pediatr

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“…At present, the cardiorespiratory effects of pediatric CCHS and ROHHAD patients undergoing lung isolation on both lungs during the same anesthetic has not been well described. There are individual and compilations of case reports describing the anesthetic management of CCHS and ROHHAD patients . Data are further limited on the perioperative complications associated with thoracoscopic diaphragm pacemaker placement .…”

Section: Introductionmentioning

confidence: 99%

“…There are individual and compilations of case reports describing the anesthetic management of CCHS and ROHHAD patients. [13][14][15][16][17][18][19] Data are further limited on the perioperative complications associated with thoracoscopic diaphragm pacemaker placement. [8][9][10][11][12] Despite limited perioperative complications documented in the literature in patients with known CCHS and ROHHAD, 13 we hypothesized that these patients undergoing thoracoscopic phrenic nerve-diaphragmatic pacemaker insertion would be at high risk for cardiovascular instability and pulmonary issues under anesthesia due to their preoperative comorbidities, inability to mount adequate stress responses due to the innate autonomic dysregulation, and the need for sequential bilateral lung isolation.…”

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confidence: 99%

Perioperative anesthetic management of children with congenital central hypoventilation syndrome and rapid‐onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation undergoing thoracoscopic phrenic nerve‐diaphragm pacemaker implantation

Ballard

Leavitt

Chin

et al. 2018

Pediatric Anesthesia

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Summary Background Congenital Central Hypoventilation Syndrome and Rapid‐Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation are rare neurocristopathies characterized by autonomic dysregulation including bradyarrhythmias, abnormal temperature control, and most significantly, abnormal control of breathing leading to tracheostomy and ventilator dependence as life support. Surgical advancements have made phrenic nerve‐diaphragm pacemakers available, to eliminate the tether to a mechanical ventilator for 12‐15 hours each day. The thoracoscopic approach to implantation has allowed for a less invasive approach which may have implications for pain control and recovery time. However, thoracoscopic implantation of these devices presents several challenges to the anesthesiologist in these complex ventilator‐dependent patients, including, but not limited to, sequential lung isolation, prevention of hypothermia, and management of arrhythmias. Postoperative challenges may also include strategies to treat hemodynamic instability, managing the ventilator following lung derecruitment, and providing adequate pain control. Aims We aimed to describe the anesthetic management of Congenital Central Hypoventilation Syndrome and Rapid‐Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation patients undergoing thoracoscopic phrenic nerve‐diaphragm pacemaker implantation and the nature and incidence of perioperative complications. Methods A retrospective chart review was performed of 14 children with Congenital Central Hypoventilation Syndrome and Rapid‐Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation undergoing phrenic nerve‐diaphragm pacemaker implantation at a single academic pediatric hospital between 2009 and 2017. Demographic information, intraoperative management, and perioperative complications were analyzed from patient records. Results Twelve of 14 patients (86%) underwent an inhalational induction via tracheostomy. Lung isolation was achieved via fiberoptic guidance of a single lumen endotracheal tube sequentially into the right or left mainstem bronchi for 12 patients (86%). Double lumen endotracheal tubes were utilized in two patients (7%) and bronchial blockers in two patients (7%) for lung isolation. Anesthesia was maintained using a balanced technique of volatile agents (sevoflurane/isoflurane) and opioids (fentanyl). Bradyarrhythmias developed in six patients (43%) during surgery, 5 (36%) responded to anticholinergics and one patient (7%) required backup cardiac pacing using a previously implanted bipolar cardiac pacemaker. Intraoperative hypothermia (<35.5°C) was present in five patients (36%) despite the use of warming devices. Hypercarbia (>50 mm Hg) during lung isolation was present in eight patients (57%) and hemoglobin desaturation (<90%) in four patients (29%). Postoperatively, oxygen desaturation was a common complication with nine patients (64%) requiring supplemental oxygen administration via mechani...

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Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER Trafficking

Coghlan

Richards

Shaik

et al. 2018

Sci Rep

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Anesthetic agents have been implicated in the causation of neurological and cognitive deficits after surgery, the exacerbation of chronic neurodegenerative disease, and were recently reported to promote the onset of the neurologic respiratory disease Congenital Central Hypoventilation Syndrome (CCHS), related to misfolding of the transcription factor Phox2B. To study how anesthetic agents could affect neuronal function through alterations to protein folding, we created neuronal cell models emulating the graded disease severity of CCHS. We found that the gas anesthetic isoflurane and the opiate morphine potentiated aggregation and mislocalization of Phox2B variants, similar to that seen in CCHS, and observed transcript and protein level changes consistent with activation of the endoplasmic reticulum (ER) unfolded protein response. Attenuation of ER stress pathways did not result in a correction of Phox2B misfolding, indicating a primary effect of isoflurane on protein structure. We also observed that isoflurane hindered the folding and activity of proteins that rely heavily on ER function, like the CFTR channel. Our results show how anesthetic drugs can alter protein folding and induce ER stress, indicating a mechanism by which these agents may affect neuronal function after surgery.

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The paired-like homeobox 2B (PHOX2B) gene and respiratory control

Cited by 3 publications

References 21 publications

Trastornos De Hipoventilación Central Del Sueño en Pediatría: Causas Poco Frecuentes

Trastornos De Hipoventilación Central Del Sueño en Pediatría: Causas Poco Frecuentes

Perioperative anesthetic management of children with congenital central hypoventilation syndrome and rapid‐onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation undergoing thoracoscopic phrenic nerve‐diaphragm pacemaker implantation

Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER Trafficking

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