Influence of Genetic Counseling Graduate Program Websites on Student Application Decisions.

This study investigated how genetic counseling educational program websites affect application decisions via an online survey sent to current students and recent graduates. Program leadership: directors, assistant directors, associate directors, were also surveyed to determine where their opinions coincided or differed from those reported by students and recent graduates. Chi square analysis and t-tests were used to determine significance of results. A two-sample t-test was used to compare factors students identified as important on a 5-point Likert scale with those identified by directors. Thematic analysis revealed three major themes students consider important for program websites: easy navigation, website content, and website impression. Directors were interested in how prospective students use their program website and what information they found most useful. Students indicated there were specific programs they chose not to apply to due to the difficulty of using the website for that program. Directors significantly underestimated how important information about application requirements was to students in making application decisions. The information reported herein will help individual genetic counseling graduate programs improve website functionality and retain interested applicants.

Genetic Counseling Milestones: A Framework for Student Competency Evaluation.

Graduate medical education has recently increased focus on the development of medical specialty competency milestones to provide a targeted tool for medical resident evaluation. Milestones provide developmental assessment of the attainment of competencies over the course of an educational program. An educational framework is described to explore the development of Genetic Counseling Milestones for the evaluation of the development of genetic counseling competencies by genetic counseling students. The development of Genetic Counseling Milestones may provide a valuable tool to assess genetic counseling students across all program activities. Historical educational context, current practices, and potential benefits and challenges in the development of Genetic Counseling Milestones are discussed.

Duchenne Muscular Dystrophy: a Survey of Perspectives on Carrier Testing and Communication Within the Family.

Carrier testing is widely available for multiple genetic conditions, and several professional organizations have created practice guidelines regarding appropriate clinical application and the testing of minors. Previous research has focused on carrier screening, predictive testing, and testing for X-linked conditions. However, family perspectives on carrier testing for X-linked lethal diseases have yet to be described. In this study, we explored communication within the family about carrier testing and the perspectives of mothers of sons with an X-linked lethal disease, Duchenne muscular dystrophy (DMD). Twenty-five mothers of sons with DMD participated in an anonymous online survey. Survey questions included multiple choice, Likert scale, and open ended, short answer questions. Analysis of the multiple choice and Likert scale questions revealed that most mothers preferred a gradual style of communication with their daughters regarding risk status. In addition, most participants reported having consulted with a genetic counselor and found it helpful. Comparisons between groups, analyzed using Fisher's exact tests, found no differences in preferred style due to mother's carrier status or having a daughter. Thematic analysis was conducted on responses to open ended questions. Themes identified included the impact of family implications, age and maturity, and a desire for autonomy regarding the decision to discuss and undergo carrier testing with at-risk daughters, particularly timing of these discussions. Implications for genetic counseling practice are discussed.

Evolving Roles of Genetic Counselors in the Clinical Laboratory.

Genetic counselors (GCs) possess several core competencies that provide direct benefit in the clinical laboratory setting. Communication with clients about complex information such as test methodology or results and the skills of facilitation and translation of complex information were recognized as important skills early in the establishment of GCs in laboratories. The clinical expertise of GCs serves as the background and experience from which they facilitate complex laboratory cases. Early roles for GCs in the laboratory also included result reporting, case management, and test development. The scope of roles has broadened to include management, business development, education, telemedicine, research, and variant interpretation. With increasing value being placed on genetic counseling skills both in and outside of a clinical laboratory, the roles and positions of GCs will likely continue to expand.

Prenatal cell-free DNA screening for fetal aneuploidy in pregnant women at average or high risk: Results from a large US clinical laboratory.

BACKGROUND: We evaluated the performance of a cell-free DNA (cfDNA) prenatal screening assay for trisomies 21, 18, and 13, and sex chromosome aneuploidies (SCAs) among a population of pregnant women that included both those at average and high risk. METHODS: Specimen collection, cfDNA extraction, massively parallel sequencing, and bioinformatics analysis were conducted per laboratory protocol. Assay results, concordance with pregnancy outcomes, and performance characteristics were evaluated. RESULTS: A total 75,658 specimens from 72,176 individual pregnant women were received. Technical reasons accounted for 288 (0.4% of all received samples) tests not performed. In the final analysis cohort (N = 69,794), 13% of pregnancies were considered at average risk and 87% at high risk. Mean gestational age at specimen collection was 15.1 weeks. Of the 69,794 unique pregnancies, 1,359 (1.9%) had positive test results. Among the results with confirmed outcomes, PPV for trisomies 21, 18, and 13 was 98.1%, 88.2%, and 59.3%, respectively; the PPV was 69.0% for SCAs and 75.0% for microdeletions. Overall, PPV was 87.2%, sensitivity was 97.9%, and specificity was 99.9%. CONCLUSION: This cfDNA prenatal screening assay provides highly accurate discrimination between affected and unaffected pregnancies among a population of pregnant women at average and high risk for fetal genetic abnormalities.

Molecular characterization of 20 small supernumerary marker chromosome cases using array comparative genomic hybridization and fluorescence in situ hybridization.

The variability of a small supernumerary marker chromosome (sSMC)-related phenotype is determined by the molecular component, the size, and shape of the marker chromosome. As fluorescence in situ hybridization has limitations regarding the resolution, efficiency, and accuracy. Recently, array comparative genomic hybridization (aCGH) was used for sSMC characterization. In this study, twenty cases with sSMCs were characterized by aCGH and FISH. Chromosomal origin of the marker chromosomes were successfully identified in seventeen of them. For the three cases with negative aCGH results, two of them were more likely due to that the sSMCs only contained centromere heterochromatin, whereas the reason for the remaining case with negative aCGH finding was uncertain. In order to establish a stronger genotype-phenotype correlation for clinical service in the future and avoid miss characterization, more sSMC cases were needed to be detailed characterized. This will help to clarify the variable clinical characteristics of sSMCs and provide additional information to aid clinical service and future research.

Clinical report: variable phenotypic expression in a large sibling cohort with a deletion of 4p16.1.

We report a half-sibling cohort with deletion of 4p16.1, astigmatism, gross and fine motor delay, variable intellectual disability, and variable behavioral concerns. However, two siblings without the deletion also had learning delays and psychological concerns. Thus, variable phenotypic expression was seen and the significance of deletion of 4p16.1 remains unclear.

Two patients with small chromosome 22q11.21 alterations and central nervous system abnormalities.

BACKGROUND: Central nervous system features have been rarely described to be associated with the small deletion or duplication of chromosome 22q11.21. CASE PRESENTATION: We report two patients with chromosome 22q11.21 alterations and central nervous system abnormalities. Features described include semilobar holoprosencephaly in the patient with the small deletion and Chiari I malformation in the patient with the small duplication. CONCLUSIONS: This report will aid in the characterization of the clinical significance of interstitial duplications and deletions on the long-arm of chromosome 22. Areas of future research would benefit from additional analysis of the described regions with inclusion of the phenotypic findings described in this case report to provide additional insight into the pathogenicity of the described alterations.

16p13.3 duplication associated with non-syndromic pierre robin sequence with incomplete penetrance.

BACKGROUND: Pierre Robin sequence (PRS) is a condition present at birth. It is characterized by micrognathia, cleft palate, upper airway obstruction, and feeding problems. Multiple etiologies including genetic defects have been documented in patients with syndromic, non-syndromic, and isolated PRS. CASE PRESENTATION: We report a 4-year-old boy with a complex small supernumerary marker chromosome (sSMC) who had non-syndromic Pierre Robin sequence (PRS). The complex marker chromosome, der(14)t(14;16)(q11.2;p13.13), was initially identified by routine chromosomal analysis and subsequently characterized by array-comparative genomic hybridization (array CGH) and confirmed by fluorescence in situ hybridization (FISH). Clinical manifestations included micrognathia, U-type cleft palate, bilateral congenital ptosis, upslanted and small eyes, bilateral inguinal hernias, umbilical hernia, bilateral clubfoot, and short fingers and toes. To our best knowledge, this was the first case diagnosed with non-syndromic PRS associated with a complex sSMC, which involved a 3.8 Mb gain in the 14q11.2 region and an 11.8 Mb gain in the 16p13.13-pter region. CONCLUSIONS: We suggest that the duplicated chromosome segment 16p13.3 possibly may be responsible for the phenotypes of our case and also may be a candidate locus of non-syndromic PRS. The duplicated CREBBP gene within chromosome 16p13.3 is associated with incomplete penetrance regarding the mandible development anomalies. Further studies of similar cases are needed to support our findings.