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Autosomal dominant hereditary paraganglioma-pheochromocytoma syndrome (HPPS) is a rare genetic disorder characterized by neuroendocrine tumor development associated with pathogenic variants in succinate dehydrogenase (SDH) enzyme complex genes. Particularly, HPPS linked to SDHB mutation poses a significant clinical challenge due to its association with aggressive tumor features and a high risk of malignancy. Our report underscores the diversity in the presentation of patients with SDHB-mutated paraganglioma and the feasibility of managing it with a minimally invasive surgical approach. In the first case, a 17-year-old female was diagnosed with a metabolically active, poorly differentiated extra-adrenal retroperitoneal paraganglioma that required challenging robotic resection. Cascade genetic testing revealed an SDHB mutation not only in her but also in three family members, pointing to the inherited nature of the syndrome. Conversely, the second case involves a 37-year-old male with an asymptomatic well-differentiated left paraaortic paraganglioma incidentally found during an unrelated medical examination. Robotic converted-to-open resection allowed the successful removal of the mass. Subsequent germline testing confirmed a deleterious SDHB mutation, initiating a process of familial cascade testing. Both patients remained symptom- and recurrence-free at 12 and six months, respectively. Through these cases, and supported by a literature review, we highlight the variable clinical presentations of HPPS, arising from the same genetic alteration. The successful application of minimally invasive surgical techniques, combined with genetic evaluation, emphasizes the necessity for a comprehensive, tailored approach to treatment and surveillance. This strategy not only addresses the immediate clinical needs but also fosters proactive management of at-risk family members, ensuring a multidisciplinary approach to this complex hereditary condition.
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Cascade genetic testing and surveillance reduce morbidity and mortality in Lynch syndrome. However, barriers to conveying information about genetic disorders within families result in low uptake of genetic testing. Provider-mediated interventions may increase uptake but raise legal and ethical concerns. We describe 30 years of national experience with cascade genetic testing combining family- and provider-mediated contact in Lynch syndrome families in the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Register. We aimed to estimate the added value of information letters to family members in Lynch syndrome families (provider-mediated contact) compared to family members not receiving such letters and thus relying on family-mediated contact. National clinical practice for cascade genetic testing, encompassing infrastructure, legislation, acceptance, and management of the information letters, is also discussed. Cascade genetic testing resulted in 7.3 additional tests per family. Uptake of genetic testing was 54.4% after family-mediated and 64.9% after provider-mediated contact, corresponding to an odds ratio of 1.8 (p < 0.001). The uptake of genetic testing was highest in the first year after diagnosis of Lynch syndrome in the family, with 72.5% tested after provider-mediated contact. In conclusion, the Danish model combining family- and provider-mediated contact can increase the effect of cascade genetic testing.
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Germline genetic sequencing is now at the forefront of cancer treatment and preventative medicine. Cascade genetic testing, or the testing of at-risk relatives, is extremely promising as it offers genetic testing and potentially life-saving risk-reduction strategies to a population exponentially enriched for the risk of carrying a cancer-associated pathogenic variant. However, many relatives do not complete cascade testing due to barriers that span individual, relationship, healthcare community, and societal/policy domains. We have reviewed the published research on cascade testing. Our aim is to evaluate barriers to cascade genetic testing for hereditary cancer syndromes and explore strategies to mitigate these barriers, with the goal of promoting increased uptake of cascade genetic testing.
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Predisposición Genética a la Enfermedad , Pruebas Genéticas , Síndromes Neoplásicos Hereditarios , Humanos , Pruebas Genéticas/métodos , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/diagnóstico , Mutación de Línea Germinal , Asesoramiento GenéticoRESUMEN
BACKGROUND & AIMS: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes. METHODS: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3 months postintervention. RESULTS: A total of 424 families were randomized, including 601 participants (n = 296 Arm 1; n = 305 Arm 2), 90% of whom completed genetic testing (Arm 1 [87%]; Arm 2 [93%], P = .014). Arm 1 participants were significantly less likely to complete genetic testing compared with Arm 2 participants (adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). Among participants who completed patient-reported psychological outcomes questionnaires (Arm 1 [n = 194]; Arm 2 [n = 206]), the intervention did not affect mean anxiety, depression, or cancer worry scores. CONCLUSIONS: Remote genetic education and testing can be a successful and complementary option for delivering genetics care. (Clinicaltrials.gov, number NCT03762590).
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Carcinoma Ductal Pancreático , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Neoplasias Pancreáticas , Medición de Resultados Informados por el Paciente , Telemedicina , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/psicología , Neoplasias Pancreáticas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/psicología , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/terapia , Predisposición Genética a la Enfermedad/psicología , Medición de Riesgo , Anciano , Ansiedad/psicología , Ansiedad/diagnóstico , Ansiedad/etiología , Adulto , Depresión/diagnóstico , Depresión/genética , Depresión/psicología , Asesoramiento Genético/psicología , Mutación de Línea Germinal , Familia/psicologíaRESUMEN
OBJECTIVE: We examined how responsibility (the "duty to inform relatives about genetic testing results") is understood and enacted among Swiss and Korean women carrying BRCA1 or BRCA2 pathogenic variants. METHODS: In-depth interviews and/or focus groups with 46 Swiss and 22 Korean carriers were conducted, using an identical interview guide. Data were analyzed inductively and translated into English for cross-country comparisons. RESULTS: We identified five modes of responsibility in both samples: Persuader, Enabler, Relayer, Delayer, and Decliner. The Enabler and Relayer modes were the most common in both countries. They followed the rational imperative of health and norms of competence and self-determination, respectively. The Relayer mode transmitted information without trying to influence relatives' decisions. The Delayer and Decliner modes withheld information, deeming it the best way to safeguard the family during that specific moment of its trajectory. Responsibility to disclose testing results was influenced by culturally diverging conceptions of the family unit and socio-contextual norms. CONCLUSION: Responsibility primarily reflects the imperative of health prevention; findings demonstrate various interpretations, including the sense of family caring achieved through controlled disclosure of genetic information. PRACTICE IMPLICATIONS: Findings offer healthcare providers socio-anthropological insights to assist probands navigate the disclosure of genetic information within their families. TRIAL REGISTRATION NUMBER: NCT04214210 (registered Nov 2, 2020), KCT 0005643 (registered Nov 23, 2020).
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Predisposición Genética a la Enfermedad , Neoplasias , Humanos , Femenino , Suiza , Pruebas Genéticas , Neoplasias/diagnóstico , Neoplasias/genética , República de Corea , FamiliaRESUMEN
Inherited cardiovascular diseases cover the inherited cardiovascular disease familial hypercholesterolemia and inherited cardiac diseases, like inherited cardiomyopathies and inherited arrhythmia syndromes. Cascade genetic counseling and testing in inherited cardiovascular diseases have had three decades of academic attention. Inherited cardiovascular diseases affect around 1-2% of the population worldwide and cascade genetic counseling and testing are considered valuable since preventive measures and/or treatments are available. Cascade genetic counseling via a family-mediated approach leads to an uptake of genetic counseling and testing among at-risk relatives of around 40% one year after identification of the causal variant in the proband, with uptake remaining far from complete on the long-term. These findings align with uptake rates among relatives at-risk for other late onset medically actionable hereditary diseases, like hereditary cancer syndromes. Previous interventions to increase uptake have focused on optimizing the process of informing relatives through the proband and on contacting relatives directly. However, despite successful information dissemination to at-risk relatives, these approaches had little or no effect on uptake. The limited research into the barriers that impede at-risk relatives from seeking counseling has revealed knowledge, attitudinal, social and practical barriers but it remains unknown how these factors contribute to the decision-making process for seeking counseling in at-risk relatives. A significant effect on uptake of genetic testing has only been reached in the setting of familial hypercholesterolemia, where active information provision was accompanied by a reduction of health-system-related barriers. We propose that more research is needed on barriers -including health-system-related barriers- and how they hinder counseling and testing in at-risk relatives, so that uptake can be optimized by (adjusted) interventions.
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Enfermedades Cardiovasculares , Asesoramiento Genético , Pruebas Genéticas , Humanos , Pruebas Genéticas/métodos , Enfermedades Cardiovasculares/genética , Predisposición Genética a la EnfermedadRESUMEN
Purpose: To evaluate rates of familial disclosure of hereditary cancer syndrome information. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO no.: CRD42020134276). Key electronic databases were searched to identify studies evaluating hereditary cancer syndrome cascade relative disclosure. Eligible studies were subjected to meta-analysis. Results: Thirty-four studies met inclusion criteria. Among 11,711 included relatives, 70% (95% CI 60 - 78%) were informed of their risk of carrying a cancer-associated pathogenic variant; of 2,875 relatives informed of their risk who were evaluated for uptake of cascade testing, 43% (95% CI 27 - 61%) completed testing. Rates of disclosure were higher among female vs male relatives (79% [95% CI 73% - 84%] vs 67% [95% CI 57% - 75%]) and first-degree vs second-degree relatives (83% [95% CI 77% - 88%] vs 58% [95% CI 45 - 69%]). Conclusion: Nearly one-third of at-risk relatives remain uninformed of their risk of carrying a cancer-associated pathogenic variant. Even among those informed, fewer than half subsequently complete genetic testing, representing a critical missed opportunity for precision cancer prevention. Innovation: Five studies evaluating interventions to improve disclosure rates were generally ineffective. Urgent work is needed to elucidate barriers to relative disclosure by probands to develop targeted interventions that can optimize proband-mediated cascade genetic testing rates.
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Background: Hereditary breast and ovarian cancer and Lynch syndrome are associated with increased lifetime risk for common cancers. Offering cascade genetic testing to cancer-free relatives of individuals with HBOC or LS is a public health intervention for cancer prevention. Yet, little is known about the utility and value of information gained from cascade testing. This paper discusses ELSI encountered during the implementation of cascade testing in three countries with national healthcare systems: Switzerland, Korea, and Israel. Methods: A workshop presented at the 5th International ELSI Congress discussed implementation of cascade testing in the three countries based on exchange of data and experiences from the international CASCADE cohort. Results: Analyses focused on models of accessing genetic services (clinic-based versus population-based screening), and models of initiating cascade testing (patient-mediated dissemination versus provider-mediated dissemination of testing results to relatives). The legal framework of each country, organization of the healthcare system, and socio-cultural norms determined the utility and value of genetic information gained from cascade testing. Conclusion: The juxtaposition of individual versus public health interests generates significant ELSI controversies associated with cascade testing, which compromise access to genetic services and the utility and value of genetic information, despite national healthcare/universal coverage.
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PURPOSE: Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic diabetes. Despite its autosomal dominant inheritance, many MODY participants in the University of Chicago Monogenic Diabetes Registry have no family members enrolled. We aimed to gather data on the Registry participants' experiences in (1) receipt of an accurate diagnosis, (2) decisions regarding disclosure of their MODY genetic test results with biological relatives, and (3) recommendations toward our Registry's processes and outreach. METHODS: We conducted 20 one-on-one semistructured interviews with adult Registry participants. RESULTS: All participants found navigating the health care system challenging because of the providers' unfamiliarity with MODY and dismissal of its importance post diagnosis. All had shared their results with at least 1 relative, however many found their relatives resistant to engaging with their providers. Participants wanted to receive targeted information on their condition and connect with other participants who have faced similar diagnostic and treatment challenges. CONCLUSION: Our results demonstrate that our probands faced resistance to reclassification of their diabetes from both health care providers and relatives. In an effort to improve cascade testing, the Registry is designing a portal to facilitate participant-research team communication and provide additional supports for participants to involve family members in testing.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Pruebas Genéticas , Familia , Sistema de Registros , MutaciónRESUMEN
Cascade testing for familial cancer syndromes has historically been difficult to execute. As part of a facilitated cascade testing pathway, we evaluated barriers to completion of cascade testing. Our previously published study evaluated a facilitated cascade testing pathway whereby a genetics team facilitated at-risk relative (ARR) cascade testing through telephone genetic counseling and mailed saliva kit testing. This follow-up study evaluated barriers to completion of cascade genetic testing through six-month follow-up telephone interviews. Probands identified 114 ARRs, of whom 97 were successfully contacted by telephone. Among those contacted, 83 (86%) reported interest in genetic testing and 14 (14%) declined. Among those reporting interest in testing, 71% (69/83) completed testing. Follow-up telephone interviews revealed that 14 ARRs did not complete testing despite reporting interest for the following reasons: concern about genetic discrimination, fear of a positive result and belief that the pathogenic variant was not relevant to his/her health. Five ARRs reported that they remained interested in testing and the telephone call prompted completion of testing. Even when facilitated by a medical team with prioritization of relative convenience, significant barriers to cascade testing ARRs for hereditary breast and ovarian cancer syndrome persist due to concern about genetic discrimination, cost, and fear of positive test results.
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Neoplasias de la Mama , Síndrome de Cáncer de Mama y Ovario Hereditario , Neoplasias Ováricas , Femenino , Humanos , Masculino , Síndrome de Cáncer de Mama y Ovario Hereditario/diagnóstico , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Predisposición Genética a la Enfermedad , Estudios de Seguimiento , Pruebas Genéticas , Asesoramiento Genético/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genéticaRESUMEN
Germline pathogenic variants in the tumor suppressor gene BAP1 are associated with the hereditary tumor predisposition syndrome with susceptibility to uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other cancers. Germline BAP1 pathogenic variants are rare in the non-cancer general population with an estimated carrier frequency of 1:19,898 but more common in cancer patients with a carrier frequency of 1:1299. In the following we present the first report of a family with two unique BAP1 pathogenic variants. Retrospective case report of a family with two unique pathogenic variants in BAP1. A male (proband) was referred to our ocular oncology clinic for second opinion for his multiple independent uveal melanomas at ages 65, 68 and 71. Given his personal history of squamous cell carcinoma at age 61, renal cell carcinoma at age 63, and family history of atypical meningioma, basal cell carcinoma, pancreatic and prostate cancers he was assessed for germline pathogenic variants in BAP1 through our ongoing research study. Sanger sequencing identified the American founder pathogenic variant, c.1717delC, pL573Wfs*3, that was confirmed in a clinical laboratory. Both the proband's brother and nephew tested negative for the familial variant through single site cascade genetic testing. However, based on the personal history of multiple basal cell carcinoma in the nephew and family history of pancreatic and laryngeal cancers (both not known to be associated with BAP1-TPDS), a large cancer panel testing was recommended for the nephew. His panel testing revealed a different BAP1 pathogenic variant, c.605G>A, p. Trp202*. This variant was not detected in the proband or the proband's brother. Based on the frequency of germline BAP1 variants in the cancer population, the chance of occurrence of two different BAP1 variants in a family with cancer history is 5.9 × 10-7. This case report provides support for the importance of offering large panel cascade genetic testing, rather than single site testing for only the family pathogenic variant, for all at risk family members especially when the family variant cannot explain all the cancers in the family.
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Carcinoma de Células Renales , Neoplasias Renales , Melanoma , Síndromes Neoplásicos Hereditarios , Neoplasias Cutáneas , Humanos , Masculino , Persona de Mediana Edad , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/genética , Predisposición Genética a la Enfermedad , Estudios Retrospectivos , Proteínas Supresoras de Tumor/genética , Mutación de Línea Germinal , Síndromes Neoplásicos Hereditarios/genética , Ubiquitina Tiolesterasa/genéticaRESUMEN
Introduction: Efforts are needed across disciplines to close disparities in genomic healthcare. Nurses are the most numerous trained healthcare professionals worldwide and can play a key role in addressing disparities across the continuum of care. ACCESS is an empirically-based theoretical framework to guide clinical practice in order to ameliorate genomic disparities. Methods: The framework was developed by the International Nursing CASCADE Consortium based on evidence collected between 2005 and 2023 from individuals and families of various ethnic backgrounds, with diverse hereditary conditions, and in different healthcare systems, i.e., Israel, Korea, Switzerland, and several U.S. States. The components of the framework were validated against published scientific literature. Results: ACCESS stands for Advocating, Coping, Communication, cascadE Screening, and Surveillance. Each component is demonstrated in concrete examples of clinical practice within the scope of the nursing profession related to genomic healthcare. Key outcomes include advocacy, active coping, intrafamilial communication, cascade screening, and lifelong surveillance. Advocacy entails timely identification of at-risk individuals, facilitating referrals to specialized services, and informed decision-making for testing. Active coping enhances lifelong adaptation and management of disease risk. Effective intrafamilial communication of predisposition to hereditary disease supports cascade testing of unaffected at-risk relatives. Lifelong surveillance is essential for identifying recurrence, changes in health status, and disease trajectory for life-threatening and for life-altering conditions. Discussion: ACCESS provides a standardized, systematic, situational, and unifying guide to practice and is applicable for nursing and for other healthcare professions. When appropriately enacted it will contribute towards equitable access to genomic resources and services.
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Background: An alternative to population-based genetic testing, automated cascade genetic testing facilitated by sharing of family health history, has been conceptualized as a more efficient and cost-effective approach to identify hereditary genetic conditions. However, existing software and applications programming interfaces (API) for the practical implementation of this approach in health care settings have not been described. Methods: We reviewed API available for facilitating cascade genetic testing in electronic health records (EHRs). We emphasize any information regarding informed consent as provided for each tool. Using semi-structured key informant interviews, we investigated uptake of and barriers to integrating automated family cascade genetic testing into the EHR. Results: We summarized the functionalities of six tools related to utilizing family health history to facilitate cascade genetic testing. No tools were explicitly capable of facilitating family cascade genetic testing, but few enterprise EHRs supported family health history linkage. We conducted five key informant interviews with four main considerations that emerged including: 1) incentives for interoperability, 2) HIPAA and regulations, 3) mobile-app and alternatives to EHR deployment, 4) fundamental changes to conceptualizing EHRs. Discussion: Despite the capabilities of existing technology, limited bioinformatic support has been developed to automate processes needed for family cascade genetic testing and the main barriers for implementation are nontechnical, including an understanding of regulations, consent, and workflow. As the trade-off between cost and efficiency for population-based and family cascade genetic testing shifts, the additional tools necessary for their implementation should be considered.
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BACKGROUND: Uptake of cancer risk management based on inherited predispositions, which encompasses bilateral mastectomy (BLM), bilateral salpingo-oophorectomy (BSO), and intensified screening, is the primary motivation for cascade testing for hereditary breast and ovarian cancer (HBOC). However, long-term outcome data for cascade testers are lacking. METHODS: Medical records were abstracted for all unaffected women with pathogenic variants in HBOC genes from 2 cancer hospitals (2013-2019) with at least 1 year of follow-up to compare the uptake of surgery and screening between cascade and noncascade testers. RESULTS: Cascade testers (79.8%) were younger than noncascade testers (mean age, 37.6 vs 43.5 years; P = .002). Among women aged ≥40 years, 43% underwent BLM, and 71.6% underwent BSO, with no significant difference in uptake between cascade and noncascade testers. The mean time to BSO among cascade testers was shorter among women aged ≥40 years versus those aged <40 years (11.8 vs 31.9 months; P = .04); no such difference was observed among noncascade testers. Mammography and breast magnetic resonance imaging rates were low in the recorded 6 years for both groups after genetic counseling. CONCLUSIONS: Management uptake among cascade testers is high with rates comparable to those for unaffected BRCA-positive women. A large proportion of women act on cascade test results, and this represents a novel report of utilization of cancer management strategies.
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Neoplasias de la Mama , Neoplasias Ováricas , Adulto , Neoplasias de la Mama/diagnóstico , Femenino , Pruebas Genéticas , Humanos , Mastectomía , Mutación , Neoplasias Ováricas/genética , Gestión de Riesgos , SalpingooforectomíaRESUMEN
We compared a tailored and a targeted intervention designed to increase genetic testing, clinical breast exam (CBE), and mammography in young breast cancer survivors (YBCS) (diagnosed <45 years old) and their blood relatives. A two-arm cluster randomized trial recruited a random sample of YBCS from the Michigan cancer registry and up to two of their blood relatives. Participants were stratified according to race and randomly assigned as family units to the tailored (n = 637) or the targeted (n = 595) intervention. Approximately 40% of participants were Black. Based on intention-to-treat analyses, YBCS in the tailored arm reported higher self-efficacy for genetic services (p = 0.0205) at 8-months follow-up. Genetic testing increased approximately 5% for YBCS in the tailored and the targeted arm (p ≤ 0.001; p < 0.001) and for Black and White/Other YBCS (p < 0.001; p < 0.001). CBEs and mammograms increased significantly in both arms, 5% for YBCS and 10% for relatives and were similar for Blacks and White/Others. YBCS and relatives needing less support from providers reported significantly higher self-efficacy and intention for genetic testing and surveillance. Black participants reported significantly higher satisfaction and acceptability. Effects of these two low-resource interventions were comparable to previous studies. Materials are suitable for Black women at risk for hereditary breast/ovarian cancer (HBOC).
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Pathogenic germline variants in Breast Cancer 1/2 (BRCA) genes confer increased cancer risk. Understanding BRCA status/risk can enable family cascade screening and improve cancer outcomes. However, more than half of the families do not communicate family cancer history/BRCA status, and cancer outcomes differ according to parent of origin (i.e., maternally vs. paternally inherited pathogenic variant). We aimed to explore communication patterns around family cancer history/BRCA risk according to parent of origin. We analyzed qualitative interviews (n = 97) using template analysis and employed the Theory of Planned Behavior (TPB) to identify interventions to improve communication. Interviews revealed sub-codes of 'male stoicism and 'paternal guilt' that impede family communication (template code: gender scripting). Conversely, 'fatherly protection' and 'female camaraderie' promote communication of risk. The template code 'dysfunctional family communication' was contextualized by several sub-codes ('harmful negligence', 'intra-family ignorance' and 'active withdrawal of support') emerging from interview data. Sub-codes 'medical misconceptions' and 'medical minimizing' deepened our understanding of the template code 'medical biases'. Importantly, sub-codes of 'informed physicians' and 'trust in healthcare' mitigated bias. Mapping findings to the TPB identified variables to tailor interventions aimed at enhancing family communication of risk and promoting cascade screening. In conclusion, these data provide empirical evidence of the human factors impeding communication of family BRCA risk. Tailored, theory-informed interventions merit consideration for overcoming blocked communication and improving cascade screening uptake.
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Sudden cardiac death due to heritable ventricular arrhythmias is an important cause of mortality, especially in young healthy individuals. The identification of the genetic basis of Mendelian diseases associated with arrhythmia has allowed the integration of this information into the diagnosis and clinical management of patients and at-risk family members. The rapid expansion of genetic testing options and the increasing complexity involved in the interpretation of results creates unique opportunities and challenges. There is a need for competency to incorporate genetics into clinical management and to provide appropriate family-based risk assessment and information. In addition, disease-specific genetic knowledge is required to order and correctly interpret and apply genetic testing results. Importantly, genetic diagnosis has a critical role in the risk stratification and clinical management of family members. This review summarizes the approach to genetic counseling and genetic testing for inherited arrhythmias and highlights specific genetic principles that apply to long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.
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Arritmias Cardíacas/genética , Muerte Súbita Cardíaca/etiología , Electrocardiografía , Asesoramiento Genético/métodos , Pruebas Genéticas/métodos , Sistema de Conducción Cardíaco/fisiopatología , Medición de Riesgo/métodos , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/diagnóstico , Muerte Súbita Cardíaca/epidemiología , Salud Global , Humanos , Incidencia , Tasa de Supervivencia/tendenciasRESUMEN
Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high-grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer.