The evolution of cancer risk assessment in the era of next generation sequencing.

Cancer genetics professionals face a new opportunity and challenge in adapting to the availability of cancer genetic testing panels, now available as a result of Next Generation Sequencing (NGS) technology. While cancer panels have been available for over a year, we believe that there is not yet enough data to create practice guidelines. Despite this, a year of experience allows us to provide our opinion on points to consider as cancer genetic counselors incorporate this testing technology into genetic counseling practice models. NGS technology offers the ability to potentially diagnose hereditary cancer syndromes more efficiently by testing many genes at once for a fraction of what it would cost to test each gene individually. However, there are limitations and additional risks to consider with these tests. Obtaining informed consent for concurrent testing of multiple genes requires that genetics professionals modify their discussions with patients regarding the potential cancer risks and the associated implications to medical management. We propose dividing the genes on each panel into categories that vary by degree of cancer risk (e.g. penetrance of the syndrome) and availability of management guidelines, with the aim to improve patient understanding of the range of information that can come from this testing. The increased risk for identifying variants of uncertain significance (VUS) when testing many genes at once must be discussed with patients. Pretest genetic counseling must also include the possibility to receive unexpected results as well as the potential to receive a result in the absence of related medical management guidelines. It is also important to consider whether a single gene test remains the best testing option for some patients. As panels expand, it is important that documentation reflects exactly which genes have been analyzed for each patient. While this technology holds the promise of more efficient diagnosis for many of our patients, it also comes with new challenges that we must recognize and address.

Genetic counseling for hereditary breast and gynecologic cancer syndromes at a community hospital.

Genetic screening and testing has been shown to be medically and emotionally beneficial for patients with a personal history or strong family history of breast, ovarian, and/or colorectal cancer. Gynecologic oncologists increasingly utilize genetic screening to modify their care and treatment plans of patients and their offspring based on inherited susceptibility to cancer. The U.S. Preventive Services Task Force (USPSTF) developed specific criteria that consider the medical, psychosocial, and ethical ramifications of genetic counseling of high-risk individuals. Genetic counseling and screening, along with early intervention, is of benefit to women with family histories suggestive of harboring breast cancer antigen (BRCA) mutations. The Western Connecticut Health Network (WCHN) Hereditary Cancer and Genetic Counseling Program provides a comprehensive cancer risk assessment and offers genetic screening as appropriate. This report describes trends in patient referrals, intake, results of genetic testing, and an expansion of services in a community-based genetic counseling program.

Phakomatosis pigmentovascularis: Implications for severity with special reference to Mongolian spots associated with Sturge-Weber and Klippel-Trenaunay syndromes.

In 1947 the term phakomatosis pigmentovascularis (PPV) was coined to represent the association of widespread, aberrant, and persistent nevus flammeus and pigmentary abnormalities. Four types of PPV have been recognized with type II (nevus flammeus and Mongolian spots) being the most common. Most early cases were of Asian or African descent. Many cases were subsequently associated with Sturge-Weber (S-W) and Klippel-Trenaunay (K-T) syndromes. Almost no literature reports have appeared in the genetic or dysmorphology literature! We present six cases of PPV in which five were either African, Asian or Hispanic, and five of six had an admixture of K-T and S-W. Four had macrocephaly, and one had microcephaly. Four had CNS abnormalities (three with hydrocephalus, one with Arnold-Chiari and one with polymicrogyria), three had mental retardation, and one had seizures. One each had thumb hypoplasia, hydronephrosis, glaucoma, coronal synostosis, and 3-4 finger syndactyly. It is our suspicion and hypothesis that in the presence of persistent, extensive and aberrant Mongolian spots, vascular abnormalities as are seen in K-T and S-W carry a worse prognosis. This may be particularly true either of children of Asian, Hispanic or African heritage or any individuals from darker pigmented skin groups.