Half of germline pathogenic and likely pathogenic variants found on panel tests do not fulfil NHS testing criteria.

Genetic testing for cancer predisposition has been curtailed by the cost of sequencing, and testing has been restricted by eligibility criteria. As the cost of sequencing decreases, the question of expanding multi-gene cancer panels to a broader population arises. We evaluated how many additional actionable genetic variants are returned by unrestricted panel testing in the private sector compared to those which would be returned by adhering to current NHS eligibility criteria. We reviewed 152 patients referred for multi-gene cancer panels in the private sector between 2014 and 2016. Genetic counselling and disclosure of all results was standard of care provided by the Consultant. Every panel conducted was compared to current eligibility criteria. A germline pathogenic / likely pathogenic variant (P/LP), in a gene relevant to the personal or family history of cancer, was detected in 15 patients (detection rate of 10%). 46.7% of those found to have the P/LP variants (7 of 15), or 4.6% of the entire set (7 of 152), did not fulfil NHS eligibility criteria. 46.7% of P/LP variants in this study would have been missed by national testing guidelines, all of which were actionable. However, patients who do not fulfil eligibility criteria have a higher Variant of Uncertain Significance (VUS) burden. We demonstrated that the current England NHS threshold for genetic testing is missing pathogenic variants which would alter management in 4.6%, nearly 1 in 20 individuals. However, the clinical service burden that would ensue is a detection of VUS of 34%.

A new scale informed by the Reciprocal-Engagement Model for quality evaluation of genetic counselling by patients: Development and initial validation.

Monitoring the quality of genetic counselling is essential to ensure appropriate provision. This study describes the development and initial psychometric validation of a novel scale for genetic counselling quality evaluation by patients. A deductive approach was taken to formulate scale items. Exploratory factor analysis with the principal axis factoring method was used to assess the scale's factor structure (n = 118). Internal consistency (Cronbach's Alpha) was also examined. Exploratory factor analysis resulted in a single overarching construct consisting of seven factors, which account for 59% of the variance explained. Items showed, in general, strong factor loadings (>0.5). Some items focused on patient satisfaction with services provision did not load onto the factors. Thus, another factor analysis was performed with these items, which resulted in one-factor. The identified factor accounted for 57% of variance explained, and communalities were strong (≥0.5) for most items. Cronbach's alpha score for the scale was 0.85, indicating high internal consistency. Factors were significantly and moderately interrelated (from r = 0.31 to r = 0.71). Further studies are needed to establish the psychometric validity of the scale.

Predictors of empowerment in parents of children with autism and related neurodevelopmental disorders who are undergoing genetic testing.

BACKGROUND: There is limited empirical data quantifying the utility of genetic testing for families of children with autism spectrum disorder (ASD) or related neurodevelopmental disorders (NDD). We assessed the utility of clinical chromosomal microarray analysis (CMA), defined by diagnostic yield and parental empowerment, in population-based sample of parents of affected children; and explored child, family, and health services factors predictive of empowerment. METHODS: Participants were families of children undergoing diagnostic assessments, between 2016 and 2019. Diagnostic yield of CMA in affected children was determined. Parental empowerment was measured through adapted version of the Genetics Counseling Outcome Scale-24. Parents completed questionnaires to capture child, family, and health service factors. RESULTS: The diagnostic yield of CMA was 2.8% for pathogenic variants. Parental empowerment was significantly correlated with family functioning and aspects of perceived family-centeredness of care. The model accounted for 49.8% of the variation in parental empowerment, F (10,37) = 3.67, p = 0.002. After accounting for other predictors, parental perception of the provision of general information remained significantly associated with empowerment. CONCLUSION: The informational needs of families play an important role in their empowerment during genetic testing. Meeting these needs and monitoring empowerment can aid genomic technologies integration in personalized healthcare for ASD/NDD.

Pretest Genetic Education Video Versus Genetic Counseling for Men Considering Prostate Cancer Germline Testing: A Patient-Choice Study to Address Urgent Practice Needs.

PURPOSE: Germline testing (GT) for prostate cancer (PCA) is now central to treatment and hereditary cancer assessment. With rising demand for and shortage of genetic counseling (GC), tools to deliver pretest informed consent across practice settings are needed to improve access to GT and precision care. Here, we report on Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER), a patient-choice study for pretest video-based genetic education (VBGE) versus GC to inform urgent practice needs. PATIENTS AND METHODS: Men with PCA or at risk for PCA (family history of PCA) were eligible and could choose pretest VBGE or GC. Outcomes included decisional conflict for GT, change in genetics knowledge, satisfaction, and intention to share results with family and/or providers. Descriptive statistics summarized results with counts and percentages for categorical variables and mean ± standard deviation for continuous variables. Data were compared with Fisher's exact, chi-squared, or Wilcoxon two-sample tests. Mean change in genetics knowledge was compared with t tests. The significance level was set a priori at .05. RESULTS: Data on the first 127 participants were analyzed. Characteristics were White (85.8%), bachelor's degree (66.9%), and PCA diagnosis (90.6%). The majority chose VBGE (71%) versus GC (29%; P < .001). No differences were observed in decisional conflict for GT or satisfaction. Cancer genetics knowledge improved in both groups without significant difference (+0.9 VBGE, +1.8 GC, P = .056). Men who chose VBGE had higher intention to share GT results (96.4% VBGE v 86.4% GC, P = .02). Both groups had high rates of GT uptake (VBGE 94.4%, GC 92%). CONCLUSION: A substantial proportion of men opted for pretest VBGE, with comparable patient-reported outcomes and uptake of GT. The results support the use of pretest video to address the critical GC shortage in the precision era.

Genetic counseling practice for inherited eye diseases in an Israeli medical center during the COVID-19 pandemic.

Inherited eye diseases (IED) are among the most common causes for childhood and young adulthood blindness in developed countries. Genetic counseling and testing have become an essential part of caregiving for families affected by one of these severe ocular pathologies. The objective of our study is to describe our experience during the 2020 (COVID-19) pandemic, following a practice protocol of safe genetic counseling for inherited ophthalmic diseases. We conducted a review of the genetic counseling practices from January until December 2020 in a multidisciplinary clinic for patients with visual impairment, in a tertiary hospital. The new protocol covered patient screening, required personal protective equipment, and the implementation of telemedicine. One hundred and eighty-three counseling sessions were done in this period of time; 33/183 were telemedicine counseling. The results of this study indicate that the practice of genetic counseling in regard to inherited eye diseases in the era of COVID-19 is effective and safe. Despite the high risk of infectivity that threatened healthcare professionals, safety measures adopted to reduce the risk of infection allowed us to prevent the cancelation of routine counseling, while keeping patient care our priority. The use of telemedicine was a very useful tool for providing counseling during lockdown periods in 2020.

Parents' experiences of decision making for rapid genomic sequencing in intensive care.

The clinical utility of rapid genomic sequencing (rGS) for critically unwell infants and children has been well demonstrated. Parental capacity for informed consent has been questioned, yet limited empirical data exists to guide clinical service delivery. In an Australian nationwide clinical implementation project offering rGS for critically unwell infants and children, parents made a decision about testing in under a day on average. This study reports parents' experiences of decision making for rGS within this rapid timeframe to inform pre-test counselling procedures for future practice. A nationwide sample of 30 parents, whose children were amongst the first to receive rGS, were interviewed. We found that framing and delivery of rGS require careful consideration to support autonomous decision making and avoid implicit coercion in a stressful intensive care setting. Many parents described feeling 'special' and 'lucky' that they were receiving access to expensive and typically time-consuming genomic sequencing. Thematic analysis revealed a spectrum of complexity for decision making about rGS. Some parents consented quickly and were resistant to pre-test counselling. Others had a range of concerns and described deliberating about their decision, which they felt rushed to make. This research identifies tensions between the medical imperative of rGS and parents' decision making, which need to be addressed as rGS becomes routine clinical care.

Recommendation of premarital genetic screening in the Syrian Jewish community based on mutation carrier frequencies within Syrian Jewish cohorts.

BACKGROUND: There is a paucity of information available regarding the carrier frequency for autosomal recessive pathogenic variants among Syrian Jews. This report provides data to support carrier screening for a group of autosomal recessive conditions among Syrian Jews based on the population frequency of 40 different pathogenic variants in a cohort of over 3800 individuals with Syrian Jewish ancestry. METHODS: High throughput PCR amplicon sequencing was used to genotype 40 disease-causing variants in 3840 and 5279 individuals of Syrian and Iranian Jewish ancestry, respectively. These data were compared with Ashkenazi Jewish carrier frequencies for the same variants, based on roughly 370,000 Ashkenazi Jewish individuals in the Dor Yeshorim database. RESULTS: Carrier screening identified pathogenic variants shared among Syrian, Iranian, and Ashkenazi Jewish groups. In addition, alleles unique to each group were identified. Importantly, 8.2% of 3401 individuals of mixed Syrian Jewish ancestry were carriers for at least one pathogenic variant. CONCLUSION: The findings of this study support the clinical usefulness of premarital genetic screening for individuals with Syrian Jewish ancestry to reduce the incidence of autosomal recessive disease among persons with Syrian Jewish heritage.

Impact of changing guidelines on genetic testing and surveillance recommendations in a contemporary cohort of breast cancer survivors with family history of pancreatic cancer.

Changing practice guidelines and recommendations have important implications for cancer survivors. This study investigated genetic testing patterns and outcomes and reported family history of pancreatic cancer (FHPC) in a large registry population of breast cancer (BC) patients. Variables including clinical and demographic characteristics, FHPC in a first or second-degree relative, and genetic testing outcomes were analyzed for BC patients diagnosed between 2010 and 2018 in the NYU Langone Health Breast Cancer Database. Among 3334 BC patients, 232 (7%) had a positive FHPC. BC patients with FHPC were 1.68 times more likely to have undergone genetic testing (p < 0.001), but 33% had testing for BRCA1/2 only and 44% had no genetic testing. Pathogenic germline variants (PGV) were identified in 15/129 (11.6%) BC patients with FHPC, and in 145/1315 (11.0%) BC patients without FHPC. Across both groups, updates in genetic testing criteria and recommendations could impact up to 80% of this cohort. Within a contemporary cohort of BC patients, 7% had a positive FHPC. The majority of these patients (56%) had no genetic testing, or incomplete testing by current standards, suggesting under-diagnosis of PC risk. This study supports recommendations for survivorship care that incorporate ongoing genetic risk assessment and counseling.

Identification of women at risk for hereditary breast and ovarian cancer in a sample of 1000 Slovenian women: a comparison of guidelines.

BACKGROUND: An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines. METHODS: Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored. RESULTS: NCCN guidelines identify 13.2% of women, ACMG/NSGC guidelines identify 7.1% of women, and SGO guidelines identify 7.0% of women from the Slovenian population, while 6.2% of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer. CONCLUSIONS: We identified 13.7% of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying nearly twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.

Health system interventions to integrate genetic testing in routine oncology services: A systematic review.

BACKGROUND: Integration of genetic testing into routine oncology care could improve access to testing. This systematic review investigated interventions and the tailored implementation strategies aimed at increasing access to genetic counselling and testing and identifying hereditary cancer in oncology. METHODS: The search strategy results were reported using the PRISMA statement and four electronic databases were searched. Eligible studies included routine genetic testing for breast and ovarian cancer or uptake after universal tumour screening for colorectal or endometrial cancer. The titles and abstracts were reviewed and the full text articles screened for eligibility. Data extraction was preformed using a designed template and study appraisal was assessed using an adapted Newcastle Ottawa Scale. Extracted data were mapped to Proctor's et al outcomes and the Consolidated Framework for Implementation Research and qualitatively synthesised. RESULTS: Twenty-seven studies, published up to May 2020, met the inclusion criteria. Twenty-five studies ranged from poor (72%), fair to good (28%) quality. Most interventions identified were complex (multiple components) such as; patient or health professional education, interdisciplinary practice and a documentation or system change. Forty-eight percent of studies with complex interventions demonstrated on average a 35% increase in access to genetic counselling and a 15% increase in testing completion. Mapping of study outcomes showed that 70% and 32% of the studies aligned with either the service and client or the implementation level outcome and 96% to the process or inner setting domains of the Consolidated Framework for Implementation Research. CONCLUSION: Existing evidence suggests that complex interventions have a potentially positive effect towards genetic counselling and testing completion rates in oncology services. Studies of sound methodological quality that explore a greater breadth of pre and post implementation outcomes and informed by theory are needed. Such research could inform future service delivery models for the integration of genetics into oncology services.

Mainstream genetic testing for breast cancer patients: early experiences from the Parkville Familial Cancer Centre.

The demand for genetic testing of hereditary breast cancer genes such as BRCA1 and BRCA2 has continued to increase with the lowering costs of testing, raised awareness in the general public, and implications for breast cancer treatment when a patient is identified as having a germline pathogenic variant. Historically within Australia, patients affected by high genetic risk breast cancers have been referred to a familial cancer centre (FCC) for assessment and testing, resulting in wait times for an appointment for pre- and post-test genetic counselling and an increased demand on the public-funded FCC. To improve patient access and pace of genetic testing, as well as refocus FCC resources, a mainstream clinical genetic testing program was rolled out in September 2017 through the Parkville FCC (PFCC) in Australia at 10 hospital sites. This program enables specialist doctors of eligible patients affected by breast cancer to arrange genetic testing directly at an oncology/surgical appointment and follow up the results as part of the patients' routine clinical care. In this model, the specialist doctor is responsible for any treatment implications of the genetic test result, and the PFCC is responsible for result interpretation, future cancer risk, family cascade testing and segregation testing where warranted. To date the program has had successful uptake, a notable pathogenic variant detection rate, reduced the burden on the PFCC enabling a reallocation of resources and has streamlined the process of genetic testing for eligible patients. Investigation into the patient and clinician experiences of the mainstream program is required.

Partners in care.

This festschrift contribution, written for my colleague and mentor John Graham, reflects on geneticist-genetic counselor interactions in clinical care, samples of alternative models of care for pediatric and general genetic counselors, and avenues for expanding access to genetic healthcare services utilizing genetic counselors.

Efectividad y aspectos éticos del asesoramiento genético en Cuba / Effectiveness and ethical aspects of genetic counseling in Cuba

Introducción: El asesoramiento genético constituye el proceso central en el manejo de trastornos de causa genética, de ahí la importancia de evaluar su efectividad. Objetivo: Evaluar la efectividad y aspectos éticos del asesoramiento genético en Cuba. Métodos: Se realizó un estudio observacional - descriptivo - retrospectivo de 2003 a 2013, que consistió en la realización de entrevistas, basadas en instrumentos diseñados y validados, a familias atendidas en los servicios de asesoramiento genético y a otros ciudadanos, la muestra quedó constituida por 13 142 individuos. Resultados: El nivel de conocimientos adquiridos fue bueno en 71,1 por ciento de los participantes; predominaron las decisiones muy racionales (68,4 por ciento); en 74,9 por ciento de las familias se logró un buen ajuste en relación con la situación particular. Existe en la población una elevada satisfacción con los servicios de asesoramiento genético (89,8 por ciento). La mayoría considera la prevención secundaria de enfermedades el objetivo más prioritario de la genética médica (81,3 por ciento), 93 por ciento está de acuerdo con el aborto selectivo como opción reproductiva ante el diagnóstico de enfermedades genéticas graves y de inicio precoz, y 76,5 por ciento prefiere el enfoque no directivo del asesoramiento genético. Conclusiones: El asesoramiento genético que se ofrece en los servicios de genética médica de Cuba es efectivo, satisface las expectativas de la población y cumple con principios éticos universalmente aceptados. La metodología diseñada y aplicada, basada en la organización de los servicios de genética en Cuba, permite la evaluación sistemática del asesoramiento genético, lo que propicia su mejoramiento y la posibilidad de trazar estrategias locales para aumentar su eficacia y alcanzar su excelencia(AU)

Introduction: Genetic counseling is the central process in the management of genetic disorders, hence the importance of assessing its effectiveness. Objective: Assess the effectiveness and ethical aspects of genetic counseling in Cuba. Methods: An observational - descriptive - retrospective study was conducted from 2003 to 2013, which consisted of conducting interviews based on instruments designed and validated with families assisted in genetic counseling services and other citizens; the sample consisted of 13 142 individuals. Results: The level of knowledge acquired was good in 71.1 percent of the participants; very rational decisions predominated (68.4 percent); in 74.9 percent of the families a good adjustment was achieved in relation to the particular situation. The population is highly satisfied with the genetic counselling services (89.8 percent). Most consider secondary diseases prevention to be the top priority for medical genetics (81.3 percent), 93 percent agree with selective abortion as a reproductive option after a diagnosis of serious and early-onset genetic diseases, and 76.5 percent prefer the non-directive approach to genetic counseling. Conclusions: The genetic counseling offered in the medical genetics services of Cuba is effective, satisfies the expectations of the population and complies with universally accepted ethical principles. The methodology designed and applied, based on the organization of genetic services in Cuba, allows the systematic assessment of genetic counseling, which males possible their improvement and the chance of devising local strategies to increase their effectiveness and achieve excellence in the service(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.

Asesoramiento genético en cáncer de próstata: ¿cómo implementarlo en la práctica clínica diaria? / Genetic counseling in prostate cancer: How to implement it in daily clinical practice?

El cáncer de próstata tiene un protagonismo socio-sanitario innegable en nuestros días y sistemas de salud. Su impacto epidemiológico cuantitativamente está muy próximo a otros tumores como el cáncer de colon y el cáncer de mama, en los que el asesoramiento genético forma parte de su práctica clínica habitual, tanto en la evaluación inicial como en la selección de estrategias terapéuticas. Los síndromes de cáncer hereditario, mama/ovario y síndrome de Lynch, forman parte del asesoramiento genético en estos tumores y hoy día también sabemos que pueden tener relación con el cáncer de próstata. Ha llegado el momento de implementar el asesoramiento genético en cáncer de próstata desde las etapas más iniciales de su abordaje, desde la sospecha inicial hasta los tumores más avanzados.Presentamos una revisión actualizada de nuestro grupo de trabajo interdisciplinar sobre la literatura científica, guías de práctica clínica y documentos de consenso hasta la creación y redacción de un «Protocolo de asesoramiento genético en cáncer de próstata», centrado en el estudio de línea germinal, de fácil aplicabilidad en los diferentes entornos asistenciales. Dicho protocolo se encuentra actualmente implementado en nuestra práctica habitual y da respuesta a tres preguntas concretas: ¿A quién realizar asesoramiento genético en cáncer de próstata?, ¿qué panel de genes analizar?, y ¿cómo aconsejar de acuerdo con los resultados obtenidos? Otros aspectos acerca de quién debe realizar el asesoramiento genético, consideraciones éticas y normativa también son recogidos

Prostate cancer plays an undeniably prominent role in public health in our days and health systems. Its epidemiological impact is quantitatively very close to that of other tumors such as colon cancer and breast cancer, in which genetic counseling is part of their routine clinical practice, both in the initial evaluation and in the selection of therapeutic strategies. Hereditary cancer syndromes, breast/ovarian and Lynch syndrome are part of genetic counseling in these tumors. Currently, we also know that they can be associated to prostate cancer. The time has come to implement genetic counseling in prostate cancer from the earliest stages of its approach, from initial suspicion to the most advanced tumors. We present an updated review carried out by our interdisciplinary working group on scientific literature, clinical practice guidelines and consensus documents, aimed at the creation and drafting of a'Protocol for genetic counseling in prostate cancer' for the study of germline, with easy application in different healthcare settings. This protocol is currently being implemented in our routine practice and provides answers to 3 specific questions: Who should receive genetic counseling for prostate cancer? Which gene panel should be analyzed? How should counseling be done according to the results obtained? Other aspects about who should perform genetic counseling, ethical considerations and regulations are also collected

Synthesis of major pharmacogenomics pretest counseling themes: a multisite comparison.

The accessibility of pharmacogenomic (PGx) testing has grown substantially over the last decade and with it has arisen a demand for patients to be counseled on the use of these tests. While guidelines exist for the use of PGx results; objective determinants for who should receive PGx testing remain incomplete. PGx clinical services have been created to meet these screening and education needs and significant variability exists between these programs. This article describes the practices of four PGx clinics during pretest counseling sessions. A description of the major tenets of the benefits, limitations and risks of testing are compiled. Additional tools are provided to serve as a foundation for those wishing to begin or expand their own counseling service.

Rapid deployment of a telemedicine care model for genetics and metabolism during COVID-19.

The national importance of telemedicine for safe and effective patient care has been highlighted by the current COVID-19 pandemic. Prior to the 2020 pandemic the Division of Genetics and Metabolism piloted a telemedicine program focused on initial and follow-up visits in the patients' home. The goals were to increase access to care, decrease missed work, improve scheduling, and avoid the transport and exposure of medically fragile patients. Visits were conducted by physician medical geneticists, genetic counselors, and biochemical dietitians, together and separately. This allowed the program to develop detailed standard operating procedures. At the onset of the COVID-19 pandemic, this pilot-program was deployed by the full team of 22 providers in one business day. Two physicians remained on-site for patients requiring in-person evaluations. This model optimized patient safety and workforce preservation while providing full access to patients during a pandemic. We provide initial data on visit numbers, types of diagnoses, and no-show rates. Experience in this implementation before and during the pandemic has confirmed the effectiveness and value of telemedicine for a highly complex medical population. This program is a model that can and will be continued well-beyond the current crisis.

A report on the impact of rapid prenatal exome sequencing on the clinical management of 52 ongoing pregnancies: a retrospective review.

OBJECTIVE: Studies have shown that prenatal exome sequencing (PES) improves diagnostic yield in cases of fetal structural malformation. We have retrospectively analysed PES cases from two of the largest fetal medicine centres in the UK to determine the impact of results on management of a pregnancy. DESIGN: A retrospective review of clinical case notes. SETTING: Two tertiary fetal medicine centres. POPULATION: Pregnancies with fetal structural abnormalities referred to clinical genetics via a multidisciplinary team. METHODS: We retrospectively reviewed the notes of all patients who had undergone PES. DNA samples were obtained via chorionic villus sampling or amniocentesis. Variants were filtered using patient-specific panels and interpreted using American College of Medical Genetics guidelines. RESULTS: A molecular diagnosis was made in 42% (18/43) ongoing pregnancies; of this group, there was a significant management implication in 44% (8/18). A positive result contributed to the decision to terminate a pregnancy in 16% (7/43) of cases. A negative result had a significant impact on management in two cases by affirming the decision to continue pregnancy. CONCLUSIONS: We demonstrate that the results of PES can inform pregnancy management. Challenges include variant interpretation with limited phenotype information. These results emphasise the importance of the MDT and collecting phenotype and variant data. As this testing is soon to be widely available, we should look to move beyond diagnostic yield as a measure of the value of PES. TWEETABLE ABSTRACT: Prenatal exome sequencing can aid decision-making in pregnancy management; review ahead of routine implementation in NHS.

Mainstream consent programs for genetic counseling in cancer patients: A systematic review.

As demand for germline genetic testing for cancer patients increases, novel methods of genetic counseling are required. One such method is the mainstream consent pathway, whereby a member of the oncology team (rather than a genetic specialist) is responsible for counseling, consenting, and arranging genetic testing for cancer patients. We systematically reviewed the literature for evidence evaluating mainstream pathways for patients with breast, ovarian, colorectal, and prostate cancer. Medline, EMBASE, and Cochrane Library were searched for studies that met inclusion and exclusion criteria. Article references were checked for additional studies. Trial databases were searched for ongoing studies. Of the 13 papers that met inclusion criteria, 11 individual study groups were identified (two study groups had two publications each). Ten of the 11 studies evaluated the acceptability, feasibility, and impact of BRCA testing for patients and/or clinicians in different clinical settings in breast and ovarian cancer, while the final study explored the attitudes of colorectal specialists toward genetic testing for colorectal cancer. None involved prostate cancer. Overall, mainstream pathways were acceptable and feasible. Medical oncologist- and nurse-driven pathways were particularly successful, with both patients and clinicians satisfied with this process. Although the content of pretest counseling was less consistent compared with counseling via the traditional model, patients were largely satisfied with the education they received. Further research is required to evaluate the mainstream pathway for men with prostate cancer.

DNA damage repair gene mutation testing and genetic counseling in men with/without prostate cancer: a systematic review.

Background: Ongoing clinical trials are investigating PARP inhibitors to target the DNA damage repair (DDR) pathway in prostate cancer. DDR mutation screening will guide treatment strategy and assess eligibility for clinical trials. Materials & methods: This systematic review estimated the rate of DDR mutation testing or genetic counseling among men with or at risk of prostate cancer. Results: From 6856 records, one study fulfilled the inclusion criteria and described men undiagnosed with prostate cancer with a family history of BRCA1/2 mutation who received DDR mutation testing. Conclusion: With only one study included in this first systematic review of DDR mutation testing or genetic counseling in men with or at risk of prostate cancer, more research is warranted.