Featured Research

from universities, journals, and other organizations

Disorder of respiratory and autonomic nervous system regulation

Date:
March 12, 2010
Source:
American Thoracic Society
Summary:
The American Thoracic Society has released a new official clinical policy statement on congenital central hypoventilation syndrome, a disorder of respiratory and autonomic nervous system (ANS) regulation. The ANS regulates reflexive acts, including heart rate and blood pressure, digestion, body temperature and pain perception.

The American Thoracic Society has released a new official clinical policy statement on congenital central hypoventilation syndrome (CCHS), a disorder of respiratory and autonomic nervous system (ANS) regulation. The ANS regulates reflexive acts, including heart rate and blood pressure, digestion, body temperature and pain perception.

The statement appears in the March 15, 2010 issue of the American Journal of Respiratory and Critical Care Medicine.

In light of a crucial discovery linking CCHS to mutations in a single gene, the new guidelines represent a complete overhaul of the guidelines the ATS last published in 1999. In 2003, a gene called PHOX2B was found to be the disease-defining gene for CCHS. The specific manner in which the PHOX2B gene mutates predicts the severity and form of the disease, making it a rich source of diagnostic and prognostic information.

"This discovery confirmed what we had long believed to be true: first, that CCHS is a genetic disorder; second, that the gene responsible for CCHS has a key role in the early embryology of the ANS; third, that inheritance of CCHS and the PHOX2B mutation is autosomal dominant; fourth, that the nature of the PHOX2B mutations can explain the spectrum of the CCHS phenotype; and so much more," explained Debra E. Weese-Mayer, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine, who chaired the committee that wrote the guidelines. "The discovery that PHOX2B is the gene that defines CCHS offers endless opportunities in terms of basic science inquiry and clinical care -- all with the long-term goal to improve quality of life for these patients."

By late 2009, collective publications from laboratories in the United States, France, Italy, Japan, Germany, Taiwan, China, the Netherlands and the United Kingdom have identified nearly 1,000 cases of PHOX2B mutation-confirmed CCHS.

The first sign of CCHS often appears just after birth, when affected infants will turn blue when they sleep, as their breathing becomes very shallow or even stops. Severely affected babies can also turn blue while awake. But now that CCHS is more widely recognized, patients are being identified in the newborn period with greater frequency. Those who were "missed" in early infancy and who have a milder presentation are now being identified in later childhood and even into adulthood. "They usually have a history of turning blue after receiving sedation, anesthesia or anti-seizure meds," explained Dr. Weese-Mayer. "They also may have exceptional talent at underwater swimming or breath-holding (due to an inability to perceive the sensation of asphyxia). Many later-presenting cases will have unexplained neurocognitive delay."

Afflicted individuals generally require fastidious medical supervision to attain the highest quality of life. The opportunity for PHOX2B clinical testing as soon as the diagnosis of CCHS is considered has expedited aggressive intervention and management. Early identification and intervention are critical to maintain optimal oxygenation and ventilation awake and asleep in these highly vulnerable, but extraordinarily "normal" children.

"When optimally managed, patients have attended college, married and held jobs," Dr. Weese-Mayer continued. "The aim is to identify the patients as early as possible, develop a teamwork approach to management so that family members, home nurses, pediatric pulmonologists, pediatricians and the CCHS Center that is treating the child all work together to maximize the quality of life and neurocognitive potential for patient -- and to minimize the risk for sudden death from respiratory insufficiency or cardiac pauses. Our aim is a lifetime of success for the individual with CCHS."

The new guidelines recommend a number of key management options for CCHS:

  • Biannual, then annual, comprehensive in-laboratory and in-patient evaluations that would last for several days, and which would include:
    • Physiological studies during wakefulness and sleep to assess ventilatory needs during different activities and sleep to ascertain safe conditions and ventilatory management recommendations;
    • Endogenous and exogenous gas challenges and autonomic testing to characterize the extent of compromise and to ascertain safe conditions;
    • 72-hour Holter monitoring of heart rhythm to identify asystoles, where the heart temporarily stops beating;
    • Echocardiograms to screen for effects of low oxygen; and
    • Comprehensive neurocognitive testing to measure success of the management and offer intervention options.
  • Barium enema or manometry and/or full thickness rectal biopsy for patients with a history of constipation to identify Hirschsprung disease; and
  • Imaging for neural crest tumors in individuals at risk based on their PHOX2B mutation.

Because PHOX2B exerts its influence so early in embryonic development, no gene therapy yet exists, though this will undoubtedly be a target of future investigations. Pre-implantation genetics will be another target. Prenatal testing for families with a known PHOX2B mutation is already available.

"Most PHOX2B mutations arise spontaneously, as long as neither parent is affected by CCHS. However, we demonstrated in 2003 that it is also possible for children to inherit the PHOX2B mutation from an unaffected parent. An estimated five to 10 percent of parents of children with CCHS will have mosaicism for the PHOX2B mutation, meaning that they will have the same mutation as their child, but in only a subset of their cells. These parents can pass the mutation on to their offspring with up to a 50-percent risk of transmission in each pregnancy," said Dr. Weese-Mayer.

Currently, the population incidence of PHOX2B mutations across all ethnicities is unknown, but future research will be focused on using the current base of knowledge about CCHS to answer such questions. Dr. Weese-Mayer points to the section of the new ATS statement that deals with "future directions" -- outlining the need for prospective studies on large cohorts of children and adults with CCHS to more clearly define the clinical features by specific PHOX2B mutation; the development of animal models to study the mutations and understand their pathology and clinical manifestations; stem cell research to better understand how each organ system can be affected by PHOX2B mutations; and collaboration between clinical physicians, physician-scientists and basic science researchers to better understand and treat the disease.


Story Source:

The above story is based on materials provided by American Thoracic Society. Note: Materials may be edited for content and length.


Cite This Page:

American Thoracic Society. "Disorder of respiratory and autonomic nervous system regulation." ScienceDaily. ScienceDaily, 12 March 2010. <www.sciencedaily.com/releases/2010/03/100312134939.htm>.
American Thoracic Society. (2010, March 12). Disorder of respiratory and autonomic nervous system regulation. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2010/03/100312134939.htm
American Thoracic Society. "Disorder of respiratory and autonomic nervous system regulation." ScienceDaily. www.sciencedaily.com/releases/2010/03/100312134939.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins