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.

The Respiratory and Autonomic Disorders of Infancy, Childhood and Adulthood-Foundation for Research and Education (RADICA-FRE), a new organization devoted to promoting research and educating families and healthcare workers about CCHS, is planned to launch in the spring of 2010.

Source: American Thoracic Society