Idiopathic congenital central hypoventilation syndrome: the next generation

Abstract

Idiopathic congenital central hypoventilation syndrome (CCHS) is a rare disorder in which affected children have a decreased sensitivity of their respiratory centers to hypercarbia and hypoxia, as well as evidence for generalized autonomic nervous system dysfunction. A genetic origin has long been hypothesized for CCHS. Previous reports of the syndrome among twins, siblings, and half siblings, as well as an established association with Hirschsprung disease and neural crest tumors support this genetic hypothesis. Here, we present the first reported offspring born to four women diagnosed with idiopathic CCHS. Their children display a spectrum of abnormalities with one child being diagnosed with CCHS, one child with recurrent apparent life threatening events, one infant born prematurely with severe chronic lung disease and diminished ventilatory responses to carbon dioxide, and one infant who is apparently healthy with no clinical manifestations suggestive of disordered respiratory control to date. Two and potentially three of these patients illustrate transmission of altered respiratory control by CCHS patients into the next generation, furthering the evidence that CCHS is part of a broadly based inherited syndrome of autonomic nervous system dysfunction.

Case report of Haddad syndrome in a newborn: congenital central hypoventilation syndrome and Hirschsprung's disease

“…Prenatal testing for pregnancies at risk is possible if the expansion mutation has been identified in an affected family member. 6,9 Hypoventilation in CCHS is the result of depressed or absent ventilatory sensitivity and arousal response to hypercarbia and hypoxemia or combination of both. Perception of asphyxia is absent; so affected children do not develop dyspnea in response to increased oxygen demand while exercising or in case of respiratory infection.…”

“…Other autonomic nervous system dysfunctions, tumors of neural crest origin (such as neuroblastoma, ganglioneuroma and ganglioneuroblastoma) and Hirschsprung's disease are often found in affected children. [3][4][5][6] CCHS associated with Hirschsprung's disease is known as the Haddad syndrome. It is named after the author who first described three newborns with absent control of breathing and Hirschsprung's disease.…”

Genetics and Early Disturbances of Breathing Control: The Genetics of Childhood Disease and Development: A Series of Review Articles

“…More importantly, vertical transmission of CCHS has been reported: among babies born to five women with CCHS but no HSCR (19,20), two had CCHS, suggesting autosomal dominant inheritance (19,20). A third infant exhibited recurrent episodes of ALTE consistent with a link between CCHS and ALTE (20). The fourth infant was born prematurely and had severe bronchopulmonary dysplasia.…”

“…The fourth infant was born prematurely and had severe bronchopulmonary dysplasia. Finally, one child was apparently healthy (20). In addition, a child with CCHS was born to a mother who had a neural crest tumor, suggesting differences in the clinical expression of neural crest disorders (21).…”

“…It is also essential to disseminate information on the potential transmission of CCHS to CCHS families, obstetricians, and pediatricians. Moreover, meticulous attention should be paid to infants whose mothers or fathers have CCHS (20). An international database including clinical data and genetic specimens from CCHS patients and their parents and relatives is needed.…”