Introduction: Before the COVID-19 public health emergency, few genetics providers used telehealth. As a response to this, many genetics providers began conducting telehealth care, referred to as telegenetics, usually with guidance from their institutions but without specific guidance related to the uniqueness of genetic services.Objectives: The Telegenetics Workgroup of the National Coordinating Center for Regional Genetics Networks convened a panel of experts in the fields of telemedicine, genetics, and genomics to review the existing literature on telegenetics and synthesize best operating practices for medical geneticists, genetic counselors, and metabolic dietitians providing telegenetics services.Methods: The group searched PubMed using the terms "telegenetics," "telemedicine + genetics," and "telehealth + genetics." The group also reviewed the Northeast Telehealth Resource Center's telegenetics webliography. Websites were searched, including the American Telemedicine Association's website, Center for Connected Health Policy, and National Telehealth Resource Center for position statements, standards documents, and guidelines. The group met frequently by videoconference and discussed the literature, and using expert consensus, the group determined best practices in providing telegenetics services.Results: These telegenetics best practices cover important aspects of telegenetics services, including, but not limited to, ongoing delivery of telegenetics services, use of special technology, legal and regulatory requirements, and considerations regarding special settings and circumstances in which telegenetics may be conducted.Conclusions: Recognizing the growing use of telegenetics and a future in which telegenetics continues to be part of the regular practice of genetics, this guide informs genetics providers of best practices for delivering telegenetics services to patients.

A breakdown of benefits and drawbacks of sponsored genetic testing that clinicians can use to help patients make informed decisions.

Telegenetics is the use of telemedicine to deliver clinical genetic services to patients. During the COVID-19 public health emergency (PHE), telegenetics was essential for the Center of Personalized Genetic Healthcare (CPGH). This study reviews and analyzes in the context of the RE-AIM framework CPGH’s rapid implementation of telegenetics and its impact. We conducted a chart review of all out-patient telegenetics encounters scheduled in CPGH during the first five weeks of the COVID-19 PHE. Data analyzed included demographics; number of encounters scheduled; subspecialties and providers; outcome of encounter (completed, cancelled, no- show); and telehealth platform used. Data were compared to data for out-patient encounters in 2019. In the first five weeks of the COVID-19 PHE, 465 virtual visits were scheduled and 428 were completed, involving all six subspecialties and 86% of CPGH providers. The no-show plus cancellation rate was significantly lower than in 2019. By week four, CPGH’s virtual visit volume was 82% of its out-patient volume during the same time period in 2019. Patients over 60 and Black patients were significantly more likely to use phone-audio only appointments. CPGH rapidly implemented telegenetic services to continue providing care to patients. We identified success factors that enabled this. However, our analysis also identified a possible “digital divide” for Black and older patients.

Abstract Advances in human genomics and genetics are revolutionizing healthcare and ushering in a new era of genetic information-based precision or personalized medical care. Despite a growing need for genetic testing and clinical and medical genetic services, there is currently a shortage of genetics professionals to support the appropriate acquisition and application of genetic information for patient care. Additionally, genetic providers are geographically maldistributed, as the vast majority is located in academic medical centers in urban and suburban locales. One approach to increase access is by the incorporation of telehealth (TH) services. While the advantages of TH are well established in other medical specialties, the uptake of such services among providers of medical genetics continues to evolve. Here, we will review various examples of telegenetics for adult patients, the delivery and regulation in the United States, and growing opportunities for the implementation of telegenetics to help address the shortage of genetics professionals and reduce the barriers to patients receiving clinical genetics and genetic counseling services in personalized precision and preventive health care.

Many genetic service providers have reported that they are unfamiliar with the complexities of billing and reimbursement. This chapter presents the "nuts and bolts" of documentation, coding, and billing for clinical genetic services and laboratory genetic services. It includes attention to requirements from the Centers for Medicare and Medicaid Services. Coverage policy and dealing with denials are also covered in the chapter.

To the Editor: We appreciate the opportunity to respond to the comments of Knoppers and colleagues1.Knoppers BM, et al. Letter: Relearning the 3 R’s: reinterpretation, Recontact, and Return of Genetic VariantsGoogle Scholar regarding the American College of Medical Genetics and Genomics (ACMG) statement, “Patient re-contact after revision of genomic test results: points to consider,”2.David KL, Best RG, Brenman LM, ACMG Social Ethical Legal Issues Committee, et al. Patient re-contact after revision of genomic test results: points to consider—a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 22 Dec 2018; https://doi.org/10.1038/s41436-018-0391-z [Epub ahead of print].Google Scholar recently e-published before print in Genetics in Medicine. The comments in Knoppers’ letter, however, reflect a misunderstanding of our document and conflate the clinical and research settings. We reiterate that the ACMG statement reflects practice oF.A.merican clinical geneticists who provide direct patient services. It does not speak to the research setting. Current American clinical and legal standards and fundamental ethical principles inform our Points to Consider. We clearly state that reasonable efforts should be made by providers (not necessarily only physicians) to contact the patient (Points to Consider #8). These efforts may encounter “resource constraints” that may be similar or dissimilar to those in the research setting. The letter of Knoppers et al. points out that the American Society of Human Genetics draft position3.Levy HP. Duty to re-contact in the research environment; the ASHG draft position statement presented ASHG Annual Meeting, San Diego, October 19, 2018.Google Scholar limits researchers’ “duty to re-contact” to the duration of the project funding. On the other hand, clinicians’ concerns that patients be properly informed of revised interpretation may extend indefinitely after the original consultation. Given the practicalities of contacting patients potentially years after the results oF.A. genetic test were first reported, it is neither reasonable nor realistic to promise more than providers can deliver. Despite best efforts on the part of laboratories and clinicians, re-contact cannot be guaranteed unless the patient initiates the process. The ACMG statement does not place sole responsibility for re-contact on anyone; rather the statement stresses a collaborative approach. As highlighted in our Points to Consider, the ACMG recognizes that its position may well evolve with developments in molecular technology and variant interpretation, electronic record and communication technology, and the legal environment. Therefore, the ACMG Points to Consider is meant as the best approach on these difficult issues in the current context of clinical care. The authors declare no conflicts of interest. Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose: This study of current conditions in medical genetics practice is designed to inform public policy development and present possible solutions for improving access to genetic services. Methods: Using the American College of Medical Genetics and Genomics Member Directory, membership directories from regional collaborative partners, listservs from national partners, and social media, a 16-question survey was electronically distributed in 2015. Results: The responses of 924 genetics professionals and related providers present a snapshot of current practice and an assessment of workforce needs. More than 92% of the respondents (837/910) are involved in clinical care. Among geneticists, 60% spend more than 51% of their time in clinical care. Geneticists reported an average of 10.2 new patients per week and 7.8 follow-up visits per week. More than 62% of geneticists said that their practices were nearly full; 9.4% said that they were not taking new patients. The survey identified more than 100 geneticists and 200 genetic counselor job vacancies. Fewer than 18% of respondents reported use of telemedicine. Conclusion: When compared with previously published workforce studies, these data show that wait times and average new patient caseloads have increased, while the number of geneticists has not.

Changes in interpretation of complex clinical genomic test results are inevitable. Ultimately, the ordering health-care provider, clinical geneticist, clinical laboratory, referring specialty and primary care physician, patient, and family each may have a role regarding re-contact. These expectations should be explicitly delineated as part of the informed consent process before the sample is obtained and reviewed again when disclosing initial results.

The evolution of digital health is entwined with federal regulation and policy. Whether considering what is or is not a medical device, the reimbursement for digital medical technologies, or physician services under Medicare or Medicaid related to remote patient monitoring or telehealth, the rules and policies governing digital health have not been easy to distinguish. In the face of rapid innovation, it has been difficult to fit these products and services into existing regulations of the Food and Drug Administration and the Centers for Medicare and Medicaid Services, particularly when these frameworks never contemplated what communications technologies can do today. Instead, rules have been misapplied, and in some cases, they have hampered the use of these technologies, depressing the proliferation of associated services. However, regulations have begun to change. We discuss the policy and regulatory changes that have begun to evolve and where they should continue to head.

Purpose of review Demand for clinical genetics and genomics services is increasing. As discussed in this study, the clinical genetics and genomics workforce is small. How to meet the demand with a limited workforce requires innovation. Recent findings Background data regarding the current state of clinical genetic services including volume of services and make-up of the clinical genetics workforce are presented. The study then identifies opportunities to increase access to clinical genetic service providers using new models of service and discusses examples of solutions which have been implemented in some practice settings. Creative uses of technology to increase providers’ efficiency are highlighted. Summary Clinical genetics service providers need to rise to the occasion and lead the transformation of clinical genetic service delivery. Many of the examples of solutions described in the study can be implemented by other providers now. Additionally, the described solutions may serve to inspire genetic providers to create their own new solutions, which should then be shared with the provider community.

Complete Monosomy 21 Confirmed by FISH and Array-CGH Anita S. Kulharya, Vijay S. Tonk, Carolyn Lovell, and David B. Flannery* Department of Pediatrics, Georgia Health Sciences University, Augusta, Georgia Department of Pathology, Georgia Health Sciences University, Augusta, Georgia OncoMetrix, Poplar Health Care, Memphis, Tennessee Department of Pediatrics, Texas Tech University Health Sciences Center Lubbock, Texas

Objective: To report a child with clinically episodic leukoencephalopathy due to two novel mutations in mitochondrial Complex I NDUFV1 gene, who responded to mitochondrial support. Background Rare cases of NDUFV1 mutations have been reported in patients with Leigh9s syndrome, myoclonic epilepsy, and leukoencephalopathy with and without macrocephaly. Design/Methods: Case study. Results: At 8 months, patient developed transient sitting imbalance. At 32 months after a febrile illness, she had frank ataxia. Brain MR at that time showed circumscribed areas of CSF-like signal changes overlying confluent areas of demyelination. Lysosomal and vanishing white matter testing were normal. Serum lactate varied throughout the course. Gait normalized and parents declined further testing. She developed normally until 44 months when rapid neurologic deterioration occurred during a febrile illness resulting in coma, opisthotonus, spastic quadriparesis, and autonomic dysfunction. Repeat MRI showed decreased circumscribed lesions, but increased underlying demyelination extending to the U fibers. CSF showed 2 WBC9s, normal glucose, protein, amino acids, and pyruvate. CSF lactate was 2.4 mmol/l. EEG showed slowing. NCS were normal. Muscle biopsy was not done. Treatment with intense mitochondrial support temporally arrested decline. Cognitive skills returned, and motor skills improved to walking with a walker. Currently, she has mild spasticity, moderate dysmetria and tremor. Cognitive function is at grade level. She has had no relapses over the last 15 months, since starting mitochondrial support. She is normocephalic. Testing revealed normal mitochondrial DNA. Genomic DNA testing for Complex I revealed two novel heterozygous mutations in NDUFV1 gene; c.479G>A resulting in polarity change and c.753_756delCCCC resulting in a stop codon. Each parent carries one of the mutations. Conclusions: NDUFVI mutations of complex I should be considered in the diagnosis of episodic leukoencephalopathies especially as they may be confused with acquired demyelinating disease. Supported by: Dr. Vanderver is supported by the Myelin Disorders Bioregistry Project. Disclosure: Dr. Sekul has nothing to disclose. Dr. Strickland has nothing to disclose. Dr. Flannery has nothing to disclose. Dr. Figueroa has nothing to disclose. Dr. Vanderver has nothing to disclose.

We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.

Purpose: This study examines the presentation of genetic and behavioral causation and prevention in websites that make medical recommendations to lay people for four diseases: heart disease, diabetes, lung lancer, and depression.Methods: A sample of 73 online medical recommendations from major health institutions and information portals were retrieved for content analysis, with a focus on the depiction of gene-environment relationships.Results: The results show a clear preponderance of behavioral causation and recommendations. When genetic information is presented, genetic and environmental factors (including behaviors) are depicted as independent contributors to health outcomes, rather than as interactive.Conclusion: This study suggests that interactive depictions of genes and behavior should be considered when genetics is presented in medical accounts of causation and prevention of common, complex diseases.

Approximately, 20 cases of interstitial deletions of 9q have been reported in the literature spanning the breakpoints from 9q21 to 9q34. Unlike the 9q subtelomeric deletions, the interstitial deletions do not demonstrate a specific recognizable phenotype, although the majority of patients had microcephaly. Lack of precise molecular delineation of the extent of deletions in the published cases makes it difficult to develop an accurate genotype-phenotype correlation. We report on fine mapping of breakpoints using the Affymetrix Human Mapping 500K Array Set in two unrelated female patients with overlapping de novo deletion in 9q. SNP oligonucleotide microarray analysis (SOMA) indicated these to be relatively large deletions with Patient 1 having a 6.47 Mb deletion (>60 genes) spanning 9q32-q33.2 and Patient 2 having a 9.68 Mb deletion (>20 genes) localized to 9q31.1-q33.1. FISH analysis with BAC clones localized to the breakpoints showed discrepant results in Patient 1. Based on the review of previously reported interstitial 9q deletion patients and our patients, the minimal region of overlap (MRO) appears to encompass the 9q32 region and a phenotype characterized by microcephaly, neurological dysfunction and facial dysmorphism can be deduced. Our study shows the investigative nature of the latest array technology and the limitations of this technology in the accurate delineation of breakpoints.

Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we screened patients with PHS and GCPS for GLI3 mutations. The patient group consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We detected 47 pathological mutations (among 60 probands); when these were combined with previously published mutations, two genotype-phenotype correlations were evident. First, GCPS was caused by many types of alterations, including translocations, large deletions, exonic deletions and duplications, small in-frame deletions, and missense, frameshift/nonsense, and splicing mutations. In contrast, PHS was caused only by frameshift/nonsense and splicing mutations. Second, among the frameshift/nonsense mutations, there was a clear genotype-phenotype correlation. Mutations in the first third of the gene (from open reading frame [ORF] nucleotides [nt] 1-1997) caused GCPS, and mutations in the second third of the gene (from ORF nt 1998-3481) caused primarily PHS. Surprisingly, there were 12 mutations in patients with GCPS in the 3' third of the gene (after ORF nt 3481), and no patients with PHS had mutations in this region. These results demonstrate a robust correlation of genotype and phenotype for GLI3 mutations and strongly support the hypothesis that these two allelic disorders have distinct modes of pathogenesis.

Ronald T. Acton, PhD Mary Ahrens, MS Rando Allikmets, PhD Antonis Antoniou, PhD Brad Aouizerat, PhD Daniel Armstrong, PhD Melissa A. Austin, PhD Dianne Bartels, MS Craig Basson, MD, PhD J. Bronwyn Bateman, MD Judith Benkendorf, MS Janice Berliner, MS Barbara A. Bernhardt, MS Susan Berry, MD Sean Blaine, MD Miriam Blitzer, PhD Donna Blumenthal, MS Donald Bowden, PhD Deborah Bowen, PhD Linda A. Bradley, PhD Brigitte Bressac, PhD Murray Brilliant, PhD David G. Brooks, MD, PhD Peter Bross, MD W. Ted Brown, MD, PhD Wylie Burke, MD, PhD Neil Caporaso, MD John Carlquist, PhD Stephen D. Cederbaum, MD Bin Chen, PhD Tim Church, PhD Robert Clarke, MD Gilbert Cote, PhD William J. Craigen, MD, PhD Dana C. Crawford, PhD Julie Culver, MS, CGC Shelly A. Cummings, MS Christopher Cunniff, MD Abhigit Dasgupta, PhD Martin Delatycki, PhD, MBBS C. Dawn Delozier-Blanchet, PhD Cynthia Dolan, MS Nicole Dowling, PhD Deborah Driscoll, MD Raed Dweik, MD Nathan Ellis, PhD Ervin Epstein, Jr, MD Gareth Evans, MD Robert Fallat, MD Jennifer Farmer, MS W. Andrew Faucett, MS Brenda Finucane, MS David Flannery, MD Tatiana M. Foroud, PhD Morris Foster, PhD Kenneth Friedman, PhD Elizabeth Gettig, MS Fred Gilbert, MD James Goldberg, MD Robert Gorlin, DDs Gregory Grabowski, MD John Graham, Jr, MD, SCD Carol Greene, MD Nathalie Guffon, MD Xiuqing Guo, PhD Alan E. Guttmacher, MD Jonathan L. Haines, PhD Heather Hampel, MS Katharine B. Harris, MBA Barbara W. Harrison, MS Terry Hassold, PhD Michael Hayden, MD, PhD Betsy Hirsch, PhD Rochelle Hirschhorn, MD Kurt Hirschhorn, MD Susan Hodge, DSc Timothy Hoff, PhD W. Allen Hogge, MD R. Lynn Holt, MS Elizabeth Hoodfar, MS Timothy D. Howard, PhD R. Rodney Howell, MD H. Eugene Hoyme, MD Fang-Chi Hsu, PhD Louanne Hudgins, MD John Ioannidis, MD Ethylin Wang Jabs, MD Bart Janssen, PhD Michael M. Kaback, MD Jeffrey Kant, MD, PhD Feige Kaplan, PhD Sharon Kardia, PhD Bronya Keats, PhD Margaret Kenna, MS Richard Kerber, MD Bartha Knoppers, LLD Wendy K. Kohlmann, MS Ruth Kornreich, PhD Deborah Krakow, MD Anita Kulharya, PhD Jean Marc Lalouel, MD Anil Lalwani, MD Susan LaRusse, MS Charles Lee, PhD Bonnie LeRoy, MS Na (Michael) Li, PhD Noralane Lindor, MD Nicola Longo, MD, PhD Thomas Louis, PhD Ira M. Lubin, PhD Maurizio Luisetti, MD Cary Mariash, MD James Mascarello, PhD Anne L. Matthews, PhD Joseph McConnell, PhD Gerry McElvaney, MD Margaret McGovern, PhD, MD Joseph D. McInerney, MS, MA Kent D. McKelvey, Jr. MD Michael B. Miller, PhD Robert Millikan, DVM, PhD Braxton Mitchell, PhD Ilana Mittman, MS Kristin Monaghan, PhD Bernice E. Morrow, PhD Hugo Moser, MD Arno Motulsky, MD Robert Moyzis, PhD John Mulvihill, MD Patricia D. Murphy, PhD Michael F. Murray, MD David L. Nelson, PhD Stanley F. Nelson, MD Kristin Niendorf, MS Matthew Nisbet, PhD Sarah Nolin, PhD Hope Northrup, MD Jeffrey R. O’Connell, PhD Suzanne M. O’Neill, MS, PhD Vivian Ota Wang, PhD Katherine Owen, MD Arti Pandya, MD James Pankow, PhD Shivanand Patil, PhD Holly Peay, MS MaryKay Pelias, PhD, JD Gregory Pence, PhD Beth N. Peshkin, MS June Peters, MS Michael Peterson, MD, PhD Susan K. Peterson, PhD, MPH Daniel Pinkel, PhD Antonio Pizzuti, MD, PhD r e v i e w e r