ABSTRACT
BACKGROUND: Germline genetic testing is recommended for men with metastatic or high-risk prostate cancer to inform treatment and risk management for other cancers and inform genetic testing in at-risk relatives. However, relatively few patients with prostate cancer undergo genetic testing. Given the low rate of testing and increasing demands on genetic service providers, strategies are needed that reduce barriers to testing while conserving genetic counseling resources. The primary goal of this study was to determine whether a proactive and streamlined "traceback" approach could yield increased genetic testing participation among prostate cancer survivors. METHODS: We randomized 107 survivors of metastatic and high-risk prostate cancer to streamlined testing (ST) versus enhanced usual care (EUC). ST participants were proactively provided with print genetic education materials and the option to proceed to genetic testing without pre-test genetic counseling. EUC participants were sent a letter from their physician advising them of their eligibility for genetic testing and recommending they schedule genetic counseling. The primary outcome was genetic testing participation. Secondary outcomes were distress, knowledge, decision satisfaction, and regret. RESULTS: In the ST group, 41.5% of participants completed genetic testing compared with 27.8% in the EUC group. After adjusting for education and marital status, the odds of testing were more than twice as high for the ST group as for the EUC group (odds ratio, 2.57; 95% CI, 1.05-6.29). The groups did not differ on any of the psychosocial outcomes at the 3-month follow-up. CONCLUSIONS: Proactive outreach paired with streamlined genetic testing delivery may be a safe, effective, and resource-efficient approach to facilitate traceback genetic testing in prostate cancer survivors.
Subject(s)
Cancer Survivors , Prostatic Neoplasms , Humans , Male , Genetic Counseling , Genetic Testing , Mutation , Pilot Projects , Prostate , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/geneticsABSTRACT
BACKGROUND: Previous studies describing genetics evaluation in spontaneous coronary artery dissection (SCAD) have been retrospective in nature or presented as single case reports. As part of a dedicated clinical program, we evaluated patients in cardiovascular genetics clinic to determine the role of genetically triggered vascular disease and genetic testing in SCAD. METHODS AND RESULTS: Patient data were entered prospectively into the Massachusetts General Hospital SCAD registry database from July 2013 to September 2017. Clinically indicated genetic testing was conducted based on patient imaging, family history, physical examination, and patient preference. Of the 107 patients enrolled in the registry, 73 underwent cardiovascular genetics evaluation at our center (average age, 45.3±9.4 years; 85.3% female), and genetic testing was performed for 44 patients. A family history of aneurysm or dissection was not a prevalent feature in the study population, and only 1 patient had a family history of SCAD. Six patients (8.2%) had identifiable genetically triggered vascular disease: 3 with vascular Ehlers-Danlos syndrome (COL3A1), 1 with Nail-patella syndrome (LMX1B), 1 with autosomal dominant polycystic kidney disease (PKD1), and 1 with Loeys-Dietz syndrome (SMAD3). None of these 6 had radiographic evidence of fibromuscular dysplasia. CONCLUSIONS: In this series, 8.2% of the SCAD patients evaluated had a molecularly identifiable disorder associated with vascular disease. The most common diagnosis was vascular Ehlers-Danlos syndrome. Patients with positive gene testing were significantly younger at the time of their first SCAD event. A low threshold for genetic testing should be considered in patients with SCAD.
Subject(s)
Coronary Vessel Anomalies/genetics , DNA Mutational Analysis/methods , Genetic Testing/methods , Mutation , Vascular Diseases/congenital , Adult , Boston , Coronary Vessel Anomalies/diagnostic imaging , Databases, Factual , Female , Genetic Association Studies , Genetic Markers , Genetic Predisposition to Disease , Heredity , Hospitals, General , Humans , Male , Middle Aged , Pedigree , Phenotype , Predictive Value of Tests , Prospective Studies , Registries , Risk Factors , Tertiary Care Centers , Vascular Diseases/diagnostic imaging , Vascular Diseases/geneticsABSTRACT
Weill-Marchesani syndrome (WMS) is a rare form of acromelic dysplasia that is characterized by distinctive skeletal, ocular, and cardiovascular abnormalities. Previously described cardiac manifestations of WMS include aortic and pulmonary valve stenosis, mitral valve prolapse, mitral stenosis, and QTc prolongation. Autosomal dominant forms of WMS result from heterozygous pathogenic variants in FBN1, a gene with a well characterized role in the pathogenesis of thoracic aortic aneurysm (TAA) in the context of Marfan syndrome. In contrast, only one patient has been reported with aortic disease in WMS. Although the risk of aortic dissection from preceding TAA remains the leading cause of morbidity for individuals with Marfan syndrome, rare reports of arterial dissection in the peripheral vasculature have been described. Peripheral artery dissection has not been previously reported in other FBN1-related diseases. We describe a three generation family with FBN1-related WMS whose cardiovascular manifestations include TAA and cervical artery dissection, thus expanding the cardiovascular phenotype of WMS. Further research is required to quantify these risks and establish appropriate recommendations for cardiovascular imaging, medical management, and prophylactic surgical intervention in individuals with FBN1--related acromelic dysplasia.
