Do parental perceptions and motivations towards genetic testing and prenatal diagnosis for deafness vary in different cultures?

Surveys of attitudes of individuals with deafness and their families towards genetic testing or prenatal diagnosis have mostly been carried out in the West. It is expected that the perceptions and attitudes would vary amongst persons of different cultures and economic background. There is little information on the prevailing attitudes for genetic testing and prenatal diagnosis for deafness in developing countries. Therefore, this study evaluates the motivations of Indian people with inherited hearing loss towards such testing. Twenty‐eight families with history of congenital hearing loss (23 hearing parents with child/family member with deafness, 4 couples with both partners having deafness and 1 parent and child with deafness) participated in a semi‐structured survey investigating their interest, attitudes, and intentions for using genetic and prenatal testing for deafness. Participants opinioned that proper management and care of individuals with deafness were handicapped by limited rehabilitation facilities with significant financial and social burden. Nineteen (68%) opted for genetic testing. Twenty‐six (93%) expressed high interest in prenatal diagnosis, while 19 (73%) would consider termination of an affected fetus. Three hearing couples, in whom the causative mutations were identified, opted for prenatal diagnosis. On testing, all the three fetuses were affected and the hearing parents elected to terminate the pregnancies. This study provides an insight into the contrasting perceptions towards hearing disability in India and its influence on the desirability of genetic testing and prenatal diagnosis. © 2012 Wiley Periodicals, Inc.     

The role of anticipated regret and health beliefs in HPV vaccination intentions among young adults

Although cognitions have predicted young adults’ human papillomavirus (HPV) vaccine decision-making, emotion-based theories of healthcare decision-making suggest that anticipatory emotions may be more predictive. This study examined whether anticipated regret was associated with young adults’ intentions to receive the HPV vaccine above and beyond the effects of commonly studied cognitions. Unvaccinated undergraduates (N = 233) completed a survey assessing Health Belief Model (HBM) variables (i.e., perceived severity of HPV-related diseases, perceived risk of developing these diseases, and perceived benefits of HPV vaccination), anticipatory emotions (i.e., anticipated regret if one were unvaccinated and later developed genital warts or HPV-related cancer), and HPV vaccine intentions. Anticipated regret was associated with HPV vaccine intentions above and beyond the effects of HBM variables among men. Among women, neither anticipated regret nor HBM variables showed consistent associations with HPV vaccine intentions. Findings suggest that anticipatory emotions should be considered when designing interventions to increase HPV vaccination among college men.     

Factors influencing the reproductive decision after genetic counseling

Here we report a follow-up study involving interviews with 164 couples 2-3 years after genetic counseling to assess the influence of various factors on their reproductive planning. The results show that the desire to have children and the absence of personal experience with the disorder (no close relative being affected) are important single factors for the decision to opt for having children after genetic counseling. The magnitude of the genetic risk is of relative importance in reproductive planning. Seventy percent of the couples with a high genetic risk (greater than 15%) opted for having children. When the disorder was perceived as severe and the risk was interpreted as high, 72% opted for having children. The availability of prenatal diagnosis became important only in combination with a high genetic risk (greater than 15%). Forty-seven percent of the couples with a high genetic risk refrained from having children when prenatal diagnosis was not available. In the absence of prenatal diagnosis, couples who had an affected child were more cautious about trying again than those who did not--50% versus 14% decided to abstain. This study has provided some insight into the complexity of reproductive decision-making after genetic counseling. The findings may help genetic counselors and clinical geneticists understand and support counselees in their decision-making process, which is "multi-factorial."     

Monozygotic twins discordant for 18q21.2qter deletion detected by array CGH in amniotic fluid

Discordant chromosomal anomalies in monozygotic twins may be caused by various timing issues of erroneous mitosis and twinning events. Here, we report a prenatal diagnosis of heterokaryotypic monozygotic twins discordant for phenotype. In a 28-year-old woman, ultrasound examination performed at 26 weeks of gestation, detected intrauterine growth restriction and unilateral cleft lip and palate in twin B, whereas twin A had normal fluid, growth and anatomy. Molecular karyotyping in twin B identified a 18q21.2qter deletion, further confirmed by FISH analysis on amniocytes. Interestingly, in twin A, cytogenetic studies (FISH analysis and karyotype) on amniocytes were normal. Genotyping with microsatellite markers confirmed the monozygosity of the twins. At 32 weeks of gestation, selective termination of twin B was performed by umbilical cord coagulation and fetal blood samples were taken from the umbilical cord in both twins. FISH analyses detected mosaicism in both twins with 75% of cells being normal and 25% harboring the 18qter deletion. After genetic counseling, the parents elected to terminate the second twin at 36 weeks of gestation. In postmortem studies, FISH analyses revealed mosaicism on several tissues in both twins. Taking into account this observation, we discuss the difficulties of genetic counseling and management concerning heterokaryotypic monozygotic twins.     

Decision to abort after a prenatal diagnosis of sex chromosome abnormality: a systematic review of the literature

We performed a systematic review of factors affecting parental decisions to continue or terminate a pregnancy after prenatal diagnosis of a sex chromosome abnormality, as reported in published studies from 1987 to May 2011. Based on the Matrix Method for systematic reviews, 19 studies were found in five electronic databases, meeting specific inclusion/exclusion criteria. Abstracted data were organized in a matrix. Alongside the search for factors influencing parental decisions, each study was judged on its methodological quality and assigned a methodological quality score. Decisions either to terminate or to continue a sex chromosome abnormality-affected pregnancy shared five similar factors: specific type of sex chromosome abnormality, gestational week at diagnosis, parents' age, providers' genetic expertise, and number of children/desire for (more) children. Factors unique to termination decisions included parents' fear/anxiety and directive counseling. Factors uniquely associated with continuation decisions were parents' socioeconomic status and ethnicity. The studies' average methodological quality score was 10.6 (SD = 1.67; range, 8-14). Findings from this review can be useful in adapting and modifying guidelines for genetic counseling after prenatal diagnosis of a sex chromosome abnormality. Moreover, improving the quality of future studies on this topic may allow clearer understanding of the most influential factors affecting parental decisions.     

Impact of PKU on the reproductive patterns in collaborative study families

Factors that relate to reproductive patterns in 129 families after the birth of a child with phenylketonuria (PKU) include birth order of the index child, age of the parents at the birth of the index child, and expressed intentions of the parents whether or not to have additional children. Factors that do not correlate with reproductive histories include knowledge of the genetic and metabolic nature of PKU, the relationship of PKU to mental retardation and special diet, parental upset about the diagnosis, sex of the affected child, parental IQ, religion, education, and social class. Correlations found related to the question, "Is PKU the reason you don't want more children?" include stress factors in family functioning, mother's upset with the diagnosis, father's concerns about being a carrier, sex of the child with PKU, and degree of knowledge about PKU. Many of the Collaborative Study clinics tend to be more concerned about the consequences of PKU on the family than on society, and feel that families should receive genetic counseling to determine their reproductive risks and future plans. Upon self-report, many clinics declare their counseling to be either "completely nondirective" or making a "conscious effort to be nondirective."     

一例由染色体不平衡易位t(5;15)导致的Prader-Willi综合征

目的 对1例临床疑似Prader-willi综合征(Prader-Wil syndrome,PWS)的患儿进行遗传学诊断和分型.方法 应用染色体核型分析结合甲基化特异性PCR(methylation-specific PCR,MS-PCR)及短串联重复序列(short tandem repeat,STR)家系连锁分析方法对患儿进行诊断和分子病理学分型.结果 患儿染色体核型为45,XX,der(5)t(5;15)(q35;q13),-15,存在5号与15号染色体之间的不平衡易位;甲基化特异性PCR及STR家系连锁分析方法进一步证实患儿为父源15号染色体不平衡易位导致的15q缺失型Prader-Willi综合征.结论 临床疑似PWS的患儿应进行遗传学检查,以便获得确诊.细胞遗传学及分子遗传学方法的有效结合对于临床诊断、分辨不同病理类型、遗传咨询以及产前诊断都具有积极的作用.     

Reproductive decision making of aunts and uncles of a child with cystic fibrosis: genetic risk perception and attitudes toward carrier identification and prenatal diagnosis.

This paper evaluates the perceived genetic risk, the perceived burden, the impact on reproductive decision making, and the attitudes of aunts and uncles of a child with cystic fibrosis toward carrier identification, prenatal diagnosis, and pregnancy termination. A mailed questionnaire was sent to the aunts and uncles of 32 CF children (1) who attended the Paediatric Department of the University Hospital and (2) whose parents agreed to give the names and addresses of their sibs. The results for the 109 respondents aged less than 40 years are discussed. About one-fourth of them was aware of the "approximate" level of the risk to be a carrier of the CF gene and/or of the risk of having a CF child themselves. Nevertheless the subjective evaluation of the genetic risk has played a part in the reproductive decision-making process of at least 39% of the respondents. About three-fourths would (probably) make use of heterozygote detection and would (probably) ask for prenatal diagnosis should they become pregnant. It is striking that less than half of the group would interrupt the pregnancy should the fetus be affected. The intention to use prenatal diagnosis was significantly correlated with age and educational level while the acceptance of pregnancy interruption was significantly correlated with perceived burden, respondents' age, and health situation of the proband.     

Psychological response to prenatal genetic counseling and amniocentesis

The purpose of the present study was to characterize the psychological status (attitudes toward selective abortion, perceived risk, comprehension, patient satisfaction, coping, and state anxiety) of pregnant women at increased risk for fetal genetic anomalies who were referred for prenatal genetic counseling and amniocentesis; to determine which of these factors would predict amniocentesis use; and to identify patient outcomes associated with counseling and testing. Participants were 129 women aged 18 years and older who had one or more fetal genetic risk factors. All were recruited from an urban women's health clinic. The results revealed elevated perceptions of risk and moderate state anxiety despite adequate comprehension of, and patient satisfaction with, the process and content of genetic counseling. Approximately 78% agreed to testing; those who consented were more likely to hold favorable attitudes toward abortion than those who refused. Post-counseling, women experienced decrease in their perceived risk of having a baby born with a birth defect although perceived risk estimates remained higher than actual risks. Anxiety was clinically elevated and highest at the pre-counseling stage, though it dissipated to normal levels over time. Previous experience with prenatal diagnostic testing, increased perceived risk of a birth anomaly, and favorable attitudes toward abortion were independently associated with increased pre-counseling anxiety. Women who were more anxious pre-counseling remained more anxious post-counseling. Coping (high versus low monitoring) was unrelated to anxiety. These findings suggest that women who participate in prenatal counseling and testing may be subject to experience distress and unrealistic perceptions of their risk and may benefit from interventions designed to lessen these states.     

Factors associated with preimplantation genetic diagnosis acceptance among women concerned about hereditary breast and ovarian cancer

PurposeTo assess sociodemographic, clinical, awareness, and attitudinal factors associated with acceptance of preimplantation genetic diagnosis among women concerned about hereditary breast and ovarian cancer.MethodsParticipants (n = 962) were members of a national advocacy organization dedicated to empowering women at high risk for developing breast or ovarian cancer. Participants completed a web-based survey assessing factors associated with preimplantation genetic diagnosis acceptance. Factors significantly associated with acceptance in the bivariate analyses were used to build a logistic regression model.ResultsAmong the 962 respondents, 318 (33.1%) selected the option that they would consider preimplantation genetic diagnosis, 367 (38.2%) would not consider preimplantation genetic diagnosis, and 277 (28.8%) selected “don't know.” Significant predictors of preimplantation genetic diagnosis acceptance were the desire to have more children, having had a prenatal genetic test, preimplantation genetic diagnosis awareness, belief that preimplantation genetic diagnosis is acceptable for individuals at risk for hereditary breast and ovarian cancer, belief that preimplantation genetic diagnosis information should be given to individuals at risk for hereditary breast and ovarian cancer, concerns about preimplantation genetic diagnosis, perceived benefits of preimplantation genetic diagnosis, and how preimplantation genetic diagnosis is considered.ConclusionWomen at increased risk for hereditary cancer may consider preimplantation genetic diagnosis as part of their reproductive decision making. Therefore, it is important to understand existing levels of awareness and attitudes toward this technology to provide optimal counseling and support.     

Prenatal diagnosis of a de novo ring chromosome 11

Ring chromosomes are uncommon findings in prenatal diagnosis. Growth retardation is the most significant manifestation, in particular among patients with rings of larger chromosomes. A 30-year-old gravida 1, para 0 white woman was referred for genetic counseling because of maternal anxiety. Cytogenetic analysis of amniotic fluid cells at 16 weeks gestation revealed an abnormal mosaic female chromosome complement; 46,XX,r(11)(p15q25)[14]/45,XX,-11[7]. The ring 11 showed no detectable loss of chromosomal material at 450 band level. Both parents had a normal karyotype. Fluorescence in situ hybridization demonstrated intact subtelomeric regions in the ring chromosome. A targeted ultrasound evaluation at the time of consultation suggested no significant abnormalities. The parents were counseled and subsequently decided to terminate the pregnancy. The autopsy revealed an immature female fetus with abnormal craniofacial features including brachycephaly, low-set ears and hypertelorism, bicornuate uterus, and calcifications in the renal tubules. The abnormal phenotypes could be a consequence of the ring instability, submicroscopic deletion, and/or alteration of genetic material at the site of fusion.     

Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management

PurposeUnexpected fetal abnormalities occur in 2–5% of pregnancies. While traditional cytogenetic and microarray approaches achieve diagnosis in around 40% of cases, lack of diagnosis in others impedes parental counseling, informed decision making, and pregnancy management. Postnatally exome sequencing yields high diagnostic rates, but relies on careful phenotyping to interpret genotype results. Here we used a multidisciplinary approach to explore the utility of rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as an exemplar.MethodsParents in pregnancies undergoing invasive testing because of sonographic fetal abnormalities, where multidisciplinary review considered skeletal dysplasia a likely etiology, were consented for exome trio sequencing (both parents and fetus). Variant interpretation focused on a virtual panel of 240 genes known to cause skeletal dysplasias.ResultsDefinitive molecular diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings alone were of sufficient severity for parents to opt for termination. In others, molecular diagnosis informed accurate prediction of outcome, improved parental counseling, and enabled parents to terminate or continue the pregnancy with certainty.ConclusionTrio sequencing with expert multidisciplinary review for case selection and data interpretation yields timely, high diagnostic rates in fetuses presenting with unexpected skeletal abnormalities. This improves parental counseling and pregnancy management.     

Prenatal diagnosis of micrognathia in 41 fetuses: Retrospective analysis of outcome and genetic etiologies

Fetal micrognathia can be detected early in pregnancy. Prognosis of micrognathia depends on the risk of respiratory distress at birth and on the long‐term risk of intellectual disability. The purpose of this study was to evaluate the long‐term prognosis of fetuses with prenatal diagnosis of micrognathia by estimating the prevalence and the severity of confirmed genetic diagnosis in our cohort. Our retrospective study included 41 fetuses with prenatal diagnosis of micrognathia referred to the multidisciplinary centers for prenatal diagnosis in Nice and Marseille, France, between 2006 and 2016. Fetal micrognathia was associated with cleft palate in 27 cases. A genetic cause was confirmed in 21 cases (67%). A chromosomal abnormality was present in 12 cases, including three copy‐number variations diagnosed by array CGH. Monogenic disorders were identified in nine cases, most often after birth. Fetuses with family history of micrognathia or Pierre Robin sequence had a favorable outcome. Prognosis was good for the fetuses without associated findings and normal chromosomal analysis, with the exception of one case with a postnatal diagnosis of mandibulofacial dysostosis with microcephaly. Prognostic was poor for the fetuses with additional ultrasound anomalies, as only 5 out of 28 children had a good outcome. Prenatal diagnosis of micrognathia is an indicator of a possible fetal pathology justifying multidisciplinary management. Our study confirms the necessity of performing prenatal array CGH. Use of high‐throughput gene sequencing in prenatal period could improve diagnostic performance, prenatal counseling, and adequate postnatal care.     

Uncertainty and perceived personal control among parents of children with rare chromosome conditions: the role of genetic counseling

Little is known about the impact of genetic counseling on parental uncertainty or perceived control regarding the prognosis of a child with a chromosomal disorder. By exploring the parents' concerns and needs surrounding the child's diagnosis, a genetic provider can help to facilitate effective coping. This study tested the association of measures of parental uncertainty and perceived control with the perceived helpfulness of the genetic counselor. A survey was distributed to 875 members of the Chromosome Deletion Outreach (CDO) support group. We hypothesized that parents' perceptions about the helpfulness of the genetic counselor would modify the relationship between perceived uncertainty, perceived control, and coping. Among the 363 respondents, there was a significant negative correlation of the perceived helpfulness of seeing a genetic counselor with the levels of uncertainty (rs = -0.20, P-value < 0.001). Lower perceived helpfulness of the genetic counselor, along with less perceived personal control, less benefit of a diagnosis, and lower parental age were significant predictors of the highest perceptions of uncertainty. The Transactional Model of Stress and Coping was used as a framework for interpreting the relationships between parental uncertainty, perceived control, and outcome variables. There was a significant positive correlation between parents' perceived personal control and their reports of helpfulness of the genetic counselor (rs = 0.20, P-value <0.0006). Genetic counseling can be enhanced for parents faced with rare disorders by using interventions focused on reducing feelings of uncertainty and enhancing feelings of control.     

Psychological and social determinants of women's decisions to undergo genetic counseling and testing for breast cancer

This study examined the demand for breast cancer genetic testing and counseling among Canadian women diagnosed with breast cancer under the age of 50, together with some of the factors predicting both their intentions to be tested and the degree to which they act on their intentions. Participants were 110 women under the age of 50 and comprised of two groups: 1) women diagnosed with breast cancer (BC, n = 60): and 2) an index group of unaffected women from the general population (GP, n = 50). All participants completed a survey that addressed family history of breast and other cancers, demographic variables, knowledge and attitudes about breast cancer, and genetic testing. Members of the BC group were offered genetic counseling and testing for BRCA1 and BRCA2 free of charge. Overall, 60% of participants indicated they would like the test, and 40% either did not want it or were uncertain. Seventy-two percent of women in the BC group wanted to be tested. Of these, only 49% had actually contacted the genetic counselor about testing at follow-up 3-15 months later. Intention to be tested was associated with presence of breast cancer, greater perceived benefits of testing, fewer perceived 'costs' of testing, and higher levels of concern about the risk of relatives developing breast cancer. Actual arranging to meet with the genetic counselor among women in the BC group was associated with fewer perceived costs of having the test. Results suggest a moderate level of interest in gene testing, though intention to be tested may not translate into actual uptake. Women who do choose to have the test may believe the potential 'costs' of using this new genetic technology to be relatively few. This has implications for genetic counselors in terms of providing balanced and complete information to women considering genetic testing for breast cancer susceptibility.     

Development of instruments to measure counselees'' knowledge of Down syndrome

Since approximately 10% of counselees coming to genetics clinics are concerned with Down syndrome, the development of short measures of knowledge of Down syndrome for evaluation could have widespread application. The purpose of this study was to design efficient, self-administered questionnaires of simple vocabulary to measure knowledge and understanding of Down syndrome before and after genetic counseling. Twenty-six previously piloted questions were administered to nurses, graduate students in Medical Genetics, special education teachers, and parents of children with Down syndrome (n = 126). A coefficient alpha of 0.842 indicated strong reliability. The content of the questionnaire was distributed into three categories: genetic knowledge, recurrence risk, and prenatal diagnosis. From the items (1) which had less than 85% correct responses, and (2) which fell into just one of the three categories, 12 questions were selected as a post-test (coefficient alpha of 0.749). Eight additional questions were then extracted (coefficient alpha of 0.56) as a pretest. The pretest predicted 53.3% of the variance of the post-test. The use of these instruments before and after counseling can be an aid in evaluating counseling and in comparing various approaches for effectiveness.     

Parents’ understanding of genome and exome sequencing for pediatric health conditions: a systematic review

Genome and exome sequencing (GS/ES) are increasingly being used in pediatric contexts. We summarize evidence regarding the actual and perceived understanding of GS/ES of parents of a child offered testing for diagnosis and/or management of a symptomatic health condition. We searched four databases (2008–2021) and identified 1264 unique articles, of which 16 met inclusion criteria. We synthesized data from qualitative and quantitative studies and organized results using Ayuso et al. (2013)’s framework of key elements of information for informed consent to GS/ES. Many of the parents represented had prior experience with genetic testing and accessed a form of genetic counseling. Parents’ understanding was varied across the domains evaluated. Parents demonstrated understanding of the various potential direct clinical benefits to their child undergoing GS/ES, including in relation to other genetic tests. We found parents had mixed understanding of the nature of potential secondary findings, and of issues related to data privacy, confidentiality, and usage of sequencing results beyond their child’s clinical care. Genetic counseling consultations improved understanding. Our synthesis indicates that ES/GS can be challenging for families to understand and underscores the importance of equipping healthcare professionals to explore parents’ understanding of ES/GS and the implications of testing for their child.Subject terms: Patient education, Paediatrics