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)

Congenital central hypoventilation syndrome (CCHS) is a rare disorder where there is failure of automatic control of breathing. With improved recognition of CCHS, more children are appropriately diagnosed and treated in infancy, allowing survival into adult years. Because most of these children are able to participate in regular school, they are exposed to common adolescent behaviors, such as abusing alcohol and drugs. Alcohol and many illicit substances are known respiratory depressants. We report on 3 cases of adolescents/young adults with CCHS who had severe adverse events related to alcohol, including coma and death. This series illustrates the dangers of alcohol abuse in CCHS. We speculate that adolescents with CCHS may be less able to perceive the risks of substance abuse and impulsive behavior, leading to increased morbidity and mortality. Patients with CCHS appear to lack anxiety and the awareness that their inability to perceive physiologically dangerous levels of hypercarbia and hypoxia deprives them of important protective mechanisms.
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PMID:Alcohol use in congenital central hypoventilation syndrome. 1642 33

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy characterized by absence of automatic control of respiration; decreased sensibility to hypoxia and hypercapnia, mainly during sleep; and autosomal dominant inheritance due to heterozygous polyalanine expansions and frameshift mutations in the PHOX2B gene. Because the CCHS phenotype could hide other neurologic diseases, the American Thoracic Society established that the initial evaluation of suspected CCHS should exclude neuroanatomic impairments as the structural basis of the reduced autonomic system function. In this work, we describe the clinical history of two unrelated patients with hypoventilation during sleep and harboring hypoplasia of the pons and a Chiari I malformation, respectively. In both patients, CCHS was diagnosed by detection of PHOX2B polyalanine expansion, suggesting that the American Thoracic Society diagnostic criteria may be too restrictive. Moreover, to exclude a putative role of PHOX2B in non-CCHS neurologic diseases, we have performed PHOX2B mutation screening in a group of individuals with Chiari I malformation, confirming the exclusive role of PHOX2B in the pathogenesis of CCHS.
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PMID:Brainstem anomalies in two patients affected by congenital central hypoventilation syndrome. 1676 19

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V'(R,CO(2))) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V'(R,CO(2)), despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67-83%) and V'(R,CO(2)) was 2.1 (0.03-4.3) L x min(-1) x kPa(-1). The normal values for the authors' centre (St Vincent's University Hospital, Dublin, Ireland) are 15-40 L x min(-1) x kPa(-1). An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.
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PMID:Late-onset central hypoventilation syndrome: a family genetic study. 1726 23

Hirschsprung's disease (HSCR) is characterized by the absence of intramural ganglion cells in the distal gut, resulting in bowel obstruction shortly after birth. Congenital central hypoventilation syndrome (CCHS) results in hypoventilation, most pronounced during sleep, with relative insensitivity to hypercarbia and reduced insensitivity to hypoxia. Congenital central hypoventilation syndrome with HSCR is a rare condition with variable severity. Both CCHS and HSCR are uncommon and their co-occurrence may suggest a common etiology, probably involving a fault of neural crest development. Recent reports have identified the paired-like homeobox 2B (PHOX2B) gene as the major gene for CCHS and HSCR. We report here an identified PHOX2B gene in a newborn baby who had concurrence of CCHS and total colonic aganglionosis with proximal small bowel involvement. Management of this rare disorder is challenging not only because it presents in newborn stage but also because it has extensive HSCR. Considering the issue of medical futility, the therapeutic and ethical dilemma of this infant was discussed.
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PMID:Concomitant existence of total bowel aganglionosis and congenital central hypoventilation syndrome in a neonate with PHOX2B gene mutation. 1727 May 34

Congenital central hypoventilation syndrome (CCHS) is a rare disease that is characterized by failure in the autonomic control of breathing. Recent reports have identified mutation of the paired mesoderm homeobox protein 2b (PHOX2B) gene as playing a major role in CCHS. Increasing polyalanine repeat number is associated with a more severe clinical phenotype. We report a newborn male infant with the clinical manifestations of apnea and cyanosis requiring immediate endotracheal intubation at the age of 1 day. Recurrent hypoventilation with hypercapnia and hypoxemia occurred during sleep after weaning from the ventilator. No primary cardiopulmonary disease was identified. These clinical manifestations are compatible with CCHS. PHOX2B gene mutation analysis performed at the age of 4 months revealed expanded alleles containing polyalanine 26 repeats, further supporting the diagnosis of CCHS. Continuous ventilator support was necessary and tracheostomy was ultimately performed at the age of 5 months due to ventilator dependence. He was discharged with home ventilator support at the age of 6 months.
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PMID:Congenital central hypoventilation syndrome with PHOX2B gene mutation in a Taiwanese infant. 1728 73

Congenital central hypoventilation syndrome (CCHS) is a rare disease with variable severity, generally present from birth and chiefly characterized by impaired chemosensitivity to hypercapnia. The main cause of CCHS is a mutation in the PHOX2B gene, which encodes a transcription factor involved in the development of autonomic medullary reflex pathways. Temperature regulation is abnormal in many patients with CCHS. Here, we examined whether ambient temperature influenced CO(2) sensitivity in a mouse model of CCHS. A weak response to CO(2) at thermoneutrality (32 degrees C) was noted previously in 2-day-old mice with an invalidated Phox2b allele (Phox2b+/-), compared with wild-type littermates. We exposed Phox2b+/- pups to 8% CO(2) at three ambient temperatures (TAs): 29 degrees C, 32 degrees C, and 35 degrees C. We measured breathing variables and heart rate (HR) noninvasively using a novel whole body flow plethysmograph equipped with contact electrodes. Body temperature and baseline breathing increased similarly with TA in mutant and wild-type pups. The hypercapnic ventilatory response increased linearly with TA in both groups, while remaining smaller in mutant than in wild-type pups at all TAs. The differences between the absolute increases in ventilation in mutant and wild-type pups become more pronounced as temperature increased above 29 degrees C. The ventilatory abnormalities in mutant pups were not associated with significant impairments of heart rate control. In both mutant and wild-type pups, baseline HR increased with TA. In conclusion, TA strongly influenced the hypercapnic ventilatory response in Phox2b+/- mutant mice. These findings suggest that abnormal temperature regulation may contribute to the severity of respiratory impairments in CCHS patients.
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PMID:Effects of temperature on ventilatory response to hypercapnia in newborn mice heterozygous for transcription factor Phox2b. 1771 84

Congenital central hypoventilation syndrome most commonly presents in neonates with sleep related hypoventilation; late onset cases have occurred up to the age of 10 years. It is associated with mutations in the PHOX2B gene, encoding a transcription factor involved in autonomic nervous system development. The case history is described of an adult who presented with chronic respiratory failure due to PHOX2B mutation-associated central hypoventilation and an impaired response to hypercapnia.
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PMID:Central hypoventilation with PHOX2B expansion mutation presenting in adulthood. 1790 90

Congenital Central Hypoventilation Syndrome is a rare disorder of autonomic dysfunction where the body "forgets to breathe". The primitive responses to hypoxia and hypercapnia are sluggish to absent. Since, it was first described in 1970, not much has been discovered about its etiology and pathophysiology except its relationship with PHOX2B gene mutations and associations with disorders of neural crest origin like Hirschprung's Disease. Here, we describe such a case where the diagnosis of anything other than CCHS seems unlikely.
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PMID:Congenital central hypoventilation syndrome. 1797 58

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) is a rare disorder with uncertain nosology that usually presents early in life. The syndrome is characterized by ventilatory response impairment to carbon dioxide and may result in respiratory failure at birth. Recent reports have identified a similar clinical presentation beyond infancy called late-onset central hypoventilation syndrome (LO-CHS) as a disease continuum of CCHS with similar and overlapping pathophysiology. However, some have proposed that the syndrome accompanied by hypothalamic dysfunction (HD) be classified as a distinct clinical entity, LO-CHS/HD. To the best of our knowledge, the case reported herein is the oldest case of LO-CHS/HD in childhood, at 13 years old. He suffered from recurrent pulmonary edema, acute convulsive seizures, hypersomnia, hyperphagia, obesity, impaired glucose tolerance test, and hypercapnia, diagnosed as LO-CHS/HD, and was successfully treated with nasal bi-level positive airway pressure.
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PMID:A case of late-onset central hypoventilation syndrome with hypothalamic dysfunction: through a new phenotype. 2056 Feb 60


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