Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.

Chromosome microarray (CMA) testing is used widely in prenatal settings. Some copy number variants (CNVs) detected using CMA are associated with variable or uncertain phenotype and/or possible neurocognitive involvement. Little is known about parenting an infant following such findings. Researchers conducted interviews with 23 mothers of infants diagnosed prenatally with a potentially pathogenic CNV to elicit perspectives on the child's development and disclosure of results to others. Interviews were audiotaped and analyzed for common themes. Most respondents reported their infants were developing typically. The majority expressed concern about their child's future development given the CNV. They reassured themselves their child was unaffected by: comparing him/her to siblings, scrutinizing the child's appearance and behavior, or following provider reassurances. Even without developmental and neurological concerns, some remained acutely observant of their child's neurocognitive development, leading to enrollment in early intervention or ongoing medical assessments. Mothers who were unconcerned stated they would likely attribute atypical behavior or developmental to the CNV. All interviewees shared the result with pediatricians, relatives, or friends, and many shared across groups. Most shared information with pregnant friends considering prenatal testing, but withheld partial or full information from family members due to stigma, lack of understanding, inability to explain the CNV, or presumptions that the child was unaffected. Research must address the long-term consequences of returning uncertain results for parent-child bonding and costs of ongoing assessment and early intervention for typically developing children. Follow up appointments will permit providers to screen for anxiety and assuage worry in the absence of symptoms. © 2016 Wiley Periodicals, Inc.

Since the first reports of SARS-CoV-2 infection from China, multiple studies have been published regarding the epidemiologic aspects of COVID-19 including clinical manifestations and outcomes. The majority of these studies have focused on respiratory complications. However, recent findings have highlighted the systemic effects of the virus, including its potential impact on the nervous system. Similar to SARS-CoV-1, cellular entry of SARS-CoV-2 depends on the expression of ACE2, a receptor that is abundantly expressed in the nervous system. Neurologic manifestations in adults include cerebrovascular insults, encephalitis or encephalopathy, and neuromuscular disorders. However, the presence of these neurologic findings in the pediatric population is unclear. In this review, the potential neurotropism of SARS-CoV-2, known neurologic manifestations of COVID-19 in children, and management of preexisting pediatric neurologic conditions during the COVID-19 pandemic are discussed.

In the originally published version of this article, Table 1 unfortunately included c.542G>A instead of c.542G>T. This mutation was correctly notated as c.

This study aims to explore how couples’ understanding of the nature and consequences of positive prenatal chromosomal microarray analysis (CMA) results impacts decision-making and concern about pregnancy. We interviewed 28 women and 12 male partners after receiving positive results and analyzed the transcripts to assess their understanding and level of concern about the expected clinical implications of results. Participant descriptions were compared to the original laboratory interpretation. When diagnosed prenatally, couples’ understanding of the nature and consequences of copy number variants (CNVs) impacts decision-making and concern. Findings suggest women, but less so partners, generally understand the nature and clinical implications of prenatal CMA results. Couples feel reassured, perhaps sometimes falsely so, when a CNV is inherited from a “normal” parent and experience considerable uncertainty when a CNV is de novo, frequently precipitating a search for additional information and guidance. Five factors influenced participants’ concern including: the pattern of inheritance, type of possible phenotypic involvement, perceived manageability of outcomes, availability and strength of evidence about outcomes associated with the CNV, and provider messages about continuing the pregnancy. A good understanding of results is vital as couples decide whether or not to continue with their pregnancy and seek additional information to assist in pregnancy decision-making.

OBJECTIVE Chromosome microarray analysis (CMA) is poised to take a significant place in the prenatal setting given its increased yield over standard karyotyping, but concerns regarding ethical and counseling challenges remain, especially associated with the risk of uncertain and incidental findings. Guidelines recommend patients receiving prenatal screening undergo genetic counseling prior to testing, but little is known about women’s specific pre- and post-testing informational needs, as well as their preference for return of various types of results. METHODS The present study surveys 199 prenatal genetic counselors who have counseled patients undergoing CMA testing and 152 women who have undergone testing on the importance of understanding pre-test information, return of various types of results, and resources made available following an abnormal finding. RESULTS Counselors and patients agree on many aspects, although findings indicate patients consider all available information very important, while genetic counselors give more varying ratings. CONCLUSION Counseling sessions would benefit from information personalized to a patient’s particular needs and a shared decision-making model, so as to reduce informational overload and avoid unnecessary anxiety. Additionally, policies regarding the return of various types of results are needed.

Clinical genome and exome sequencing (CGES) may identify variants leading to targeted management of existing conditions. Yet, CGES often fails to identify pathogenic diagnostic variants and introduces uncertainties by detecting variants of uncertain significance (VUS) and secondary findings. This study investigated how families understand findings and adjust their perspectives on CGES. As part of NIH's Clinical Sequencing Exploratory Research Consortium, children were recruited from clinics at the Children's Hospital of Pennsylvania (CHOP) and offered exome sequencing. Primary pathogenic and possibly pathogenic, and some secondary findings were returned. Investigators digitally recorded results disclosure sessions and conducted 3-month follow up interviews with 10 adolescents and a parent. An interdisciplinary team coded all transcripts. Participants were initially disappointed with findings, yet reactions evolved within disclosure sessions and at 3-month interviews toward acceptance and satisfaction. Families erroneously expected, and prepared extensively, to learn about risk for common conditions. During disclosure sessions, parents and adolescents varied in how they monitored and responded to each others reactions. Several misinterpreted, or overestimated, the utility of findings to attribute meaning and achieve closure for the CGES experience. Participants perceived testing as an opportunity to improve disease management despite results that did not introduce new treatments or diagnoses. Future research may examine whether families experience cognitive dissonance regarding discrepancies between expectations and findings, and how protective buffering minimizes the burden of disappointment on loved ones. As CGES is increasingly integrated into clinical care providers must contend with tempering family expectations and interpretations of findings while managing complex medical care.

Background While there is increasing interest in sharing genetic research results with participants, how best to communicate the risks, benefits and limitations of research results remains unclear. Methods Participants who received genetic research results answered open and closed‐ended questions about their experiences receiving results and interest in and advantages and disadvantages of a web‐based alternative to genetic counseling. Results 107 BRCA1/2 negative women with a personal or family history of breast cancer consented to receive genetic research results and 82% completed survey items about their experience. Most participants reported there was nothing they disliked (74%) or would change (85%) about their predisclosure or disclosure session (78% and 89%). They most frequently reported liking the genetic counselor and learning new information. Only 24% and 26% would not be willing to complete predisclosure counseling or disclosure of results by a web‐based alternative, respectively. The most frequently reported advantages included convenience and reduced time. Disadvantages included not being able to ask questions, the risk of misunderstanding and the impersonal nature of the encounter. Conclusion Most participants receiving genetic research results report high satisfaction with telephone genetic counseling, but some may be willing to consider self‐directed web alternatives for both predisclosure genetic education and return of results.