Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic congenital central alveolar hypoventilation syndrome, otherwise known as Ondine's curse, is a rare neuropathologic syndrome characterized by an inadequate respiratory drive with hypoventilation and periods of prolonged apnea resulting in hypercarbia and hypoxemia. Although no definite pathologic abnormality has been identified to account for the disorder, it is thought to represent a primary defect related to altered function of central chemoreceptors resulting in defective control of minute ventilation. Associated problems related to neural crest cell migration, including neuroblastoma formation and Hirschsprung's disease, suggest that the primary defect is defective neural crest cell migration and function. Problems that may impact on perioperative care include the defective central control of ventilation and defective control of upper respiratory musculature, which may lead to upper airway obstruction. Although many patients will have previously undergone tracheostomy and chronic mechanical ventilation, problems in other organ systems can impact on perioperative care. Cardiovascular issues include the possible presence of cor pulmonale and autonomic nervous system dysfunction. Central nervous system issues include the frequent occurrence of seizures and mental retardation. The preoperative work-up, premedication, and the intraoperative/postoperative care and monitoring of these patients is reviewed.
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PMID:Anesthetic care for the child with congenital central alveolar hypoventilation syndrome (Ondine's curse). 1052 17

Ischemic lesions of the brainstem can lead to complex neurologic deficits. Failure of the automatic control of ventilation (Ondine's curse syndrome) is a possible but rare syndrome following localized brainstem dysfunction. We report on a 49-year-old man with intermittent bradycardia, cranial nerves' dysfunctions and a slight right-sided hemiparesis. An acute brainstem ischemia was diagnosed and treated immediately with high-dose heparin. Cerebral angiography revealed a proximal occlusion of the left vertebral artery but a normal right vertebral artery and a hyperplastic right posterior inferior cerebellar artery. Cranial Computed Tomography and MRI scan demonstrated multiple ischemic lesions in the posterior circulation. During a 4-week treatment course the patient underwent six episodes of acute severe hypoxia and hypercapnia requiring orotracheal intubation twice and manual ventilation by air mask over a few minutes for four times after a tracheostomy had been performed. Twice a short-term episode of hypothalamic Diabetes insipidus was observed following hypoventilation. We conclude that both Ondine's curse syndrome and diabetes insipidus were due to transient vertebrobasilar ischemia.
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PMID:Ondine's curse in association with diabetes insipidus following transient vertebrobasilar ischemia. 1053 7

We report a female newborn with Ondine's curse and Hirschsprung's disease--neurocristopathic syndrome. The female infant required endotracheal intubation and mechanical ventilation due to apnea which developed soon after birth. She had abdominal distension with bilious vomiting. A barium enema revealed a caliber change at the rectum and rectal biopsies showed no ganglion cells. Colostomy was performed at the age of 17 days. Hypoxemia with hypercapnia was noted during her sleep, and tracheostomy was performed at the age of 55 days. In addition, deafness and pupillary autonomic dysfunction were observed. The definitive surgery for Hirschsprung's disease was performed at the age of 4 months. She is now 2 years old with normal growth but needs ventilator support at home. In this case, we detected no mutation in the RET gene and EDNRB gene.
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PMID:Ondine's curse and Hirschsprung's disease: neurocristopathic syndrome. 1066 60

Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a life-threatening disorder involving an impaired ventilatory response to hypercarbia and hypoxemia. This core phenotype is associated with lower-penetrance anomalies of the autonomic nervous system (ANS) including Hirschsprung disease and tumors of neural-crest derivatives such as ganglioneuromas and neuroblastomas. In mice, the development of ANS reflex circuits is dependent on the paired-like homeobox gene Phox2b. Thus, we regarded its human ortholog, PHOX2B, as a candidate gene in CCHS. We found heterozygous de novo mutations in PHOX2B in 18 of 29 individuals with CCHS. Most mutations consisted of 5-9 alanine expansions within a 20-residue polyalanine tract probably resulting from non-homologous recombination. We show that PHOX2B is expressed in both the central and the peripheral ANS during human embryonic development. Our data support an essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the ANS in humans.
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PMID:Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. 1266 62

An increase in arousal in response to hypercapnia [elevated arterial PCO2 (partial pressure of CO2) levels] during awake or sleep states is an important component of mechanisms designed to maintain acid-base homeostasis. Since central histaminergic neurons are crucial for maintaining waking states and vigilance, a nonresponsive or dysfunctional histaminergic system could contribute to the lack of arousal in response to hypercapnia in some sleep-related disorders [e.g., sudden infant death syndrome (SIDS) and Ondine's curse]. Therefore, the present study attempted to determine if histaminergic neurons display functional responses to acute exposure to hypercapnic gas (i.e., gas with elevated CO2 concentrations). Healthy adult male rats were placed in flow cages during the light cycle, or inactive phase, and exposed to either atmospheric air or to environmental CO2 concentrations increasing from baseline up to 20% CO2 over a 5-min period. The expression of the protein product of the immediate-early gene c-fos was used as a measure of functional cellular responses within subpopulations of histaminergic neurons. Among the histaminergic subgroups (E1-E5), only the ventral tuberommamillary nucleus (VTMn)/E2 cell group showed significant increases in c-Fos expression following brief exposure to hypercapnic gas. These data are consistent with the hypothesis that histaminergic neuronal cell groups are heterogeneous and are involved in physiological and/or behavioral responses to acute hypercapnic challenge, potentially increasing vigilance during active waking and awakening from sleep during hypercapnic states.
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PMID:Are tuberomammillary histaminergic neurons involved in CO2-mediated arousal? 1581 81

Congenital central hypoventilation syndrome (CCHS), or Ondine's curse syndrome, is a rare genetic disorder associated with mutations of the PHOX2B gene. It is characterized by sleep-related life-threatening hypoventilation that requires mechanical ventilation. The ventilatory response to hypercapnia and hypoxia is absent or dramatically reduced. Spontaneous or pharmacologically induced recovery has never been reported. We have fortuitously observed a case of CO(2)-chemosensitivity recovery in a woman with CCHS who took a progestin contraceptive - desogestrel. We hypothesized that the desogestrel could be responsible for this effect. We tested this hypothesis in a second adult patient. Her lack of CO(2)-chemosensitivity was documented 5 months before she was prescribed desogestrel. Three weeks after initiation of the treatment she exhibited a ventilatory and sensory response to hypercapnia. This response persisted 3 weeks later. This is the first documented case of pharmacologically restored chemosensitivity in CCHS. It suggests that a very potent progestin such as desogestrel could unveil latent chemosensitive neural circuits.
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PMID:Chemosensitivity recovery in Ondine's curse syndrome under treatment with desogestrel. 2030 19

Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse, is characterized by idiopathic failure of autonomic breathing and is often associated with neurocristopathies such as Hirschsprung disease (HSCR). CCHS is caused by mutations in the paired-like homeobox 2B (PHOX2B) gene, often manifest as polyalanine repeat expansions. Herein, we report the cases of two unrelated Korean patients with Ondine-Hirschsprung disease. The patient's clinical manifestations were apnea and cyanosis requiring immediate endotracheal intubation, recurrent hypoventilation with hypercapnia, hypoxia after ventilator removal, and abdominal distension since birth. Intestinal biopsies were performed and the absence of ganglion cells in the colon was consistent with HSCR. We performed direct sequencing analysis in the PHOX2B and RET genes and fluorescence polymerase chain reaction in order to determine the polyalanine tract expansion in exon 3 of the PHOX2B gene. Expansion mutations were detected in both patients; one had 20/24 repeats and the other had 20/27 repeats. The 20/24 genotype has not been previously described in severe CCHS phenotypes and associated HSCR. We believe that the information in this report will improve our understanding of the phenotypic and genotypic heterogeneities of CCHS and HSCR.
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PMID:PHOX2B mutations in patients with Ondine-Hirschsprung disease and a review of the literature. 2137 76

Ondine's curse syndrome primarily refers to cases with congenital central alveolar hypoventilation, but the term can also be used for acquired cases and implies central sleep apnea that occurs as a manifestation or complication of focal lesion in the area of the dorsolateral segment of medulla oblongata. It occurs rarely, but can lead to fatal outcome. Based on our own case report, the aim of this article is to review its clinical symptoms, and appropriate diagnostic and therapeutic procedures. We present a patient who had symptoms of vascular lesion of the dorsolateral segment of the medulla, which was verified by magnetic resonance imaging. On day 12 of his hospital stay, in the early morning, rapid development of coma was observed, which was an expression of serious respiratory failure with dominant hypercapnia. In the beginning, urgent intubation and mechanical ventilation were necessary, while in the later course of the disease breathing was assisted by noninvasive methods of Bilevel Positive Airway Pressure (BiPAP) and Continuous Positive Airway Pressure (CPAP). Throughout the night, polygraph recording confirmed the diagnosis of the central sleep apnea syndrome. The course of the disease was favorable, with a very slow but constant improvement of respiratory function. According to literature data, the disease course is not always favorable. There are published cases where it was concluded that ventilatory support was no longer needed but after a long period of normal breathing hypoventilation and death occurred suddenly during sleep. The treatment of central hypoventilation consists of ventilatory support, but there were also attempts of medicamentous treatment with the common aim of raising alertness and reactibility of the automatic breathing center. It is important to emphasize that patients with the risk of central sleep apnea should not be supplied with oxygen without arterial blood gas monitoring because of the possibility of delaying the right diagnosis. The use of oxygen in patients who already have hypercapnia due to hypoventilation could further intensify hyporeactivity of the breathing center and lead to respiratory arrest.
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PMID:[Central sleep apnea (Ondine's curse syndrome) in medullary infarction]. 2168 13

Ondine's curse is an eponym that refers to central alveolar apnea/hypopnea observed among patients with acquired or congenital brainstem disorders. This condition results in loss of automatic and/or voluntary respiration with characteristic polysomnographic finding of impaired ventilator responses to hypercapnia and sleep apnea, which are more pronounced during non-REM sleep, less in REM sleep, and least during wakefulness.
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PMID:Pearls and oy-sters: reversible Ondine's curse in a case of lateral medullary infarction. 2329 34

The association of congenital central hypoventilation syndrome (also known as Ondine's curse) and Hirschsprung's disease is termed Haddad syndrome, which is an extremely rare disorder. Recent studies have described that the PHOX2B gene mutation was responsible for congenital central hypoventilation syndrome. We report a term newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnia and bowel obstructions. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprung's disease. PHOXB direct sequencing showed a heterozygous in-frame duplication of 21 bp leading to an expansion of +7 alanines within the 20 alanine stretch of the PHOX2B gene and confirmed our diagnosis. In addition to a high index of clinical suspicion, testing for PHOX2B mutation can assist iq the diagnosis of congenital central hypoventilation syndrome and in the prediction of disease progression. Infants presenting with congenital central hypoventilation syndrome should also be screened for Hirschsprung's disease.
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PMID:Congenital central hypoventilation syndrome with hirschsprung's disease due to PHOX2B gene mutation in a Turkish infant. 2342 17


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