Post-test Genetic Counseling Research Articles

Genetic Counseling in the Era of Genomics: What's all the Fuss about?

As genomic sequencing becomes more widely available in clinical settings for diagnostic purposes, a number of genetic counseling issues are gaining precedence. The ability to manage these issues will be paramount as genetic and non-genetic healthcare professionals navigate the complexities of using genomic technologies to facilitate diagnosis and inform patient management. Counseling issues arising when counseling for diagnostic genomic sequencing were identified by four genetic counselors with 10yearsof collective experience providing genetic counseling in this setting. These issues were discussed and refined at a meeting of genetic counselors working in clinical genomics settings in Melbourne, Australia. Emerging counseling issues, or variations of established counseling issues, were identified from the issues raised. Illustrative cases were selected where pre- and post-test genetic counseling was provided in clinical settings to individuals who received singleton or trio WES with targeted analysis. Counseling issues discussed in this paper include a reappraisal of how genetic counselors manage hope in the genomic era, informed consent for secondary use of genomic data, clinical reanalysis of genomic data, unexpected or unsolicited secondary findings, and trio sequencing. The authors seek to contribute to the evolving understanding of genetic counseling for diagnostic genomic sequencing through considering the applicability of existing genetic counseling competencies to managing emerging counseling issues and discussing genetic counseling practice implications.

Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening

BackgroundCurrent professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance.ResultsWe identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity.ConclusionOur analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.

Next generation sequencing to promote the diagnosis and treatment of rare genetic diseases

Next generation sequencing (NGS) based test provided us an unprecedented power for the molecular diagnosis of rare diseases with genetic etiology, thus enabling the practice of precision medicine. In order to maximize the clinical utilities of NGS-based test, attention should be paid to the improvement of the sequencing technology, data quality and the accuracy of data interpretation, as well as the clinical correlations and pre- and post-test genetic counseling services. In doing so, it is believed practice of NGS-based test can bring expected benefit to many patients and families.(Chin J Lab Med, 2017, 40: 486-488) Key words: Genetic Diseases, inborn; High-throughput nucleotide sequencing; Genetic counseling

Abstract DPOC-004: MAGENTA: MAking GENetic Testing more Accessible

Abstract The standard paradigm for cancer susceptibility genetic testing has been for patients to 1) be identified by their provider as being at high risk due to extensive family history or another diagnosis (e.g., breast cancer for ovarian risk testing), and 2) attend in–person pre and post– genetic test sessions with a genetic counselor to prepare for testing and learn about the results. This arrangement places boundaries around the types of women willing to spend this time and effort receiving testing, as providers are required to act as gatekeepers to the testing process. More open methods of accessing genetic testing and providing support need to be evaluated. We propose to deliver personal, risk–based genetic testing and results to women from the general public using the Internet. Internet–based services offer several advantages over either in–person or telephone interventions. First, information can be accessed by participants and providers on their own schedules, at any location with internet access, and can be consumed at the pace and style that is best for individual tastes and styles. If necessary, information and support can be re–reviewed if the patient does not remember the initial counseling session. Second, delivery of information through the internet can be performed in a more efficient and cost–effective manner, reserving the limited in–person genetic counseling for individuals who need it the most, while providing support to the general public about basic medical and risk–based information. Recruitment via social media outlets can directly link potential participants to the Internet systems that screen for eligibility and provide testing support. Finally, Internet delivery can bring genetic testing to the patient in their home, eliminating a major barrier to testing (multiple visits to the provider) The main objective of MAGENTA is to test the effects of on–line genetic education versus telephone genetic counseling on cancer distress and other psychological outcomes. We will recruit women using social media and other eHealth methods to participate in a randomized trial of ovarian cancer counseling and testing that is conducted online and using the telephone. We will conduct a (2x2 factorial design) randomized trial to test online versus telephone pre– and post–test genetic counseling for ovarian cancer risk among women at higher than average risk for ovarian cancer. We expect to enroll 3000 women through our media contacts to participate in MAGENTA. For genetic risk assessment, we will evaluate and provide feedback on 19 breast and ovarian cancer (OC) genes that have a clear relationship to cancer risk in collaboration with Color Genomics. Variants include ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MSH2, MSH6, MLH1, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, TP53, and STK1. We will follow women for main psychological outcomes at 3 months post testing and longer for other outcomes. Citation Format: Swisher E., Lu K., Bowen DJ, Gavin K. MAGENTA: MAking GENetic Testing more Accessible [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr DPOC-004.

Insights from early experience of a Rare Disease Genomic Medicine Multidisciplinary Team: a qualitative study

Whole-exome/whole-genome sequencing (WES/WGS) has the potential to enhance genetic diagnosis of rare disease, and is increasingly becoming part of routine clinical care in mainstream medicine. Effective translation will require ongoing efforts in a number of areas including: selection of appropriate patients, provision of effective consent, pre- and post-test genetic counselling, improving variant interpretation algorithms and practices, and management of secondary findings including those found incidentally and those actively sought. Allied to this is the need for an effective education programme for all members of clinical teams involved in care of patients with rare disease, as well as to maintain public confidence in the use of these technologies. We established a Genomic Medicine Multidisciplinary Team (GM-MDT) in 2014 to build on the experiences of earlier successful research-based WES/WGS studies, to address these needs and to review results including pertinent and secondary findings. Here we report on a qualitative study of decision-making in the GM-MDT combined with analysis of semi-structured interviews with GM-MDT members. Study findings show that members appreciate the clinical and scientific diversity of the GM-MDT and value it for education and oversight. To date, discussions have focussed on case selection including the extent and interpretation of clinical and family history information required to establish likely monogenic aetiology and inheritance model. Achieving a balance between effective use of WES/WGS – prioritising cases in a diverse and highly complex patient population where WES/WGS will be tractable – and meeting the recruitment targets of a large project is considered challenging.

Attitudes towards non-invasive prenatal diagnosis among obstetricians in Pakistan, a developing, Islamic country.

Stakeholders' views are essential for informing implementation strategies for non-invasive prenatal testing (NIPT). Little is known about such views in developing countries. We explored attitudes towards NIPT among obstetricians in Pakistan, a developing, Islamic country. A 35-item questionnaire was distributed and collected at eight events (a national conference and seven workshops in five cities) for obstetric professionals on advances in fetal medicine. Responses from 113 obstetrician show positive attitudes towards implementation of NIPT: 95% agreed prevention of genetic conditions was a necessity, and 97% agreed public hospitals should provide prenatal screening tests. However, participants also agreed the availability of NIPT would increase social pressure on women to have prenatal screening tests and to terminate an affected pregnancy (53% and 63%, respectively). Most participants would not offer NIPT for sex determination (55%), although 31% would. The most valued aspects of NIPT were its safety, followed by its utility and then accuracy. Participants generally supported the implementation of NIPT but raised concerns about social implications. Therefore, national policy is needed to regulate the implementation of NIPT, and pretest information and post-test genetic counselling are needed to mitigate social pressure and support parents to make informed decisions. © 2017 John Wiley & Sons, Ltd.

Mainstreaming cancer genetics: A model integrating germline BRCA testing into routine ovarian cancer clinics

ObjectiveOwing to the rapid increase in clinical need, we aimed to implement and review the performance of a mainstreaming model of germline BRCA1/2 genetic testing in eligible women with high grade non-mucinous epithelial ovarian cancer via a Genetic Counselor embedded in the gynecology oncology clinic. MethodsThe model implemented involved a specialized referral form, weekly genetics-lead multidisciplinary review of referrals, and pre- and post-test genetic counseling provided by an embedded genetic counselor during chemotherapy chair time. Performance and outcomes were retrospectively audited over the following two consecutive one year periods, including survey data on medical specialist comfort with mainstreaming and the model. ResultsSixty-four women underwent mainstreamed BRCA1/2 testing over the two year post-implementation period with a rate of detection of BRCA1/2 pathogenic variants of 17%. The referral rate for eligible women significantly increased to over 90% (p<0.001). The median time from referral to delivery of genetic testing results was less than five months, with >90% of patients receiving results during first line chemotherapy. Genetic counseling time decreased from 120 to 54min. Cancer specialists were comfortable with the model. ConclusionsThe mainstreaming model proved effective, increasing uptake of genetic testing in eligible patients to over 90%; it was efficient for patients, genetic counselors and cancer specialists and acceptable to cancer specialists. It facilitated co-location of genetic and oncology service delivery but separation of clinical responsibility for genetic testing to a specialist genetics service, ensuring accurate and robust patient-centred care.

Counselling considerations for chromosomal mosaicism detected by preimplantation genetic screening

The evolution of preimplantation genetic screening (PGS) for aneuploidy to blastocyst biopsy and more sensitive 24-chromosome screening techniques has resulted in a new diagnostic category of PGS results: those classified as mosaic. This diagnosis presents significant challenges for clinicians in developing policies regarding transfer and storage of such embryos, as well as in providing genetic counselling for patients prior to and following PGS. Given the high frequency of mosaic PGS results and the wide range of possible associated outcomes, there is an urgent need to understand how to appropriately counsel patients regarding such embryos. This is the first commentary to thoroughly address pre- and post-test genetic counselling recommendations, as well as considerations regarding prenatal screening and diagnosis. Current data on mosaic PGS results are summarized along with embryo selection considerations and potential outcomes of embryos diagnosed as mosaic.

Prenatal diagnosis of susceptibility loci for neurodevelopmental disorders - genetic counseling and pregnancy outcome in 57 cases.

Whole genome array testing not only provides an increased diagnostic yield of pathogenic causative findings, but it may also reveal so called susceptibility loci (SL) for neurodevelopmental disorders. The goal of this study was to evaluate the pregnancy outcomes in SL cases and to establish a protocol for pregnancy management, follow-up and additional investigations. Fifty seven cases were evaluated: 34 with and 23 without ultrasound anomalies at referral. Each pregnant couple received pretest counseling and extensive posttest genetic counseling. After diagnosis of SL, parental testing and an additional ultrasound examination were offered. The severity of the ultrasound anomalies and not the diagnosis of SL was the most important factor contributing to the decision on pregnancy continuation. In the majority of cases with milder or no ultrasound anomalies, the pregnancy was continued and a normal outcome after birth was observed. The diagnosis of a SL did not seem to be a reason for termination of pregnancy. Most patients were able to cope with the uncertainty and were interested in both prenatal and postnatal actionability of SL. Long-term follow-up is crucial to assess the actual risks for neurodevelopmental disorders, especially in families with unremarkable history. © 2016 John Wiley & Sons, Ltd.

Integration of Clinical Genetic Testing in Cardiovascular Care

Knowledge of genetic etiologies for inherited cardiovascular disease has expanded in recent years giving providers the potential to tailor medical management and family screening based on a patient’s genotype for some conditions. This paper highlights recent advances in Mendelian inherited cardiovascular disease such as Marfan syndrome, hypertrophic cardiomyopathy, and familial hypercholesterolemia. Genetic testing has gone through a rapid evolution thanks to technological advancements in sequencing technology. The combination of increased utility and decreased cost is lowering the barriers for testing. Development of next-generation panels and whole-exome and whole-genome sequencing allows for broader testing and, in some cases, gene discoveries. Genetics is fueling growth in pharmacogenetics and complex disease research and has even led to novel therapeutics and new indications for old therapeutics. The integration of clinical genetic testing into patient care is becoming increasingly common as the field expands and more institutions adopt the practice. The interpretation of genetic testing results can be complicated as there are a wide range of tools to determine the pathogenicity of a DNA variant identified in a patient. The psychological impact of genetic counseling necessitates pre- and post-test genetic counseling.

The Psychological Impact of Prenatal Diagnosis and Disclosure of Susceptibility Loci: First Impressions of Parents' Experiences.

Genomic microarray may detect susceptibility loci (SL) for neurodevelopmental disorders such as autism and epilepsy, with a yet unquantifiable risk for the fetus. The prenatal disclosure of susceptibility loci is a topic of much debate. Many health care professionals fear that reporting susceptibility loci may put a psychological burden on pregnant couples. It is our policy to disclose prenatal susceptibility loci as we recognize them as actionable for prospective parents. The aim of this report was to evaluate the psychological impact of disclosing a prenatal diagnosis of susceptibility loci. The psychological impact of disclosing susceptibility loci was evaluated in the first patients who received such results. Eight out of 15 women who had a susceptibility locus disclosed and four of their partners consented to share their experiences through a telephonic evaluation (n = 12). Follow-up time ranged from 3 to 15 months after their prenatal test result. The reporting of susceptibility loci was initially ‘shocking’ for five parents while the other seven felt ‘worried’. Ten out of 12 participants indicated they would like to be informed about the susceptibility locus again, two were unsure. Most had no enduring worries. Participants unanimously indicated that pregnant couples should have an individualized pre-test choice about susceptibility loci (non)disclosure. We observed no negative psychological impact with the prenatal diagnosis and disclosure of SL on participants. A key factor in mitigating parental anxiety with SL disclosure appears to be post-test genetic counseling. Our report confirms that pregnant women and their partners prefer an individualized choice regarding the scope of prenatal testing.

Patient-reported outcomes in a multicenter randomized study of in-person versus telephone disclosure of genetic test results for cancer susceptibility.

1502Background: Genetic testing for cancer predisposition traditionally includes in-person pre- and post-test genetic counseling. Outcomes of telephone delivery of a range of cancer genetic test re...

Abstract P2-09-06: Multi-gene panel testing for hereditary cancer risk

Abstract Background: Multi-gene panels are widely available for assessing hereditary cancer risk in high risk individuals. Due to the use of these panels, many genetic mutations other than BRCA 1 or 2 can be detected which can potentially affect management. This study presents the results of multi-gene panel testing performed at Beaumont Health System. Methods:All patients who underwent multi-gene panel testing at Beaumont Health System between November 1, 2012 and January 15, 2015 were included in this study. This cohort consisted of patients who met criteria for genetic testing due to personal or family history. All patients received comprehensive pre and post-test genetic counseling. The panels ranged from 5 to 43 genes associated with risk for breast and other cancers. Results: 653 multi-gene panel tests were performed. The majority of these consisted of either a 5 gene high risk breast panel (25%), an 18 gene moderate to high risk breast panel (21%), or a 9 gene high risk breast and gynecologic panel (17%). 184 variants of undetermined significance (VUS) were identified with a pooled VUS rate of 28%. Among the commonly used panels, there was a positive correlation between VUS rate and the number of genes included in the panel (r = 0.86, p = 0.01, Range 6% to 70%). A pathogenic mutation was identified in one or more genes in 65 (10%) panels for a total of 67 mutations. Of these, 17 mutations were in BRCA1 or BRCA2 gene. Fifty non-BRCA deleterious mutations were identified with the following frequencies: CHEK2(12), MUTYH(7 monoallelic, 1 biallelic), TP53(4), PTEN(4), ATM(4), MSH6(3), PALB2(3), MSH2(2), CDH1(2), APC(2), NF1(2), BARD1(2), MLH1(1) and PMS2(1). Of these non-BRCA mutations, 41(82%) had a significant impact on management. Conclusions: Our study demonstrates that multi-gene panel testing identifies several genes that can impact management and would likely not have been discovered by pedigree analysis alone. However, this added detection is associated with a higher VUS rate, especially using larger panels. Further research is needed to better define the role of multi-gene panel testing in high risk patients, with a focus on choosing appropriate genes, understanding the magnitude of cancer risk and delineating impact on management. Citation Format: Yadav S, Ladkany R, Fulbright J, Dreyfuss H, Reeves A, Campian S, Thomas V, Zakalik D. Multi-gene panel testing for hereditary cancer risk. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-06.

Utilizing Remote Real-Time Videoconferencing to Expand Access to Cancer Genetic Services in Community Practices: A Multicenter Feasibility Study.

BackgroundVideoconferencing has been used to expand medical services to low-access populations and could increase access to genetic services at community sites where in-person visits with genetic providers are not available.ObjectiveTo evaluate the feasibility of, patient feedback of, and cognitive and affective responses to remote two-way videoconferencing (RVC) telegenetic services at multiple sociodemographically diverse community practices without access to genetic providers.MethodsPatients at 3 community sites in 2 US states outside the host center completed RVC pretest (visit 1, V1) and post-test (visit 2, V2) genetic counseling for cancer susceptibility. Surveys evaluated patient experiences, knowledge, satisfaction with telegenetic and cancer genetics services, anxiety, depression, and cancer worry.ResultsA total of 82 out of 100 (82.0%) approached patients consented to RVC services. A total of 61 out of 82 patients (74%) completed pretest counseling and 41 out of 61 (67%) proceeded with testing and post-test counseling. A total of 4 out of 41 (10%) mutation carriers were identified: BRCA2, MSH2, and PMS2. Patients reported many advantages (eg, lower travel burden and convenience) and few disadvantages to RVC telegenetic services. Most patients reported feeling comfortable with the video camera—post-V1: 52/57 (91%); post-V2: 39/41 (95%)—and that their privacy was respected—post-V1: 56/57 (98%); post-V2: 40/41 (98%); however, some reported concerns that RVC might increase the risk of a confidentiality breach of their health information—post-V1: 14/57 (25%); post-V2: 12/41 (29%). While the majority of patients reported having no trouble seeing or hearing the genetic counselor—post-V1: 47/57 (82%); post-V2: 39/41 (95%)—51 out of 98 (52%) patients reported technical difficulties. Nonetheless, all patients reported being satisfied with genetic services. Compared to baseline, knowledge increased significantly after pretest counseling (+1.11 mean score, P=.005); satisfaction with telegenetic (+1.74 mean score, P=.02) and genetic services (+2.22 mean score, P=.001) increased after post-test counseling. General anxiety and depression decreased after pretest (-0.97 mean anxiety score, P=.003; -0.37 mean depression score, P=.046) and post-test counseling (-1.13 mean anxiety score, P=.003; -0.75 mean depression score, P=.01); state anxiety and cancer-specific worry did not significantly increase.ConclusionsRemote videoconferencing telegenetic services are feasible, identify genetic carriers in community practices, and are associated with high patient satisfaction and favorable cognitive and affective outcomes, suggesting an innovative delivery model for further study to improve access to genetic providers and services. Potential barriers to dissemination include technology costs, unclear billing and reimbursement, and state requirements for provider licensure.

Understanding the patient experience: comparing carriers and non-carriers as identified by an expanded screening panel

BACKGROUND: Expanded carrier screening (ECS) is routinely offered to patients seeking fertility treatment. ECS provides an abundance of information for patients, which may inform reproductive decisions. However this volume of information may be perceived as causing anxiety, particularly for individuals identified as carriers. OBJECTIVE: Our aim was to assess the effect of ECS results on patients identified as carriers compared to non-carriers. MATERIALS & METHODS: Patients who underwent ECS were sent a survey 3 weeks after results were reported. Post-test genetic counseling (GC) was offered to all patients. Consenting participants were asked to report 1) with whom they discussed their results and 2) how often they felt a number of emotions post-test. Responses were compared between carriers and noncarriers. RESULTS: 420 patients completed the survey and were eligible for analysis. 178 were identified as carriers (42%). Post-test GC was received by 158 (89%) of carriers. When asked to report with whom they discussed results, carriers were significantly more likely to have discussed results with family members (p 1⁄4 0.0003). Among both carriers and non-carriers, most participants reported not discussing their results with a primary care provider/other medical professional. When reporting on emotions felt post-test, carriers felt anxious, nervous, and a loss of control significantly more often than non-carriers (p1⁄45.689e-05; Fisher p1⁄4 0.0005). While the difference here was significant, the overall frequency of feeling said emotions was low; the large majority of both carriers and non-carriers felt this way rarely/never. CONCLUSIONS: It is expected that carriers may feel anxiety regarding their results. However, even among carriers, the majority reported feeling these emotions rarely/never. This may be due to post-test GC. The benefit of ECS pairedwith GC extended to participants’ families, as carriers reported discussing results with their family members. Participants reported not discussing their results with other medical professionals. The clinical impact of this is important; despite discussing their results with a genetics professional, carriers may feel anxiety regarding how their carrier status affects other areas of their health. These emotions could be mitigated by the sharing of results with other healthcare providers. Future studies around facilitation of such discussions and the impact of post-test genetic counseling will be important, as will implementation of pre-test counseling for patients undergoing screening. FINANCIAL SUPPORT: Kumar, Yarnall, and Lee are employees of Recombine.

Cytogenomic Evaluation of Children with Congenital Anomalies: Critical Implications for Diagnostic Testing and Genetic Counseling.

Identification of submicroscopic chromosomal aberrations, as a cause of structural malformations, is currently performed by MLPA (multiplex ligation-dependent probe amplification) or array CGH (array comparative genomic hybridization) techniques. The aim of this study was the evaluation of diagnostic usefulness of MLPA and array CGH in patients with congenital malformations or abnormalities (at least one major or minor birth defect, including dysmorphism) with or without intellectual disability or developmental delay and the optimization of genetic counseling in the context of the results obtained. The MLPA and array CGH were performed in 91 patients diagnosed with developmental disorders and major or minor congenital anomalies. A total of 49 MLPA tests toward common microdeletion syndromes, 42 MLPA tests for subtelomeric regions of chromosomes, two tests for common aberrations in autism, and five array CGH tests were performed. Eight (9 %) patients were diagnosed with microdeletion MLPA, four (4 %) patients with subtelomeric MLPA, one (1 %) patient with autism MLPA. Further three (3 %) individuals had rearrangements diagnosed by array CGH. Altogether, chromosomal microaberrations were found in 16 patients (17 %). All the MLPA-detected rearrangements were found to be pathogenic, but none detected with array CGH could unequivocally be interpreted as pathogenic. In patients with congenital anomalies, the application of MLPA and array CGH techniques is efficient in detecting syndromic and unique microrearrangements. Consistent pre-MLPA test phenotyping leads to better post-test genetic counseling. Incomplete penetrance and unknown inheritance of detected variants are major issues in clinical interpretation of array CGH data.

Abstract P1-11-02: Telemedicine: Expanding access to cancer genetic services to underserved populations

Abstract Background: Given the increasing demand for genetic services and limited genetic workforce, many patients do not receive recommended pre- and post-test genetic counseling. Telemedicine has been used to expand specialized medical services to low access populations. The feasibility and outcomes of telemedicine in clinical genetics are not well described. Methods: Patients at 3 community sites without genetic counseling services received real-time pre-test (V1) and post-test (V2) counseling for cancer susceptibility with a genetic counselor (GC) at a center of expertise via community sites’ and host institution’s computers equipped with web cameras and videoconferencing software. Mixed-methods surveys assessed patient knowledge, satisfaction, psychosocial responses and experiences at baseline (BL), post-V1 and post-V2. We used paired T-tests to assess change between time points and linear regressions. Results: Of 100 patients approached, 83% consented to telegenetic services. To date, 57 have completed BL and V1, and 70% proceeded with genetic testing, 31 patients have received results, including 3 carriers (BRCA2, MSH2, PMS2). Patient characteristics did not differ between those who agreed to and declined telegenetics. 4% of sessions were aborted due to technology failures. 30% experienced disconnections but were completed. Nearly all (94%) were satisfied with their telegenetic experience. Knowledge and satisfaction with telegenetic services significantly increased and general anxiety and depression significantly decreased. Event related (state) anxiety did not change significantly. Table 1.OutcomeBL Mean (sd)Post-V1 Mean(sd)Post-V2 Mean(sd)pKnowledge (6-28)20.9(2.8)22.0 (3.0) 0.007 20.8 (3.3)21.8(3.2)21.5(3.1)NSSGeneral Anxiety (0-21)7.4(4.1)6.6(4.1) 0,02 6.6 ((4.0)5.7 (3.8)5.7 (3.5)0.06Genarla Depression(0-21)3.9 (3.9)3.5 (3.4) 0,05 3.6 (3.7)3.4(3.5)2.9 (3.5)0.07State Anxiety(20-80)36.0(15.2)35.7(13.7) NSS 34.6(15.0)34.5(13.1)32.1(12.5)NSSSatisfaction with Genetic Services 39.5(3.( 39.8(4.0)42.2(3.6)0.002Satisfaction with Telemedicine 51.3(5.6) 51.5(5.7)53.0(5.3)0.008 Patients reported several advantages to telegenetics (e.g. decreased travel burden) and few disadvantages (e.g. audio challenges and technical glitches).Conclusions: Telemedicine delivery of cancer genetic services is feasible, identifies genetic mutation carriers, increases knowledge, decreases anxiety and depression and is associated with high satisfaction, suggesting an innovative model for delivery of genetic services for patients and community practices without access to local genetic providers. Citation Format: Linda Patrick-Miller, Diana Harris, Evelyn Stevens, Brian Egleston, Linda Fleisher, Rebbeca Mueller, Amanda Brandt, Jill Stopfer, Susan Domchek, Angela Bradbury. Telemedicine: Expanding access to cancer genetic services to underserved populations [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-11-02.

ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.

This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.

Creation of a National, At-home Model for Ashkenazi Jewish Carrier Screening.

Ethnicity-based carrier screening for the Ashkenazi Jewish population has been available and encouraged by advocacy and community groups since the early 1970's. Both the American College of Medical Genetics and the American Congress of Obstetricians and Gynecologists recommend carrier screening for this population (Obstetrics and Gynecology, 114(4), 950-953, 2009; Genetics in Medicine, 10(1), 55-56, 2008). While many physicians inquire about ethnic background and offer appropriate carrier screening, studies show that a gap remains in implementing recommendations (Genetic testing and molecular biomarkers, 2011). In addition, education and outreach efforts targeting Jewish communities have had limited success in reaching this at-risk population. Despite efforts by the medical and Jewish communities, many Jews of reproductive age are not aware of screening, and remain at risk for having children with preventable diseases. Reaching this population, preferably pre-conception, and facilitating access to screening is critically important. To address this need, genetic counselors at Emory University developed JScreen, a national Jewish genetic disease screening program. The program includes a national marketing and PR campaign, online education, at-home saliva-based screening, post-test genetic counseling via telephone or secure video conferencing, and referrals for face-to-face genetic counseling as needed. Our goals are to create a successful education and screening program for this population and to develop a model that could potentially be used for other at-risk populations.

Multiplex ligation-dependent probe amplification and array comparative genomic hybridization analyses for prenatal diagnosis of cytogenomic abnormalities.

BackgroundThe aims of this study were to evaluate the clinical utility of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH) analyses on prenatal cases and to review prenatal ultrasound findings of cytogenomic syndromes.ResultsOf the 54 prenatal cases analyzed, cytogenomic abnormalities were characterized in 14 cases. In four fetuses with abnormal ultrasound findings, a 40.701 Mb duplication of 8q22.3-q24.3 and a 23.839 Mb deletion of 7q33-q36.3 derived from a paternal balanced translocation, a de novo 13.062 Mb deletion of 11q24.1-q25 for Jacobsen syndrome, a de novo 19.971 Mb deletion of 7q11.23-q21.3 for type 1 split-hand/foot malformation (SHFM1), and a de novo 28.909 Mb duplication of 3q21.1-q25.1 were detected. A 699.8 Kb deletion at 5p15.33 for Cri du Chat syndrome was confirmed in a fetus with abnormal MLPA result. A fetus with abnormal maternal screening was detected with a de novo distal 1.747 Mb duplication at 2q37.1-q37.2 and a 6.664 Mb deletion at 2q37.2-q37.3. Of the eight cases referred by history of spontaneous abortions, derivative chromosomes 11 from paternal carriers of a balanced 8q/11q and a 10q/11q translocation were noted in two cases, simple aneuploids of trisomy 2 and trisomy 21 were seen in three cases, and compound aneuploids of two or three chromosomes were found in three cases. Post-test genetic counseling was performed with detailed genomic information and well characterized postnatal syndromic features.ConclusionsThese results demonstrated that coupling MLPA screening and aCGH analysis are a cost-effective approach to detect cytogenomic abnormalities in a prenatal setting. The aCGH analysis provided not only genomic maps of breakpoints and gene content of imbalanced regions but also better inference of related phenotypes for genetic counseling. Prenatal ultrasound findings reported in the literature for Jacobsen syndrome, SHFM and Cri du Chat syndrome were summarized for use as diagnostic references.