Síndrome de Peutz-Jeghers, telangiectasias y prolapso de la válvula mitral. Presentación de caso y asesoramiento genético / Peutz-Jeghers syndrome, telangiectasias, and mitral valve prolapse. Case presentation and genetic counseling

Introducción: El síndrome de Peutz-Jeghers se caracteriza por hiperpigmentación mucocutánea y hamartomas gastrointestinales que pueden aparecer desde el estómago hasta el ano. Tiene un patrón de herencia autosómico dominante y expresividad variable. El diagnóstico se basa en los hallazgos clínicos y la apariencia histológica de los pólipos. No ha sido reportado hasta ahora asociación de esta entidad a telangiectasias y prolapso de la válvula mitral. Objetivo: Describir los hallazgos que permitieron establecer el diagnóstico de Síndrome de Peutz-Jeghers en un paciente y brindar asesoramiento genético. Presentación del caso: Paciente masculino de 36 años de edad con antecedentes de prolapso de la válvula mitral que acude a consulta de genética clínica con su esposa para solicitar asesoramiento genético, debido a que tienen una hija con diagnóstico de Síndrome de Peutz-Jeghers y desean conocer el riesgo de tener otro hijo afectado. Al examen físico se observa mácula hiperpigmentada en labio inferior y varias de estas en encías. Con tales hallazgos y el antecedente de tener la hija Síndrome de Peutz-Jeghers se emite el mismo diagnóstico en el padre. Como dato de interés se constatan en este individuo múltiples telangiectasias en tórax, cuello y espalda. Los estudios realizados en busca de la causa de estas fueron negativos. Conclusiones: Los antecedentes y los hallazgos encontrados en el paciente permitieron realizar el diagnóstico de Peutz-Jeghers y brindar asesoramiento genético. Se presenta el primer reporte de esta enfermedad asociada a telangiectasias y prolapso de la válvula mitral en la literatura científica(AU)

Introduction: Peutz-Jeghers syndrome is characterized by mucocutaneous hyperpigmentation and gastrointestinal hamartomas that can appear from the stomach to the anus. It has an autosomal dominant inheritance pattern and variable expressiveness. The diagnosis is based on clinical findings and histological appearance of the polyps. No association between this entity and telangiectasias and mitral valve prolapse has been reported so far. Objective: To describe the findings that made it possible to establish the diagnosis of Peutz-Jeghers syndrome in a patient and to provide genetic counseling. Case presentation: Thirty-six-year-old male patient with a history of mitral valve prolapse who attends a clinical genetics consultation with his wife to request genetic counseling due to the fact that their daughter was diagnosed with Peutz-Jeghers Syndrome and they want to know about the risk of having another affected child. On physical examination, a hyperpigmented macule on the lower lip and several of these on the gums were observed. With such findings and the antecedent of having a daughter with Peutz-Jeghers syndrome, the same diagnosis is made in the father. As data of interest, multiple telangiectasias on the thorax, neck and back were found in this individual. The studies carried out to identify the same cause were negative. Conclusions: The history and findings in this patient allowed us to make the diagnosis of Peutz-Jeghers syndrome as well as to provide genetic counselling. The first report of this disease associated with telangiectasias and mitral valve prolapse is presented in the scientific literature(AU)

The role of the genetic testing industry in patient education of hereditary cancer: An observational study assessing the quality of patient education videos.

OBJECTIVES: Genetic testing (GT) companies have developed patient education videos to supplement or replace pre-test genetic counseling (GC) by certified genetic counselors (CGC). The aim of this study was to assess the quality of these videos compared to the standard of care (SOC). METHODS: Videos from four major GT companies were selected from an internet search identifying pre-test patient education videos. A scoring rubric with 22 questions and 36 total points was devised to assess quality metrics, as described by the National Cancer Institute and National Society of Genetic Counselors. Twenty-two individuals with varying genetics expertise (3 gynecologic oncologists, 3 academic generalists, 4 CGC, a genetics community health worker, 3 cancer care navigators, and 8 medical students) scored each video. Scorers were blinded to others' assessments. RESULTS: Invitae had the highest median score (26/36), followed by Myriad (22/36), Ambry (17.5/36), and Color (15/36). All videos scored highly in explaining DNA basics, cancer development, and hereditary cancer predisposition. All addressed benefits of GT but failed to address potential disadvantages. All scored poorly in explaining medical terms and different GT options. There was variability in addressing patient concerns including cost, privacy, and procedure. CONCLUSIONS: There is significant variation in the content of pre-test patient education videos between GT companies. None of the videos met the SOC for pre-test GC, and none addressed disadvantages of GT, possibly due to a conflict of interest. With improvement in content, accessibility, and use of interactive platforms, these videos may serve as an adjunct to in-person pre-test GC.

Chromosomal microarray analysis in prenatal diagnosis: ethical considerations of the Belgian approach.

Detection of genetic aberrations in prenatal samples, obtained through amniocentesis or chorion villus biopsy, is increasingly performed using chromosomal microarray (CMA), a technique that can uncover both aneuploidies and copy number variants throughout the genome. Despite the obvious benefits of CMA, the decision on implementing the technology is complicated by ethical issues concerning variant interpretation and reporting. In Belgium, uniform guidelines were composed and a shared database for prenatal CMA findings was established. This Belgian approach sparks discussion: it is evidence-based, prevents inconsistencies and avoids parental anxiety, but can be considered paternalistic. Here, we reflect on the cultural and moral bases of the Belgian reporting system of prenatally detected variants.

Black Women's Confidence in the Genetic Information Nondiscrimination Act.

Black women at-risk for hereditary breast and ovarian cancer (HBOC) continue to underutilize genetic counseling and testing (GCT). One reason for this disparity is a fear of discrimination from insurance companies if identified as high-risk. The Genetic Information Nondiscrimination Act (GINA) was enacted to protect against this type of discrimination; however, Black women's levels of confidence in this law are unknown. In this descriptive study, we sought to (1) assess Black women's confidence in the GINA law and (2) identify multilevel factors related to their confidence in GINA. Ninety-four Black women at-risk of HBOC completed surveys that assessed intrapersonal, interpersonal, and structural factors. Multiple regression analysis determined factors associated with confidence in GINA. Most women were ≤50 years of age (66.0%) and about half never had a cancer diagnosis (51.1%). Confidence in GINA was moderate (mean = 10.67; standard deviation = 2.54; range = 5-15). Women who valued GCT reported more confidence in GINA (ß = 0.345; CI 0.017 to 0.673; p = 0.040). Lack of confidence in GINA may serve as a barrier to seeking GCT. Efforts to increase the perceived value of GCT among Black women could be benefited by increasing awareness of national efforts towards privacy protections of genetic information.

How Should Decision Aids Be Used During Counseling to Help Patients Who Are "Genetically at Risk"?

People with genetic predispositions to disease are faced with uncertainty about whether, when, and to what extent an illness will actually develop. This prognostic uncertainty, combined with knowledge that preventative interventions (eg, risk-reducing surgeries for familial cancer syndromes) could significantly affect people's lives, renders prevention decisions especially challenging. This article illuminates ethical questions about the use of decision aids for people with genetic predispositions and calls for approaching individual decisions in light of ongoing communication and reflection about a person's life goals and values.

Recontact practices of cancer genetic counselors and an exploration of professional, legal, and ethical duty.

The duty to recontact continues to be revisited in the field of clinical genetics and is currently relevant for cancer genetic counseling given the transition from single-gene to multi-gene panel testing. We recruited cancer genetic counselors through the National Society of Genetic Counselors list-serv to complete an online survey assessing current practices and perspectives regarding recontacting patients about diagnostic genetic tests. Forty-one percent of respondents reported that they have recontacted patients to offer updated (new) diagnostic genetic testing (40/97). A majority (61%, 17/28), of genetic counselors who reported recontact specifically for panel testing indicated that the availability of management recommendations for genes not previously tested routinely was an important factor in the decision to recontact. All respondents who recontacted patients reported "improved patient care" as a perceived benefit. Respondents indicated that recontact is mostly a patient responsibility (49%), followed by a shared responsibility between the provider and patient (43%). Few respondents (2%) reported a uniform ethical duty to recontact patients regarding new and updated testing, while the majority (89%) felt that there was some degree of ethical duty. A greater percentage of those who reported past recontact practices reported intention to recontact in the future (p = 0.001). There is little consensus among the genetic counselor respondents about how to approach the recontacting of patients to offer updated genetic testing.

Preferences for in-person disclosure: Patients declining telephone disclosure characteristics and outcomes in the multicenter Communication Of GENetic Test Results by Telephone study.

Telephone disclosure of cancer genetic test results is noninferior to in-person disclosure. However, how patients who prefer in-person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in-person disclosure of genetic test results. We evaluated preferences for in-person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in-person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer-specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer-specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in-person disclosure in most patients, some patients have a strong preference for in-person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in-person disclosure should be honored when possible.

Companions or patients? The impact of family presence in genetic consultations for inherited breast cancer: Relational autonomy in practice.

As in other areas of medical practice, relatives accompany patients to genetic consultations. However, unlike in other areas, the consultations may be relevant to the relatives' health because they may be at risk of developing the same genetic condition as the patient. The presence of relatives in genetic consultation may affect the decision-making process and it raises questions about the perception of patient autonomy and the way it is practiced in genetics. However, these issues have not been examined in previous empirical studies. This article aims to fill this gap by reporting findings from a qualitative study with clinicians working in the area of inherited breast cancer. The findings indicate that family presence has an impact on the patient's decisions to undergo genetic testing and preventative operations when she is diagnosed as a carrier. The findings further indicate that, unlike in other areas of medical practice, blood relatives who are present in consultations are perceived by clinicians as patients or potential patients, and this in turn increases their involvement in discussions in the consultation room. Finally, the findings indicate that in genetics, a relational approach to autonomy is applied. Decisions are made in a social context, where the relatives' views are heard and taken into account. The findings suggest that the conventional bioethical approach to autonomy, which perceives the decision-making unit as comprising a clinician and an individual patient, is challenged in genetics. The findings thus suggest that bioethicists, lawyers and policy-makers should consider whether this individualistic approach is still valid and applicable.

Ethical considerations for modern molecular pathology.

Molecular pathology is becoming an increasingly important discipline in oncology as molecular tumor characteristics will increasingly determine targeted clinical cancer care. In recent years, many technological advances have taken place that contributed to the development of molecular pathology. However, attention to ethical aspects has been lagging behind as illustrated by the lack of publications or professional guidelines. Existing guidelines or publications on ethical aspects of DNA sequencing are mostly aimed at germline or tumor sequencing in clinical genetics or biomedical research settings. As a result, large differences have been demonstrated in the process of tumor sequencing analysis between laboratories. In this perspective we discuss the ethical issues to consider in molecular pathology by following the process of tumor DNA sequencing analysis from the preanalytical to postanalytical phase. For the successful and responsible use of DNA sequencing in clinical cancer care, several moral requirements must be met, for example, those related to the interpretation and returning of genetic results, informed consent, and the retrospective as well as future use of genetic data for biomedical research. Many ethical issues are new to pathology or more stringent than in current practice because DNA sequencing could yield sensitive and potentially relevant data, such as clinically significant unsolicited findings. The context of molecular pathology is unique and complex, but many issues are similar to those applicable to clinical genetics. As such, existing scholarship in this discipline may be translated to molecular pathology with some adaptations and could serve as a basis for guideline development. For responsible use and further development of clinical cancer care, we recommend that pathologists take responsibility for the adequate use of molecular analyses and be fully aware and capable of dealing with the diverse, complex, and challenging aspects of tumor DNA sequencing, including its ethical issues. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Attitudes of paediatric and obstetric specialists towards prenatal surgery for lethal and non-lethal conditions.

BACKGROUND: While prenatal surgery historically was performed exclusively for lethal conditions, today intrauterine surgery is also performed to decrease postnatal disabilities for non-lethal conditions. We sought to describe physicians' attitudes about prenatal surgery for lethal and non-lethal conditions and to elucidate characteristics associated with these attitudes. METHODS: Survey of 1200 paediatric surgeons, neonatologists and maternal-fetal medicine specialists (MFMs). RESULTS: Of 1176 eligible physicians, 670 (57%) responded (range by specialty, 54%-60%). In the setting of a lethal condition for which prenatal surgery would likely result in the child surviving with a severe disability, most respondents either disagreed (59%) or strongly disagreed (19%) that they would recommend the surgery. Male physicians were twice as likely to recommend surgery for the lethal condition, as were physicians who believe that abortion is morally wrong (OR 1.75; 95%CI 1.0 to 3.05). Older physicians were less likely to recommend surgery (OR 0.57; 95%CI 0.36 to 0.88). For non-lethal conditions, most respondents agreed (66% somewhat, 4% strongly) that they would recommend prenatal surgery, even if the surgery increases the risk of prematurity or fetal death. Compared with MFMs, surgeons were less likely to recommend such surgery, as were physicians not affiliated with a fetal centre, and physicians who were religious (ORs range from 0.45 to 0.64). CONCLUSION: Physician's attitudes about prenatal surgery relate to physicians' beliefs about disability as well as demographic, cultural and religious characteristics. Given the variety of views, parents are likely to receive different recommendations from their doctors about the preferable treatment choice.

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BACKGROUND: Screening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions. METHODS: One hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information. RESULTS: PCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients. CONCLUSION: While our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics.

Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.

Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected.

Identifying Needs: a Qualitative Study of women's Experiences Regarding Rapid Genetic Testing for Hereditary Breast and Ovarian Cancer in the DNA BONus Study.

Genetic testing for hereditary breast and ovarian cancer is increasingly being offered in newly diagnosed breast and ovarian cancer patients. This genetic information may influence treatment decisions. However, there are some concerns that genetic testing offered in an already vulnerable situation might be an extra burden to these women. The aim of this study was to explore the experiences of women who had been offered and accepted genetic testing when newly diagnosed with breast or ovarian cancer. Four semi-structured focus-group interviews were conducted with 17 women recruited from a Norwegian multicenter study. The material was condensed, and conventional qualitative analysis was used to identify patterns in the participants' descriptions. Three core themes were identified: 1) being "beside oneself" 2) altruism and ethical dilemmas 3) the need for support and counselling to assist the decision process. The present study indicates that women who are offered genetic testing when newly diagnosed with breast or ovarian cancer want a consultation with a health professional. Personalized support and counselling might empower women to improve their ability to manage and comprehend this overwhelming situation, and find meaning in this experience.

What can we Learn from Patients' Ethical Thinking about the right 'not to know' in Genomics? Lessons from Cancer Genetic Testing for Genetic Counselling.

This article is based on a qualitative empirical project about a distinct kinship group who were among the first identified internationally as having a genetic susceptibility to cancer (Lynch Syndrome). 50 were invited to participate (42 were tested; eight declined genetic testing). 15, who had all accepted testing, were interviewed. They form a unique case study. This study aimed to explore interviewees' experiences of genetic testing and how these influenced their family relationships. A key finding was that participants framed the decision to be tested as 'common sense'; the idea of choice around the decision was negated and replaced by a moral imperative to be tested. Those who did not follow 'common sense' were judged to be imprudent. Family members who declined testing were discussed negatively by participants. The article addresses what is ethically problematic about how test decliners were discussed and whether these ethical concerns extend to others who are offered genetic testing. Discussions showed that genetic testing was viewed as both an autonomous choice and a responsibility. Yet the apparent conflict between the right to autonomy and the moral imperative of responsibility allowed participants to defend test decliners' decisions by expressing a preference for or defending choice over responsibility. The 'right not to know' seemed an important moral construct to help ethically manage unpopular decisions made by close family who declined testing. In light of this research, the erosion of the 'right not to know' in the genomic age could have subtle yet profound consequences for family relationships.