CF carrier testing in a high risk population: anxiety, risk perceptions, and reproductive plans of carrier by "non-carrier" couples.

PURPOSE: The risk perceptions, psychological status and reproductive plans of 52 carrier by "noncarrier" (mutation screen negative) couples is the subject of this report. METHODS: Cystic fibrosis (CF) carrier testing was offered to relatives of individuals with CF. RESULTS: In this population testing was not associated with any significant adverse psychological effects, reproductive uncertainty, or inaccurate risk perceptions. CONCLUSIONS: The results of this study have important implications in light of the recent NIH CF Consensus Panel recommendations that CF carrier testing be offered to all high risk adults and all couples planning a pregnancy or seeking prenatal testing.

Psychosocial and educational outcomes associated with home- and clinic-based pretest education and cystic fibrosis carrier testing among a population of at-risk relatives.

We report on the psychosocial and knowledge outcomes of two different approaches to cystic fibrosis (CF) gene pretest education and carrier testing offered to 288 proactively recruited first-, second-, and third-degree relatives of people with CF. One group received pretest education and gene testing in a clinical setting from a certified genetic counselor. The other group received pretest education in their homes from a specially prepared pamphlet and were asked to send in a buccal cell sample for genotyping. No statistically significant differences between groups were noted on measures of CF knowledge, anxiety, and positive or negative affect, either while waiting for their test results or within a few weeks after they had learned their results. At both measurement points, participants who had received home education and testing reported that the testing was more convenient, but that they had received less information than they would have liked, and they were more likely to report being confused by the testing, although their level of CF knowledge was comparable to that of people who had been seen by a genetic counselor. In light of the increasing interest in home-based medical testing of all kinds, this study suggests that CF carrier testing in the home warrants further consideration as one possible approach to facilitating access to testing.

Prenatal exposure to disulfiram implicated in the cause of malformations in discordant monozygotic twins.

Female monozygotic (MZ) twins were discordant for congenital structural anomalies: Twin A had a reduction defect of the right forearm; Twin B had a cleft palate. Both infants were small for gestational age. Specific prenatal exposures were identified at different times in the first trimester of pregnancy: crack cocaine, marijuana, disulfiram, heavy ethanol exposure, and cigarettes. The mother's hospitalization in a drug abuse program and incarceration allowed for identification of exposure timing. The cleft palate could have been related to either disulfiram or alcohol exposure; the limb abnormality most likely corresponded to the timing of disulfiram exposure. Discordance of anomalies in these twins may reflect differences in developmental timing, differences in susceptibility to one or more teratogens, or random events occurring within very complex developmental programs, with the thresholds for malformation affected by one or multiple teratogenic compounds.

CF carrier testing: Experience of relatives.

Consensus exists that genetic counseling and CF carrier testing should be offered to individuals with a positive family history of CF. To learn more about their experience with genetic counseling and testing we conducted a series of structured telephone interviews and focus group discussions with individuals and couples who had undergone genetic counseling and carrier testing because of a family history of CF. Traditional genetic counseling appears to have been effective for this population. Subjects generally report having a positive counseling experience and few difficulties upon learning their carrier status. Subjects were quite knowledgeable about CF and their carrier risk and were highly motivated to seek testing. They may not be representative of all individuals with a family history of CF however. For carriers, concerns about whether and when to have children tested, and concerns about insurance implications of carrier status may emerge sometime after the initial counseling. Strategies for addressing these concerns and for providing efficient and effective education and genetic counseling for people with a family history of CF need to be developed.

Molecular characterisation of chromosome 4p deletions resulting in Wolf-Hirschhorn syndrome.

We present three patients with Wolf-Hirschhorn syndrome with small cytogenetic deletions of 4p16. One case is a de novo translocation and two cases represent de novo deletions. Using molecular techniques we determined the extent of these deletions and attempted to ascertain parental origin. Case 1 had a deletion of 4p16.3 with a breakpoint proximal to D4S10, case 2 had a larger deletion including D4S62 in 4p16.2, and case 3 had the largest deletion which included D4S240, but not the Raf2 locus in 4p16.1. The parental origin of the deletion in case 3 was paternal; the other two cases were indeterminable. Our results show that these three deletions include the currently proposed Wolf-Hirschhorn syndrome critical region within the most distal 2 Mb of 4p16.3 and offer supportive evidence for continuous terminal deletions.

A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.

We report two families with a satellited chromosome 4 short arm (4ps). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited nonacrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is the first report of 4ps chromosomes. Our families are remarkable in that both unaffected and affected individuals carry the 4ps chromosome. The phenotypes observed in affected individuals, although dissimilar, were sufficient to encourage a search for a deletion of chromosome 4p. By Southern blot analysis and fluorescence in situ hybridization, a deletion of material mapping approximately 150 kb from chromosome 4pter was discovered. This deletion is notable because it does not result in the Wolf-Hirschhorn syndrome and can result in an apparently normal phenotype. We speculate that homology between subterminal repeat sequences on 4p and sequences on the acrocentric short arms may explain the origin of the rearrangement and that position effect may play a role in the expression of the abnormal phenotype.

A supportive intervention protocol for couples terminating a pregnancy for genetic reasons.

This protocol recognizes the couple's sense of loss, the reality of their situation, and their decision to terminate the pregnancy. Couples who participated in our protocol reported that their involvement had a favorable effect on their experience and adjustment. In addition, the loss of the pregnancy does not seem to discourage them from pursuing future pregnancies or utilizing prenatal diagnostic services. This support protocol may be used as a model to be incorporated into prenatal diagnosis clinics and genetic counseling programs.