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

Children with idiopathic congenital central hypoventilation syndrome (CCHS) have a complex phenotype consistent with an imbalance of the autonomic ner vous system (ANS). Since CCHS may be genetic in origin, we hypothesized tha t relatives of individuals with CCHS may exhibit symptoms of ANS dysfunctio n (ANSD), albeit in a milder form. We tested this hypothesis by assessing a spects of ANS function in relatives of CCHS cases vs. relatives of matched controls with a scripted questionnaire. Only those 35 symptoms of ANSD exhi bited by greater than or equal to5% 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 ca se, 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 tota led 2.353, including 56 CCHS cases, 56 age-, gender-, and race-matched cont rols, and their families, Under each of the two arbitrary ANSD affection st atuses, CCHS cases and parents of cases were more likely to be affected tha n 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, compar ed 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 o ur hypothesis and also indicate that relatives of the CCHS cases tended to manifest a milder spectrum of ANSD, with fewer systems and/or fewer symptom s than the cases. <(c)> 2001 Wiley-Liss, Inc.