Case/control family study of autonomic nervous system dysfunction in idiopathic congenital central hypoventilation syndrome

Debra E. Weese-Mayer*, Jean M. Silvestri, Angela D. Huffman, Sheilah M. Smok-Pearsall, Mary H. Kowal, Brion S. Maher, Margaret E. Cooper, Mary L. Marazita

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Children with idiopathic congenital central hypoventilation syndrome (CCHS) have a complex phenotype consistent with an imbalance of the autonomic nervous system (ANS). Since CCHS may be genetic in origin, we hypothesized that relatives of individuals with CCHS may exhibit symptoms of ANS dysfunction (ANSD), albeit in a milder form. We tested this hypothesis by assessing aspects of ANS function in relatives of CCHS cases vs. relatives of matched controls with a scripted questionnaire. Only those 35 symptoms of ANSD exhibited by ≥5% of the CCHS cases were included in the analysis as the basis for determining ANSD affection status. Two different arbitrary ANSD affection status definitions are presented in detail: any case, control, or relative with positive findings (1) in two or more symptoms, or (2) in two or more systems. The subjects included in the analysis totaled 2,353, including 56 CCHS cases, 56 age-, gender-, and race-matched controls, and their families. Under each of the two arbitrary ANSD affection statuses, CCHS cases and parents of cases were more likely to be affected than controls and parents of controls (P <0.001 for both comparisons), 16% of the CCHS siblings had the ANSD phenotype with two or more symptoms, compared to 4% of control siblings (P=0.03). Aunts and uncles of the CCHS cases were also significantly more likely to have two or more ANSD symptoms than were aunts and uncles of the controls (P=0.009). These results support our hypothesis and also indicate that relatives of the CCHS cases tended to manifest a milder spectrum of ANSD, with fewer systems and/or fewer symptoms than the cases.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalAmerican Journal of Medical Genetics
Issue number3
StatePublished - May 1 2001


  • Autonomic nervous system
  • Idiopathic congenital central hypoventilation syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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