Genetic segregation analysis of autonomic nervous system dysfunction in families of probands with idiopathic congenital central hypoventilation syndrome.

Idiopathic congenital central hypoventilation syndrome (CCHS) is a very rare syndrome with major respiratory complications. Hypothesizing that CCHS is the most severe manifestation of general autonomic nervous system dysfunction (ANSD), we applied a case-control family study design to investigate the genetics of ANSD. Fifty-two probands with CCHS were identified, as well as 52 age-, race-, and gender-matched controls. ANSD phenotypic features were characterized in the cases, controls, and their family members. Our earlier studies found that most ANSD symptoms were more likely in CCHS cases and their relatives than in controls and their relatives (P < 0.05). The goal of the current study was to determine if the familiality of ANSD was consistent with a genetic pattern. We performed major locus segregation analysis of ANSD utilizing regressive models. CCHS probands were assumed to be affected; controls and relatives were designated as affected if they had two or more relevant symptoms. The hypothesis of "no transmission and no familial effects" was rejected in both case and control families. Case families were consistent with transmission of a major effect; control families were not (the difference in the pattern of results was significant, P < 0.0001). In the total data set, the best-fitting model was codominant Mendelian inheritance of a major gene for ANSD. These case-control family studies support our hypothesis that CCHS is the most severe manifestation of a general ANSD, with a family pattern consistent with Mendelian transmission, and demonstrate the potential utility of the approach to studies of other, similarly intractable disorders.

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 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 > or =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.

SIDS risk factor awareness: assessment among nursing students.

OBJECTIVE: To test the hypotheses that nursing students (a) have limited knowledge of risk factors for sudden infant death syndrome (SIDS) and the American Academy of Pediatrics (AAP) recommendation of placing infants on their backs or sides for sleep, and (b) after careful education about SIDS, would retain this information and teach it to parents. DESIGN: A pretest questionnaire was used to identify knowledge of 13 risk factors and personal recommendation for sleep position. Participants attended a lecture on SIDS and received written educational material. A posttest was completed after 6 weeks. SETTING: Nursing students were assessed during their family practice course. PARTICIPANTS: Fifty-one 4th-year nursing students (mean age 28.4 years, SD=7.6) enrolled in the BSN program completed the pretest; 29 completed the identical posttest. INTERVENTION: A lecture on SIDS and SIDS risk factors with written educational material after the pretest. MAIN OUTCOME MEASURES: Pretest and posttest responses. RESULTS: The Mann-Whitney test and McNemar chi-square analyses were used to determine factors on the pretest which influenced the awareness of prone position and to compare pretest and posttest data. On the pretest, 69% of students were aware of the AAP recommendation but significantly more (92%) were aware on the posttest. Posttest responses increased significantly for 12 of the 13 risk factors; 41% of the students identified all 13 risk factors on the posttest, in contrast to 0% on the pretest. On both the pretest and posttest, 93% of students stated that it was important to discuss their infant's sleep position with parents. Posttest results showed that students unanimously recommend the side or back sleep position. CONCLUSION: Nursing students were aware of the AAP recommendation, yet their knowledge of other risk factors was limited. A careful educational process resulted in retention of information about the AAP recommendation and other risk factors. In addition, students were willing to teach parents to place their infants on the back or side to sleep.