Novel NKX2.5 variant associated with congenital heart disease and increased risk of malignant arrhythmia and sudden cardiac death.

INTRODUCTION: The NKX2.5 gene is an important cardiac developmental transcription factor, and variants in this gene are most commonly associated with CHD. However, there is an increased need to recognise associations with conduction disease and potentially dangerous ventricular arrhythmias. There is an increased risk of arrhythmia and sudden cardiac death in patients with NKX2.5 variants, an association with relatively less attention in the literature. METHODS: We created a family pedigree and reconstructed familial relationships involving numerous relatives with CHD, conduction disease, and ventricular non-compaction following the sudden death of one family member. Two informative but distantly related family members had genetic testing to determine the cause of arrhythmias via arrhythmia/cardiomyopathy gene testing, and we identified obligate genetic-positive relatives based on family relationships and Mendelian inheritance pattern. RESULTS: We identified a novel pathogenic variant in the NKX2.5 gene (c.437C > A; p. Ser146*), and segregation analysis allowed us to link family cardiac phenotypes including CHD, conduction disease, left ventricular non-compaction, and ventricular arrhythmias/sudden cardiac death. CONCLUSIONS: We report a novel NKX2.5 gene variant linking a spectrum of familial heart disease, and we also encourage recognition of the association between NKX2.5 gene and potentially dangerous ventricular arrhythmias, which will inform clinical risk stratification, screening, and management.

Effects of hypermobile Ehlers-Danlos syndrome patients on the workflow and professional satisfaction of genetic counselors.

The Ehlers-Danlos syndromes (EDS), a group of uncommon connective tissue disorders, are, paradoxically, an increasingly common referral to genetics specialists. Of the 13 types of EDS, the most common is hypermobile EDS (hEDS), which lacks a known genetic etiology and for which diagnosis is achieved via a robust set of clinical criteria. While previous investigations have characterized many clinical aspects of EDS as a syndrome and patients' lived experiences, a gap in the literature exists regarding clinicians' experience caring for these individuals. This study sought to understand the effects of hEDS patient referrals from genetic counselors' perspectives. To capture these novel views and values, we conducted semi-structured interviews with 15 participants who were members of the National Society of Genetic Counselors (NSGC) and had experience working with the hEDS patient population. Interview questions explored the frequency of hEDS referrals in their clinic, investigated their roles and responsibilities as genetic counselors when working with this population, analyzed their workflow for this indication, assessed the impacts on their professional satisfaction, and explored potential options for improving workflow and care for the hEDS patient population. Reflexive thematic analysis yielded four themes: (1) Referrals for hEDS have generally increased over time and many institutions have implemented new policies to control this influx, (2) genetic counselors' primary roles include education and addressing psychosocial matters for this population, (3) genetic counselors feel both rewarded and challenged by these referrals, and (4) genetic counselors call for more education and training on hEDS for all healthcare specialties. Our findings provide a better understanding of the goals of the hEDS patient referrals to genetics specialists and the opportunities and challenges those referrals present. Genetic counselors have specific training and skills in psychosocial counseling and communication, in some ways making them ideal care providers for this population. However, they are simultaneously a scarce resource and the complex medical issues presented by many patients with hEDS make multidisciplinary management essential. We conclude with potential avenues for improving interactions with this population.

Comparison of willingness and preference for genetic counseling via telemedicine: before vs. during the COVID-19 pandemic.

The COVID-19 pandemic required genetic counseling services, like most outpatient healthcare, to rapidly adopt a telemedicine model. Understanding the trends in patients' preferences for telemedicine relative to in-person service delivery both before and after the advent of the COVID-19 pandemic may aid in navigating how best to integrate telemedicine in a post-COVID-19 era. Our study explored how respondents' willingness to use, and preference for, telemedicine differed from before to after the onset of the COVID-19 pandemic. Respondents included patients, or their parent/guardian, seen in a general medical genetics clinic in 2018, prior to the COVID-19 pandemic, and in 2021, during the COVID-19 pandemic. Respondents were surveyed regarding their willingness to use telemedicine, preference for telemedicine relative to in-person care, and the influence of various factors. Among 69 pre-COVID-19 and 40 current-COVID-19 respondents, there was no shift in willingness to use, or preference for, telemedicine across these time periods. About half of respondents (50.6%) preferred telemedicine visits for the future. Of the 49.4% who preferred in-person visits, 79.1% were still willing to have visits via telemedicine. Predictors of these preferences included comfort with technology and prioritization of convenience of location. This study suggests that a hybrid care model, utilizing telemedicine and in-person service delivery, may be most appropriate to meet the needs of the diverse patients served. Concern for COVID-19 was not found to predict willingness or preference, suggesting that our findings may be generalizable in post-pandemic contexts.