Congenital Central Hypoventilation Syndrome
It is possible that the main title of the report Congenital Central Hypoventilation Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
- autonomic control, congenital failure of
- Ondine curse, congenital
- CCHS with Hirschsprung disease, included
Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory control and autonomic nervous system (ANS) regulation. Respiratory control is the automatic function of breathing in response to varied activities of daily living (ex. exercise, concentration, sleep, eating), so within the context of the ANS. The ANS is the portion of the nervous system that controls or regulates many involuntary body functions including heart rate, blood pressure, temperature regulation, bowel and bladder control, breathing, and more. Impaired breathing regulation (respiratory control) is the hallmark of CCHS. Individuals with CCHS typically present in the newborn period with inadequate shallow breathing (alveolar hypoventilation) during sleep and, in more severely affected individuals, during wakefulness and sleep. Breathing complications occur despite normal lungs and a normal airway, because of the abnormal control of breathing. A growing number of individuals are now being identified whose symptoms were not apparent until later infancy, childhood, or even adulthood and are called later onset congenital central hypoventilation syndrome (LO-CCHS).
All individuals with CCHS have a mutation in the PHOX2B gene. The PHOX2B gene plays an important role in the prenatal development of the ANS. The normal PHOX2B gene has a region with 20 repeats of a code for the amino acid, alanine. For those individuals with CCHS, the majority (~90%) have a mutation causing an increase in the number of these alanine repeats above the normal 20 alanines. This is called a polyalanine repeat expansion mutation (PARM). The expansion can be from 24 to 33 alanines, so the genotype for CCHS patients will be 20/24-20/33 (reflecting the normal number of alanines on the normal gene (n=20) and the number of alanines on the abnormal gene (n==24-33). The remaining individuals with CCHS have a different type of abnormality in the PHOX2B gene. These other mutations in the PHOX2B gene are called non-polyalanine repeat expansion mutations (NPARM). They can be missense, nonsense, frameshift, or stop codon mutations and they will typically severely alter the protein coded by the PHOX2B gene.
CCHS Family Network (Congenital Central Hypoventilation Syndrome)
71 Maple Street
Oneonta, NY 13820
NIH/National Institute of Neurological Disorders and Stroke
P.O. Box 5801
Bethesda, MD 20824
International Foundation for Functional Gastrointestinal Disorders
700 W. Virginia St., 201
Milwaukee, WI 53217
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126