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Objective In 2022, the National Society of Genetic Counselors (NSGC) published a practice guideline for genetic testing and counseling for unexplained epilepsy. It is endorsed by the American Epilepsy Society and recommends genetic testing for all patients with unexplained epilepsy (prioritizing exome/genome sequencing [ES/GS] or multi‐gene panel [MGP] as first‐tier testing) and providing professional pre‐/post‐test counseling. This study investigates the alignment of neurologists' practice with this guideline and identifies barriers to implementation. Methods Neurologists who treat epilepsy in the United States completed a survey about guideline awareness, current practices, and barriers to genetic testing/counseling. Recruitment occurred through newsletters/listservs of professional organizations and public contact information. A total of, 91 participants accessed the survey, and 84 completed enough for inclusion in data analysis. Results Approximately half (43.9%, 36/82) of participants offer genetic testing to most/all their patients with unexplained epilepsy, while the other half (46.3%, 38/82) offer genetic testing only to patients with epilepsy for whom they suspect a genetic etiology. Neurologists caring for adult patients were significantly more likely than those caring for pediatric patients to fall into the latter category (χ2[1, N = 69] = 22.66, p < 0.001). When ordering genetic testing, 75.5% (n = 40/53) of participants choose MGP most often, while 20.8% (n = 11/53) choose ES/GS and 3.8% (n = 2/53) choose microarray. Barriers to genetic testing and pre‐/post‐test counseling included insurance coverage, test coordination, limited expertise, and access to a genetic counselor (GC). Barriers were more significant for adult providers. Over half of participants (56.1%, n = 46/82) were aware of the NSGC guideline, but almost all (91.3%, n = 36/82) thought it was not broadly publicized. Significance Increased insurance coverage, access to GCs, and awareness of guidelines are needed to improve access to genetic testing and counseling for unexplained epilepsies, particularly for the adult population. Plain Language Summary In 2022, the National Society of Genetic Counselors published a practice guideline recommending genetic testing and counseling for all patients with unexplained epilepsy, using exome/genome sequencing or a multi‐gene panel as the first‐tier test. This survey study examined neurologists' current practices compared to the guideline and identified barriers. A total of, 44% of participants offer genetic testing to most/all their patients, while 46% test only when they suspect a genetic cause. Adult neurologists rate most barriers higher than pediatric neurologists. Better insurance coverage and increased access to genetic counselors are key to improving access to epilepsy genetic testing and counseling.

Ludwine Messiaen and colleagues report the identification of constitutional LZTR1 mutations in individuals with schwannomatosis, an autosomal dominant inherited disorder of multiple schwannomas. Constitutional SMARCB1 mutations at 22q11.23 have been found in ∼50% of familial and <10% of sporadic schwannomatosis cases 1 . We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2 , with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ∼80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1 .

Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.

Although consensus is building that primary (PR) and secondary findings (SF) from genomic research should be offered to participants under some circumstances, data describing (1) actual choices of study participants and (2) factors associated with these choices are limited, hampering study planning. We conducted a cross-sectional analysis of choices made for return of PR and SF during informed consent by members of the first 247 families (790 individuals) enrolled in the Baylor-Hopkins Center for Mendelian Genomics, a genome sequencing study. Most (619; 78.3%) chose to receive SF and PR, 66 (8.4%) chose PR only, 65 (8.2%) wanted no results, and 40 (5.1%) chose SF only. Choosing SF was associated with an established clinical diagnosis in the proband (87.8 vs 79%, P=0.009) and European ancestry (EA) (87.7 vs 73%, P<0.008). Participants of non-European ancestry (NEA) were as likely as those of EA to choose SF when consented by a genetic counselor (GC) (82% NEA vs 88.3% EA, P=0.09) but significantly less likely when consented by a physician (67.4% NEA vs 85.4% EA, P=0.001). Controlling for proband diagnosis, individuals of NEA were 2.13-fold (95% CI: 1.11-4.08) more likely to choose SF when consented by a GC rather than a physician. Participants of NEA were 3-fold more likely than those of EA to decline all study results (14.7% NEA vs 5.4% EA, P<0.008). In this ethnically diverse population, whereas most participants desired PR and SF, more than 20% declined some or all results, highlighting the importance of research participant choice.

Telegenetics played an important role in providing genetic services to patients during the COVID-19 pandemic. In particular, at our institution, it enabled us to expand our genetic counseling and testing services to non-local family members of patients outside of our prior catchment area. However, as telegenetics continues to be utilized even as social distancing is no longer required, further information is needed regarding the impact of this modality on patient experience within cardiogenetics. This study qualitatively explored the experiences of 12 genotype positive individuals who underwent genetic counseling and testing via telegenetics during the first 22 months of the COVID-19 pandemic and compared the experiences of local vs. non-local patients. Both local and non-local participants discussed similar benefits and drawbacks to the use of technology in telegenetics and overall found the use of telegenetics and at-home genetic testing to be convenient. Both groups also noted having to make changes in their daily lives and future planning as a consequence of the positive genetic testing results. However, access to follow-up care differed between local and non-local participants, with more local participants having scheduled and attended appointments with the appropriate medical providers compared to non-local participants. Supplying non-local patients access to remote cardiogenetic testing may therefore require careful consideration in how to ensure proper follow-up care for genotype positive patients and may necessitate the involvement of national professional or patient-centered organizations to help streamline the referral process.

Genetic counselors working in a clinical setting may find themselves recruiting, enrolling, and returning results for genomic research, and existing clinical relationships with study participants may impact these research interactions. We present a qualitative study using semi-structured interviews of participants enrolled in a genome sequencing/exome sequencing (GS/ES) study at the same institution where they receive clinical care. Interviews were coded for motivations to participate and expectations of this research. The interviews revealed common motivations for participation, including altruism and hope for benefit for themselves, family members, and/or others with their condition. Additionally, themes emerged related to unintentional influence based on trust of the clinical provider that recruited them to the study. Participant trust in the enrolling provider at times appeared to extend to the study team to decide which research results to return and to do so in an appropriate format. Participants also based expectations for research results return on previous clinical genetic testing experiences, which may or may not be realistic depending on study design. It is imperative that genetic counselors enrolling patients into research studies be aware of the potential influence of their clinical relationship on potential subjects, be transparent about their role on the study team, and help set expectations about the study process, including results return.

The first practice based competencies (PBCs) for the field of genetic counseling were adopted by the American Board of Genetic Counseling (ABGC), 1996. Since that time, there has been significant growth in established and new work settings (clinical and non-clinical) and changes in service delivery models and the roles of genetic counselors. These changes prompted the ABGC to appoint a PBC Task Force in 2011 to review the PBCs with respect to their current relevance and to revise and update them as necessary. There are four domains in the revised PBCs: (I) Genetics Expertise and Analysis (II) Interpersonal, Psychosocial and Counseling Skills (III) Education and (IV) Professional Development and Practice. There are 22 competencies, each clarified with learning objectives or samples of activities and skills; a glossary is included. New competencies were added that address genomics, genetic testing and genetic counselors’ roles in risk assessment, education, supervision, conducting research and presenting research options to patients. With PBCs serving as the pre-defined abilities or outcomes of training, graduating genetic counselors will be well prepared to enter the field with a minimum level of skills and abilities. A description of the Task Force’s work, key changes and the 2013 PBCs are presented herein.

Supervision is a practice that is utilized by a variety of practitioners to hone their counseling skills. Genetic counselors have embraced the supervision process, and some seek out supervision in a group setting with peers. Researchers have described the structure and content of genetic counseling peer supervision groups, and provided evidence for the benefits of seeking peer supervision. This study aimed to describe the interpersonal aspects of one genetic counseling peer supervision group, including personality traits and group dynamics, and how those factors influenced our experiences within the group. We also describe how the process of evaluating these factors impacted us individually and collectively. There was consensus that the group was a safe and trusting one, which was united by similar goals and mutual respect. Members reported gaining insights about how their own personality functioned within the group milieu, and also how the group setting impacted them. Based on our experiences, we recommend that other peer supervision groups consider similar self-evaluations on a periodic basis, both to enhance group functioning and to allow for increased self-awareness and professional growth.

BackgroundStudies indicate that variants of uncertain significance are more common in non-European populations due to lack of a diversity in population databases. This difference has not been explored in epilepsy, which is increasingly found to be genetic in paediatric populations, and has precision medicine applications. This study examines the differences in the frequency of uncertain next-generation sequencing (NGS) results among a paediatric epilepsy cohort between ancestral groups historically under-represented in biomedical research (UBR) and represented in biomedical research (RBR).MethodsA retrospective chart review of patients with epilepsy seen at Columbia University Irving Medical Center (CUIMC). One hundred seventy-eight cases met the following criteria: (1) visited any provider within the Pediatric Neurology Clinic at CUIMC, (2) had an ICD code indicating a diagnosis of epilepsy, (3) underwent NGS testing after March 2015 and (4) had self-reported ancestry that fit into a single dichotomous category of either historically represented or under-represented in biomedical research.ResultsUBR cases had significantly higher rates of uncertain results when compared with RBR cases (79.2% UBR, 20.8% RBR; p value=0.002). This finding remained true after controlling for potential confounding factors, including sex, intellectual disability or developmental delay, epilepsy type, age of onset, number of genes tested and year of testing.ConclusionOur results add to the literature that individuals who are of ancestries historically under-represented in genetics research are more likely to receive uncertain genetic results than those of represented majority ancestral groups and establishes this finding in an epilepsy cohort.