Genetic Testing of Children at Risk for Adult Onset Conditions: When is Testing Indicated?

We report a family with an extensive history of colon cancer consistent with hereditary nonpolyposis colorectal cancer (HNPCC). A specific disease causing mutation was identified in affected individuals; p.W714X MLH1 mutation. Given the very young age of onset of cancer in some affected family members, with the youngest affected individual being 19 years of age, genetic counseling was recommended to children as young as 9 years. Ethical issues arose when affected families requested genetic testing for their underage children. Here we describe and debate the value of offering molecular testing for this adult onset disorder to several children in this particular family. We also examine possible molecular causes for the very young age of onset in some family members.     

Men’s Decision-Making About Predictive <Emphasis Type="Italic">BRCA1/2</Emphasis> Testing: The Role of Family

Men who have a family history of breast and/or ovarian cancer may be offered a predictive genetic test to determine whether or not they carry the family specific BRCA1/2 mutation. Male carriers may be at increased risk of breast and prostate cancers. Relatively little is known about at-risk men’s decision-making about BRCA1/2 testing. This qualitative study explores the influences on male patients’ genetic test decisions. Twenty-nine in-depth interviews were undertaken with both carrier and noncarrier men and immediate family members (17 male patients, 8 female partners, and 4 adult children). These explored family members’ experiences of cancer and genetic testing, decision-making about testing, family support, communication of test results within the family, risk perception and risk management. Implicit influences on men’s testing decisions such as familial obligations are examined. The extent to which other family members—partners and adult children—were involved in testing decisions is also described. It is demonstrated that mothers of potential mutation carriers not only perceive themselves as having a right to be involved in making this decision, but also were perceived by their male partners as having a legitimate role to play in decision-making. There was evidence that (adult) children were excluded from the decision-making, and some expressed resentment about this. The implications of these findings for the practice of genetic counseling are discussed.     

Return of Genetic Results in the Familial Dilated Cardiomyopathy Research Project

The goal of the Familial Dilated Cardiomyopathy (FDC) Research Project, initiated in 1993, has been to identify and characterize FDC genetic cause. All participating individuals have been consented for the return of genetic results, an important but challenging undertaking. Since the inception of the Project we have enrolled 606 probands, and 269 of these had 1670 family members also enrolled. Each subject was evaluated for idiopathic dilated cardiomyopathy (IDC) and pedigrees were categorized as familial or sporadic. The coding regions of 14 genes were resequenced in 311 to 324 probands in five studies. Ninety-two probands were found to carry nonsynonymous rare variants absent in controls, and with Clinical Laboratory Improvement Amendment of 1988 (CLIA) compliant protocols, relevant genetic results were returned to these probands and their consented relatives by study genetic counselors and physicians in 353 letters. In 10 of the 51 families that received results >1 year ago, at least 23 individuals underwent CLIA confirmation testing for their family’s rare variant. Return of genetic results has been successfully undertaken in the FDC Research Project. This report describes the methods utilized in the process of returning research results. We use this information as a springboard for providing guidance to other genetic research groups and proposing future directions in this arena.     

IQ correlations in transracial adoptive families

IQ tests were administered to all available members over 4 years old in 101 transracial adoptive families when the adopted children were an average of 7 years old and again when they averaged 17 years old. At both times, 426 members of 93 families were studied; 398 were seen in person and administered the WAIS-R or WISC-R. IQ correlations were calculated for adopted and biological parent-child pairs, and for genetically related and unrelated siblings. Educational levels of birth parents were correlated with the IQ scores of their adopted-away children. Results show that biologically related family members tended to resemble each other intellectually more than did adoptive family members at both time points. IQ correlations for biological parent-child pairs exceeded those for adoptive parent-child pairs, and correlations were greater for genetically related than unrelated siblings. In late adolescence, the IQ scores of unrelated siblings in the transracial adoptive families were more similar than those of unrelated adolescent siblings pairs reported in other studies. The pattern of IQ correlations for unrelated siblings suggested that familial environmental influences on IQ decline from childhood to late adolescence, but this conclusion was not supported by parent-child IQ correlations. The effects of selective placement on familial IQ correlations were small. Estimates of genetic and familial environmental influences on IQ were very similar to those of other studies. This suggests that the influences on intellectual development in this sample of black/interracial adoptees reared in white families are similar to those for children in the majority populations of the United States and Western Europe.     

The Familial Cancer Program of the Vermont Cancer Center: Development of a Cancer Genetics Program in a Rural Area

In response to many scientific discoveries linking cancer in certain families to inherited factors, the Vermont Cancer Center established the Familial Cancer Program (FCP) in December 1993. This multifaceted program combines the expertise of clinicians and researchers in many disciplines, including genetics, oncology, psychology, and molecular biology. The program's goals are identification of families in its region with excess cancer, provision of clinical services to such families, and use of research protocols when available and appropriate. This article describes the experience of setting up a familial cancer program in a rural area and discusses both successes and challenges in such an endeavor.     

Familial influences on television viewing and aggression: A sibling study

Familial influences on aggressive behavior and TV viewing were investigated in a survey of adolescent siblings. Same-sex siblings resembled one another in aggression (brothers, r = 0.59; sisters, r = 0.52) and in their exposure to violent TV programs; opposite-sex siblings were dissimilar. Within individuals, the frequency of watching crime and action programs correlated nonsignificantly with aggression. Two other variables, however, were associated with aggression: identification with aggression and aggression consequences. These relationships also held up between families (BF, covariance of sibling' averages) and within families (WF, covariance of sibling' differences). The latter WF relationship indicated that one sibling was typically the more extreme on both aggression and its correlate than a brother or sister. These results were interpreted in light of behavioral genetic data that suggest substantial genetic influences, few common environmental influences, and large within-family environmental influences on personality development.     

Testicular Cancer and Genetics Knowledge Among Familial Testicular Cancer Family Members

Purpose  

It was our aim to determine baseline levels of testicular cancer and genetics knowledge among members of families with Familial Testicular Cancer (FTC).     

Cancer Risk Assessment and Genetic Counseling in an Academic Medical Center: Consultands' Satisfaction, Knowledge, and Behavior in the First Year

In 1995, we formally established a multifaceted cancer genetics program of clinical services, research, and education at a general academic medical center. In the first year, 58 families, mostly physician referred, received cancer risk assessment and genetic counseling for a family and/or medical history of cancer. The primary reasons for seeking consultation were to determine their risk or their offspring's risk for developing certain cancers and to inquire about the availability of DNA testing for predisposition to breast, ovarian, or colon cancers. To assess the level of satisfaction with program services, 51 consultands (22% with a personal history of cancer) were interviewed independently by telephone 3–12 months after the session. One goal of the survey was to improve program service. Ninety percent of respondents reported that the consultation was worth their time and money. Forty-two percent stated that their anxiety related to their cancer risk had decreased following counseling and 56% indicated no change. Recall of exact numerical risk was poor and one-third could not remember hearing any risk estimate. More respondents would recommend the service to friends (90%) than to family members (75%). Overall, the service was positively received by the majority of patients.     

Parental Attitudes,Beliefs, and Perceptions about Genetic Testing for FAP and Colorectal Cancer Surveillance in Minors

Familial adenomatous polyposis (FAP) is the second most common hereditary colorectal cancer syndrome and confers a nearly 100% lifetime risk of developing colorectal cancer. Understanding factors that facilitate and inhibit genetic testing and cancer surveillance in children who are members of families affected by FAP will better equip clinicians to clarify misunderstandings and facilitate appropriate care. The aims of this study were to examine parental attitudes and beliefs regarding endoscopic surveillance and genetic testing in minors at risk for developing FAP. This cross-sectional study includes analyses of qualitative and quantitative interview data collected from parents of children with or at risk for FAP. This report includes data from 28 parents with a total of 51 biological children between 10–17 years of age. The parents had a clinical and/or genetic diagnosis of FAP. Most commonly reported facilitators included provider recommendation (surveillance) and personalized medical management (genetic testing). Most commonly reported barriers included lack of provider recommendation (surveillance) and cost (genetic testing).     

Understanding responses to predictive genetic testing: A grounded theory approach

Abstract

In view of the absence of data concerning the understanding and experience of families in which one or more members have undergone predictive genetic testing, a pilot study using a qualitative methodology was conducted with members of families at risk for the late-onset genetic disease, familial adenomatous polyposis (FAP). Semistructured interviews were conducted to elicit illness representations, with responses tape-recorded and analysed using a grounded theory approach. Several themes emerged. The most striking was that when genetic testing indicated an extremely low risk of developing the disease, there was a desire to continue regular bowel screening, even though it was experienced as extremely aversive. Possible explanations draw upon both other themes of the interviews, and psychological models. The role of “functional pessimism” and “uncertain wellness” in maintaining a high threat from the disease, and the role of reinforcement and the nature of tests in providing bowel screening with a high value are discussed.     

“I Wouldn’t Classify Myself as a Patient”: The Importance of a “Well-being” Environment for Individuals Receiving Counseling about Familial Cancer Risk

Many individuals receiving genetic counseling are healthy with no need for clinical cancer services. We have recently relocated our cancer genetic clinic to a small house on the outskirts of a hospital site which incorporates many elements proven to be important in creating a “well-being” environment. This study explored participants’ perceptions of such an environment. Eleven semi-structured telephone interviews were conducted with women who had attended the new cancer genetic clinic. All were at high risk of familial cancer, five were gene carriers and three had a personal diagnosis of cancer. The new clinic was perceived to be less medical and more relaxing than other clinics, encouraged other family members to attend in support of the attendee and did not appear to impede information comprehension. The importance of not being made to feel like an ill patient was apparent. A desire for a quiet area allowing time for reflection whilst waiting for, and following, counseling was identified. A poorly designed counseling area could reduce the quality of the interaction between patient and counselor. Consideration of specific environmental design features may promote individuals’ well-being and make those attending genetic counseling feel less like “patients.” Larger studies should seek to explore further the potential associations between factors such as environmental design, psychological well-being and comprehension of risk information.     

Genetic Counseling and Screening Issues in Familial Dilated Cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC), a treatable condition characterized by left ventricular dilatation and systolic dysfunction of unknown cause, has only recently been recognized to have genetic etiologies. Although familial dilated cardiomyopathy (FDC) was thought to be infrequent, it is now believed that 30-50% of cases of IDC may be familial. Echocardiographic and electrocardiographic (ECG) screening of first-degree relatives of individuals with IDC and FDC is indicated because detection and treatment are possible prior to the onset of advanced, symptomatic disease. However, such screening often creates uncertainty and anxiety surrounding the significance of the results. Furthermore, FDC demonstrates incomplete penetrance, variable expression, and significant locus and allelic heterogeneity, making genetic counseling complex. The provision of genetic counseling for IDC and FDC will require collaboration between cardiologists and genetics professionals, and may also improve the recognition of FDC, the availability of support services, and overall outcomes for patients and families.     

Breast Cancer Risk Perceptions among Relatives of Women with Uninformative Negative <Emphasis Type="Italic">BRCA1/2</Emphasis> Test Results: The Moderating Effect of the Amount of Shared Information

The most common result of BRCA1/2 mutation testing when performed in a family without a previously identified mutation is an uninformative negative test result. Women in these families may have an increased risk for breast cancer because of mutations in non-BRCA breast cancer predisposition genes, including moderate- or low-risk genes, or shared environmental factors. Genetic counselors often encourage counselees to share information with family members, however it is unclear how much information counselees share and the impact that shared information may have on accuracy of risk perception in family members. We evaluated 85 sisters and daughters of women who received uninformative negative BRCA1/2 results. We measured accuracy of risk perception using a latent variable model where accuracy was represented as the correlation between perceived risk (indicators = verbal and quantitative measures) and calculated risk (indicators = Claus and BRCAPRO). Participants who reported more information was shared with them by their sister or mother about her genetic counseling session had greater accuracy of risk perception (0.707, p?=?0.000) than those who reported little information was shared (0.326, p?=?0.003). However, counselees shared very little information; nearly 20 % of family members reported their sister or mother shared nothing with them about her genetic counseling. Family members were generally not aware of the existence of a genetic counseling summary letter. Our findings underscore the need for effective strategies that facilitate counselees to share information about their genetic counseling sessions. Such communication may help their relatives better understand their cancer risks and enhance risk appropriate cancer prevention.     

A Multivariate Genetic Analysis of Specific Phobia, Separation Anxiety and Social Phobia in Early Childhood

BACKGROUND: Comorbidity amongst anxiety disorders is very common in children as in adults and leads to considerable distress and impairment, yet is poorly understood. Multivariate genetic analyses can shed light on the origins of this comorbidity by revealing whether genetic or environmental risks for one disorder also influence another. We examined the genetic and environmental influences on the comorbidity between three common childhood anxiety disorders: Specific Phobia, Separation Anxiety and Social Phobia. METHODS: Using a two-phase design 4,662 twin-pairs were screened in the first phase and 854 pairs were assessed in the second phase by maternal-informant diagnostic interview using DSM-IV criteria. RESULTS: Multivariate genetic analysis revealed significant shared environmental over-lap between Specific Phobia and Separation Anxiety and significant familial and non-shared environmental over-lap between Specific Phobia and Social Phobia. CONCLUSIONS: Familial influences, especially shared environment, are central to the comorbidity between Specific Phobia and both Separation Anxiety and Social Phobia.     

Stigma by Association Among Family Members of People with a Mental Illness: A Qualitative Analysis

People with mental illness are not the sole recipients of stigmatisation; their immediate family members may be subjected to stigma by association. Through semi‐structured interviews, we investigated experiences of stigma by association among 23 immediate family members of people with mental illness. Participants reported experiencing stigma by association from community members, mental health professionals, and civil servants. Familial relationship, co‐residence, and the gender of participants appeared to play a role in their stigma experiences; parents and spouses reported different manifestations of stigma by association than siblings and children, participants who lived together with their family member with mental illness reported increased experiences of stigma by association, and in contrast to male participants, female participants reported others thinking they are overprotective and as such perpetuated, maintained, or sustained their family members' mental illness. The relevance of these factors points to the need for tailored education and emotional support provision to family members of people with mental illness. Moreover, in‐service training for mental health professionals should include the development of relevant social skills that enable the recognition of familial relationships and roles, and family members' fears, concerns, and problems. Copyright © 2014 John Wiley & Sons, Ltd.     

结直肠转移癌临床表现与治疗

为了探讨结直肠癌转移的临床特点,对我院于2000年1月-2007年12月收治的12例结肠转移癌患者的诊疗及预后进行了回顾性分析。结果显示,12例结肠转移癌患者,原发肿瘤分别来源于胃癌5例,肺癌3例,乳腺癌2例,胰腺癌1例,胆囊癌1例,提示结肠转移癌在临床上并不多见,提示患者已经出现广泛转移且预后不良。     

Cancer Worry,Perceived Risk and Cancer Screening in First-Degree Relatives of Patients with Familial Gastric Cancer

Currently, there is a lack of evidence evaluating the psychological impact of cancer-related risk perception and worry in individuals at high risk for gastric cancer. We examined the relationships between perceived risk, cancer worry and screening behaviors among first-degree relatives (FDRs) of patients with familial gastric cancer. FDRs of patients diagnosed with familial gastric cancer with a non-informative genetic analysis were identified and contacted. Participants completed a telephone interview that assessed socio-demographic information, cancer risk perception, cancer worry, impact of worry on daily functioning, and screening behaviors. Twenty-five FDRs completed the telephone interview. Participants reported high levels of comparative and absolute cancer risk perception, with an average perceived lifetime risk of 54 %. On the other hand, cancer-related worry scores were low, with a significant minority (12 %) experiencing high levels of worry. Study participants exhibited high levels of confidence (median = 70 %) in the effectiveness of screening at detecting a curable cancer. Participants that had undergone screening in the past showed significantly lower levels of cancer-related worry compared to those that had never undergone screening. In conclusion, individuals at high-risk for gastric cancer perceived a very high personal risk of cancer, but reported low levels of cancer worry. This paradoxical result may be attributed to participants’ high levels of confidence in the effectiveness of screening. These findings highlight the importance for clinicians to discuss realistic risk appraisals and expectations towards screening with unaffected members of families at risk for gastric cancer, in an effort to help mitigate anxiety and help with coping.     

Multivariate Familial Analysis of Cognitive Measures in the Colorado Family Reading Study

Multivariate path analysis is employed to examine the etiologies of variation and covariation of three composite cognitive measures in the Colorado Family Reading Study: reading ability, symbol-processing speed, and spatial/reasoning. Measures of phenotypic assortative and cross-assortative mating are incorporated in a multivariate analysis of familial resemblance within nuclear families. Phenotypic variances and covariances are partitioned into components due to familial (genetic and/or family environmental) influences and to specific, nontransmissible environmental influences in families with a reading-disabled child as well as families with children of normal reading ability. Comparable moderate familial influences are found across family type for all three composites and the phenotypic correlations between traits are largely due to familial influences.     

Predicting delayed letter knowledge development and its relation to grade 1 reading achievement among children with and without familial risk for dyslexia

The authors examined the developmental trajectories of children's early letter knowledge in relation to measures spanning and encompassing their prior language-related and cognitive measures and environmental factors and their subsequent Grade 1 reading achievement. Letter knowledge was assessed longitudinally at ages 4.5, 5.0, 5.5, and 6.5 years; earlier language skills and environmental factors were assessed at ages 3.5 and 4.5 years; and reading achievement was assessed at the beginning and end of Grade 1. The analyses were conducted on a longitudinal data set involving children with and without familial risk for dyslexia. Emerging from the trajectory analysis of letter knowledge were 3 separate clusters: delayed (n = 63), linearly growing (n = 73), and precocious (n = 51). The members of the delayed cluster were predominantly children with familial risk for dyslexia, and the members of the precocious cluster were predominantly control group children. Phonological sensitivity, phonological memory, and rapid naming skills predicted delayed letter knowledge. Environmental predictors included level of maternal education and the amount of letter name teaching. Familial risk for dyslexia made a significant contribution to the predictive relations. Membership in the delayed cluster predicted poor reading performance at Grade 1.     

The Relationship Between Psychological Distress and Personality in Women from Families with Familial Breast/Ovarian or Hereditary Non-polyposis Colorectal Cancer in the Absence of Demonstrated Mutations

The aim of this study was to explore associations between mental and cancer-specific distress (psychological distress) and personality traits in healthy women belonging to families with familial cancer and absence of demonstrated mutations. We included 238 healthy women from families with familial breast-ovarian cancer (FBOC) or hereditary non-polyposis colorectal cancer (HNPCC). They responded to a questionnaire including validated instruments for psychological distress and personality traits. Information on demography and cancer-related issues were also collected. Significant associations between psychological distress and personality traits were found in these women. The traits of Optimism and Harm avoidance showed the strongest association with both types of distress. Associations between psychological distress and personality traits were observed in women from families with FBOC or HNPCC that fulfilled clinical criteria for familial breast/ovarian cancer in the absence of demonstrated mutations. Screening for such traits could be helpful in genetic counseling.