The impact of utilization of early aneuploidy screening on amniocenteses available for training in obstetrics and fetal medicine.

OBJECTIVE: First-trimester aneuploidy screening has high detection rates and low false-positive rates. Their use as well as the implementation of non-invasive prenatal testing may affect specialty training in prenatal diagnosis procedures. STUDY DESIGN: Descriptive study of first-trimester aneuploidy screening and amniocentesis in an obstetric training program. Screening methods were tracked from their introduction in 2004 through 2011. The volume of amniocentesis procedures from 2000 to 2011 was evaluated. RESULTS: First-trimester screening tests increased from 283 to 1225 between 2005 and 2011, whereas genetic amniocenteses declined from 460 to 168 during the same period. The percent of older women who chose a first-trimester screen test rose from 12.7% to 44.2% CONCLUSION: First-trimester screening options reduce genetic amniocenteses available for training. Fetal medicine and general obstetrics training programs need to evaluate their clinical experience and determine whether simulation training methods are needed for education.

The Development of an Infrastructure to Facilitate the Use of Whole Genome Sequencing for Population Health.

The clinical use of genomic analysis has expanded rapidly resulting in an increased availability and utility of genomic information in clinical care. We have developed an infrastructure utilizing informatics tools and clinical processes to facilitate the use of whole genome sequencing data for population health management across the healthcare system. Our resulting framework scaled well to multiple clinical domains in both pediatric and adult care, although there were domain specific challenges that arose. Our infrastructure was complementary to existing clinical processes and well-received by care providers and patients. Informatics solutions were critical to the successful deployment and scaling of this program. Implementation of genomics at the scale of population health utilizes complicated technologies and processes that for many health systems are not supported by current information systems or in existing clinical workflows. To scale such a system requires a substantial clinical framework backed by informatics tools to facilitate the flow and management of data. Our work represents an early model that has been successful in scaling to 29 different genes with associated genetic conditions in four clinical domains. Work is ongoing to optimize informatics tools; and to identify best practices for translation to smaller healthcare systems.

Population prevalence of individuals meeting criteria for hereditary breast and ovarian cancer testing.

BACKGROUND: Personal cancer diagnosis and family cancer history factor into which individuals should undergo genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome. Family history is often determined in the research setting through kindreds with disease clusters, or clinically from self-report. The population prevalence of individuals with diagnostic characteristics and/or family cancer history meeting criteria for HBOC testing is unknown. METHODS: Utilizing Surveillance, Epidemiology, and End Results (SEER) cancer registry data and a research resource linking registry records to genealogies, the Utah Population Database, the population-based prevalence of diagnostic and family history characteristics meeting National Comprehensive Cancer Network (NCCN) criteria for HBOC testing was objectively assessed. RESULTS: Among Utah residents with an incident breast cancer diagnosis 2010-2015 and evaluable for family history, 21.6% met criteria for testing based on diagnostic characteristics, but the proportion increased to 62.9% when family history was evaluated. The proportion of cases meeting testing criteria at diagnosis was 94% for ovarian cancer, 23% for prostate cancer, and 51.1% for pancreatic cancer. Among an unaffected Utah population of approximately 1.7 million evaluable for family history, 197,601 or 11.6% met testing criteria based on family history. CONCLUSIONS: This study quantifies the population-based prevalence of HBOC criteria using objectively determined genealogy and cancer incidence data. Sporadic breast cancer likely represents a portion of the high prevalence of family cancer history seen in this study. These results underline the importance of establishing presence of a deleterious mutation in an affected family member, per NCCN guidelines, before testing unaffected relatives.

Probable second fetus with Marles-Chudley syndrome: cardiac calcifications with ulnar deficiency and absent/hypoplastic thumbs.

In 1990 Marles and Chudley reported on an infant with absent ulnae and concomitant radial hypoplasia, oligodactyly, hydropsfetalis, and apparent endocardial fibroelastosis (EFE) and, on the basis of phenotype and parental consanguinity, postulated autosomal recessive inheritance. Recently we were privileged to study parts of a fetus who had presented at ultrasonography with cardiac calcifications, micrognathia, and severe ulnar dysgenesis. The small pieces of heart we received showed neither endocardial fibroelastosis nor calcifications. Thus, we had initial doubts that we were dealing with the Marles-Chudley syndrome. However, a review by Chudley of the heart findings in his cases did show the calcifications usually seen in primary or secondary EFE. The parents of Dr. Chudley's patient were Flipino; the father of our patient was a Samoan. This suggests that there exists a gene for autosomal recessive Marles-Chudley syndrome in the Poynesian population with pleiotropic effects on upper limb development and cardiac histogenesis.