OBJECTIVETo identify genetic and nongenetic factors contributing to the risk of bladder exstrophyepispadias complex (BEEC). PATIENTS AND METHODSIn all, 285 families with BEEC were invited to participate in the study, and 232 of them were recruited. Epidemiological information was obtained from 151 of the consenting families, with a detailed clinical genetic examination of 94 probands. In all, 440 DNA samples were collected from 163 families for molecular analysis.

Background Next-generation sequencing enables testing for multiple genes simultaneously (“panel-based testing”) as opposed to sequential testing for one inherited condition at a time (“syndrome-based testing”). The current study presents results from patients who underwent hereditary colorectal cancer (CRC) panel-based testing (“ColoNext™”). Methods De-identified data from a clinical testing laboratory were used to calculate 1) frequencies for patient demographic, clinical, and family history variables and 2) rates of pathogenic mutations and variants of uncertain significance (VUS). The proportion of individuals with a pathogenic mutation who met national syndrome-based testing criteria was also determined. Results Of 586 patients, a pathogenic mutation was identified in 10.4%, while 20.1% had at least one VUS. After removing 8 patients with CHEK2 mutations and 11 MUTYH heterozygotes, the percentage of patients with “actionable” mutations that would clearly alter cancer screening recommendations per national guidelines decreased to 7.2%. Of the 42 patients with an “actionable” result, 30 (71%) clearly met established syndrome-based testing guidelines. Conclusion This descriptive study is among the first to report on a large clinical series of patients undergoing panel-based testing for inherited CRC. Results are discussed in the context of benefits and concerns that have been raised about panel-based testing implementation.

Purpose: This study describes practitioner knowledge and practices related to BRCA testing and management and explores how training may contribute to practice patterns. Methods: A survey was mailed to all BRCA testing providers in Florida listed in a publicly available directory. Descriptive statistics characterized participants and their responses. Results: Of the 87 respondents, most were community-based physicians or nurse practitioners. Regarding BRCA mutations, the majority (96%) recognized paternal inheritance and 61% accurately estimated mutation prevalence. For a 35-year-old unaffected BRCA mutation carrier, the majority followed national management guidelines. However, 65% also recommended breast ultrasonography. Fewer than 40% recognized the need for comprehensive rearrangement testing when BRACAnalysis Ò was negative in a woman at 30% risk. Finally, fewer than 15% recognized appropriate testing for a BRCA variant of uncertain significance. Responses appeared to be positively impacted by presence and type of cancer genetics training. Conclusions: In our sample of providers who order BRCA testing, knowledge gaps in BRCA prevalence estimates and appropriate screening, testing, and results interpretation were identified. Our data suggest the need to increase regulation and oversight of genetic testing services at a policy level, and are consistent with case reports that reveal liability risks when genetic testing is conducted without adequate knowledge and training.

There is tremendous excitement about the promise of new genomic technologies to transform medical practice and improve patient care. Although the full power of genetic diagnosis has not yet been realized, paradigms of clinical decision-making are changing. In fact, recent policy level changes to promote genetic counseling by certified genetics professionals (GP) such as genetic counselors and clinical geneticists, are occurring at both the payer and state level. However, there remain opportunities to develop policies within the United States to: 1) enhance the access to the limited workforce of GPs; 2) revise reimbursement schemes such that costs to deliver these services may be recouped by institutions with GPs; and 3) protect against the potential for discrimination based on genetic information. Although many of these issues predate advances in genomic technologies, they are exacerbated by them, with increasing access and awareness as costs of testing decrease. Consequently, evolving shifts in national policies poise GPs to serve as a hub of information and may be instrumental in facilitating new models to deliver genetics-based care through promoting academic-community partnerships and interfacing with non-GPs. As we acknowledge the potential for genomics to revolutionize medical practice, the expertise of GPs may be leveraged to facilitate incorporation of this information into mainstream medicine.

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