CONGENITAL CENTRAL HYPOVENTILATION SYNDROME - INHERITANCE AND RELATION TO SUDDEN-INFANT-DEATH-SYNDROME

We evaluated the families of 50 children with idiopathic congenital ce ntral hypoventilation syndrome (CCHS) to 1) test genetic hypotheses, 2 ) explore the relationship to Hirschsprung disease (HD), and 3) examin e other clinical findings including sudden infant death syndrome (SIDS ) in relatives of CCHS patients. A questionnaire was administered to p arents of each proband to determine a detailed pedigree and medical hi story for 3 generations including 1,482 relatives. The data were analy zed under the unified mixed model method (assumes individual genotype composed of multifactorial [MF] and major locus [ML] components). Anal ysis was made of the Total dataset and on subdivided data sets: HIRI = families of probands with HD (n = 8) vs. HIR2 = families of probands without HD; then under a premise that severe, chronic constipation may be a milder form of HD (i.e., ganglion cells present but dysfunctiona l), CON1 = families of probands with HD or constipation (n = 13) vs. C ON2 = families of probands without HD or constipation. By statistical genetic analysis of the Total, HIR1, and CON1 datasets, the MF and ML hypotheses were about equally likely, with the MF model slightly more parsimonious. Although HIR2 and CON2 datasets indicated no familiality , statistical evidence of heterogeneity between the results of HIR1 an d HIR2, or between CON1 and CON2 was lacking. A SIDS incidence of 11.2 /1,000 was documented among the relatives of CON1 vs. 1.8/1,000 among relatives of CON2. Our results are consistent with familiality by eith er MF or ML models. Recurrence risk is likely <5%. The relationship of CCHS to the high familial incidence of SIDS is intriguing and demands further investigation. (C) 1993 Wiley-Liss, Inc.