Practice Of Medical Genetics Research Articles

Medical students' reproductive health perspectives: Pre- and post-Roe v Wade reversal.

The ability to make informed decisions about reproductive health is a cornerstone principle of the practice of prenatal medical genetics. Unfortunately, these reproductive health decisions have become entangled in the current, contentious political climate. This debate reached an inflection point in 2022 with Dobbs v. Jackson when the Supreme Court of the United States (SCOTUS) overturned the national right to abortion previously established in Roe v. Wade. This decision prompted a reassessment of the opinions of medical students on reproductive health and abortion. Our study focused on a medical school in Alabama, a conservative state that enacted a restrictive abortion ban following the Dobbs ruling. Two surveys, conducted in 2015 and 2022, explored students' viewpoints on reproductive health topics, including abortion. The comparison revealed a significant shift toward more pro-choice perspectives among medical students. Notably, religious affiliation did not consistently align with opinions, as many Christian students supported pro-choice views. Our results suggest that medical students' reproductive health opinions at our institution have shifted to a more pro-choice position over the last decade.

The Study of Human Genomic Diversity in Latin America: Nation and Population

Genomic science values the genetic diversity revealed by advances in genetic sequencing that allow the detailed mapping of diversity at the level of the individual as well as the population group. This has reinforced the idea that humans share the vast majority of their DNA and that the diversity that does exist cannot be parceled into biological categories that align with older categories of race, which are deeply implicated in the practices and structures of racism. However, the practice of genomic science and medical genetics continues to make use of collective categories and populations. This paper argues that practices in genomic science in Latin America change but also reproduce and even reinforce (by biologizing) familiar and enduring categories of race at different levels in society—among scientists and among nonscientists. The Latin American cases are particular in showing that race is often parsed through ideas about the nation, seen as emerging from the mixture of three ancestral populations. Biologization effects can reinforce the racism (and nationalism) that depend on racialized categories. The paper ends by arguing that these effects are a result of the basic concept of population that has in the past organized and continues today to organize genetic diversity in science practice, despite the ability of genomic technologies to handle genetic diversity at the level of the individual. The grounding role of the population concept is accentuated by Latin American national identities being based on ideas of mixture, which entails a corresponding idea of original purities.

Personal journeys to and in human genetics and dysmorphology.

Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.

Genetic characteristic analysis of slight-to-moderate sensorineural hearing loss in children

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.

Ethical considerations in prenatal diagnosis and genetic counseling

Introduction: Prenatal diagnosis, the most widely used reproductive option in the world, refers to methods used to study the health of the fetus. One of the objectives is to detect congenital malformations during fetal development and allow for pregnancy termination. An ethical approach, based on respect for individuals and confidentiality, while avoiding harm and respecting autonomy, are the keys to optimal genetic counseling. Objective: To present some ethical considerations regarding medical genetics as a healthcare practice. To this end, discussion will be based on the fundamental principles of bioethics related to prenatal diagnosis and the genetic counseling process. Results: Ethical considerations in medical genetics are a relatively new topic influenced by the advancement of bioethics and the resolution of ethical and social dilemmas in medical practice. Conclusions: In the field of prenatal diagnosis, ethical, social, and legal conflicts that require careful resolution may arise. Physicians must adhere to bioethical principles such as autonomy, justice, beneficence, and non-maleficence in their professional practice. These principles serve as fundamental norms for their conduct, providing a foundation for reasoning and guiding actions in the genetic counseling process. Keywords: medical ethics; bioethics; prenatal diagnosis; genetic counseling

The potential impact of implementation of expanded carrier screening on pediatric patient diagnoses: A retrospective chart review of patients who receive care in an outpatient genetics clinic in the northeast.

The use of expanded carrier screening (ECS) to assess reproductive risk for autosomal recessive (AR) or X-linked recessive (XLR) conditions has been increasingly integrated into obstetrical care. The aim of this study was to determine what proportion of pediatric patients seen by a medical genetics practice could have had their diagnosis predicted if the parent(s) had undergone currently available ECS at the time of data collection in 2021. A retrospective chart review of patients seen for a medical genetic evaluation at a large academic institution was performed from June 1, 2017, through June 1, 2020. At this institution, 8% of patients were diagnosed with an AR or XLR condition. Of these patients, 61% of the diagnoses could have been predicted in advance if the parent(s) had undergone ECS via the panel referenced in this study. The results of this study highlight the broad range of conditions currently seen in a clinical setting that could be identified as a risk prior to or during pregnancy via ECS. In the prenatal setting, ascertainment of reproductive risk via ECS enables prospective parents to undertake interventions such as prenatal and preimplantation genetic diagnosis. For parents who decline reproductive risk-reducing measures, knowledge about neonatal risk allows for prompt confirmatory testing. In the pediatric setting, the option of early and focused testing can benefit affected individuals and their families.

Service provision of genetics health care in Portugal.

In recent decades, genetics has undergone important technological advances. The rapid shift to genomics has made a strong impact on health systems around the world. In Portugal, this huge increase in consultations and typologies of genetic tests has joined the serious limitations of the few existing genetics services. The following study aims to characterize the current state of the network of genetics services in Portugal regarding its functioning, main challenges, and opportunities.Five semi-structured interviews were conducted, corresponding to 83.33% of the directors of the public genetics services of the National Health Service.Four thematic categories emerged from the analysis: (1) specialty and technical developments, (2) structural difficulties, (3) potentialities, and (4) future directions. The developments are due to the emergence of more comprehensive geneticapplications, specific protocols and patient referral standards, and accreditation of services. The main difficulties encountered in the functioning of the services were difficulty in obtaining funding, lack of human resources, service overload, and lack of exclusive time for training and research. The potentialities mentioned were the establishment of multidisciplinary teams and the best articulation with specialists from other areas. Among the various future directions pointed out, better management of patients' waiting lists, the importance of research, the simplification of test request procedures, and the creation of specialized units inside the genetic services,were reported.The results showed several gaps in the practice of medical genetics that should be addressed with the development of public policies for the recognition and restructuring of medical genetics in health care.

Prenatal Genetic Testing in the Era of Next Generation Sequencing: A One-Center Canadian Experience.

The introduction of next generation sequencing (NGS) technologies has revolutionized the practice of Medical Genetics, and despite initial reticence in its application to prenatal genetics (PG), it is becoming gradually routine, subject to availability. Guidance for the clinical implementation of NGS in PG, in particular whole exome sequencing (ES), has been provided by several professional societies with multiple clinical studies quoting a wide range of testing yields. ES was introduced in our tertiary care center in 2017; however, its use in relation to prenatally assessed cases has been limited to the postnatal period. In this study, we review our approach to prenatal testing including the use of microarray (CMA), and NGS technology (gene panels, ES) over a period of three years. The overall diagnostic yield was 30.4%, with 43.2% of those diagnoses being obtained through CMA, and the majority by using NGS technology (42% through gene panels and 16.6% by ES testing, respectively). Of these, 43.4% of the diagnoses were obtained during ongoing pregnancies. Seventy percent of the abnormal pregnancies tested went undiagnosed. We are providing a contemporary, one tertiary care center retrospective view of a real-life PG practice in the context of an evolving use of NGS within a Canadian public health care system that may apply to many similar jurisdictions around the world.

Clinical Effectiveness of Telemedicine-Based Pediatric Genetics Care.

Telemedicine may increase access to medical genetics care. However, in the pediatric setting, how telemedicine may affect the diagnostic rate is unknown, partially because of the perceived importance of the dysmorphology physical examination. We studied the clinical effectiveness of telemedicine for patients with suspected or confirmed genetic conditions. We conducted a retrospective cohort study of outpatient encounters before and after the widespread implementation of telemedicine (N = 5854). Visit types, diagnoses, patient demographic characteristics, and laboratory data were acquired from the electronic health record. Patient satisfaction was assessed through survey responses. New molecular diagnosis was the primary end point. Patients seen by telemedicine were more likely to report non-Hispanic White ancestry, prefer to speak English, live in zip codes with higher median incomes, and have commercial insurance (all P < .01). Genetic testing was recommended for more patients evaluated by telemedicine than in person (79.5% vs 70.9%; P < .001). Patients seen in person were more likely to have a sample collected, resulting in similar test completion rates (telemedicine, 51.2%; in person, 55.1%; P = .09). There was no significant difference in molecular diagnosis rate between visit modalities (telemedicine, 13.8%; in person, 12.4%; P = .40). Telemedicine and traditional in-person evaluation resulted in similar molecular diagnosis rates. However, improved methodologies for remote sample collection may be required. This study reveals the feasibility of telemedicine in a large academic medical genetics practice and is applicable to other pediatric specialties with perceived importance of physical examination.

Genomics in Egypt: Current Status and Future Aspects.

Egypt is the third most densely inhabited African country. Due to the economic burden and healthcare costs of overpopulation, genomic and genetic testing is a huge challenge. However, in the era of precision medicine, Egypt is taking a shift in approach from “one-size-fits all” to more personalized healthcare via advancing the practice of medical genetics and genomics across the country. This shift necessitates concrete knowledge of the Egyptian genome and related diseases to direct effective preventive, diagnostic and counseling services of prevalent genetic diseases in Egypt. Understanding disease molecular mechanisms will enhance the capacity for personalized interventions. From this perspective, we highlight research efforts and available services for rare genetic diseases, communicable diseases including the coronavirus 2019 disease (COVID19), and cancer. The current state of genetic services in Egypt including availability and access to genetic services is described. Drivers for applying genomics in Egypt are illustrated with a SWOT analysis of the current genetic/genomic services. Barriers to genetic service development in Egypt, whether economic, geographic, cultural or educational are discussed as well. The sensitive topic of communicating genomic results and its ethical considerations is also tackled. To understand disease pathogenesis, much can be gained through the advancement and integration of genomic technologies via clinical applications and research efforts in Egypt. Three main pillars of multidisciplinary collaboration for advancing genomics in Egypt are envisaged: resources, infrastructure and training. Finally, we highlight the recent national plan to establish a genome center that will aim to prepare a map of the Egyptian human genome to discover and accurately determine the genetic characteristics of various diseases. The Reference Genome Project for Egyptians and Ancient Egyptians will initialize a new genomics era in Egypt. We propose a multidisciplinary governance system in Egypt to support genomic medicine research efforts and integrate into the healthcare system whilst ensuring ethical conduct of data.

P050 Consensus based practice guidelines for the management and treatment of Juvenile familial Mediterranean fever: the Egyptian College of Paediatric Rheumatology initiative

Abstract Background Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease, with the highest prevalence amongst Mediterranean countries including Egypt (where there is high carrier rate of MEFV gene), characterized by recurrent attacks of fever and polyserositis. Mutations in the MEFV gene encoding pyrin has been associated with the disease, which causes exaggeration of the inflammatory response through uncontrolled interleukin production. Issuing updated treatment recommendations are vital for the treating healthcare professionals to get well acquainted with its diagnosis &amp; treatment. To produce consensus-based recommendations to guide the early diagnosis, management and follow-up of patients with FMF. Methods The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by the core team. A qualitative synthesis of scientific evidence based on systematic review and clinical experience was conducted to compile evidence for the diagnosis and management of FMF. A consensus process was conducted among the expert panel to generate the final recommendations and grade their strength. 3 rounds of Delphi process were carried out. Results Following 3 Delphi rounds, recommendations were developed for: early diagnosis, who to treat, treatment targets, genetic testing and its interpretation in association with clinical presentation, treatment of FMF and dealing with acute attacks, monitoring of management, identify treatment response, systemic affection, persistent attacks or inflammation, resistant cases, protracted symptoms, as well as remission status. Algorithm for patients’ diagnosis and management is provided. The final document comprises 12 recommendations, each presented with its degree of agreement (0–10), Level of agreement, grade of recommendation and rationale. The degree of agreement was &amp;gt;7/10 in all instances. Conclusion This guideline provides comprehensive approach to the accurate diagnosis and effective management/monitoring of FMF. It also represents a model for the incorporation of medical genetics practice into the more traditional domains of general medicine.

A review on the status quo and implementation methods of ethics education in standardized training for resident doctors in medical genetics department

Clinical practice of Medical Genetics involves application of various genetic techniques for the diagnosis of genetic disorders and subsequent genetic counseling and treatment. The principles of Medical Ethics must be fully taken into account when applying genetic knowledge for medical practice. Medical Ethics education is therefore essential for the standardized training of resident doctors in medical genetics department. With a basic system of Medical Genetics Physician Training established, our hospital has made a preliminary exploration for the development of Medical Ethics teaching in resident training through various teaching practices including seminar, network teaching, case study, scene teaching and outpatient teaching, with an aim to strengthen Medical Ethnics knowledge, professionalism and communication skills, and implement Medical Ethics principles throughout clinical practice.

A review of consensus statements, practice resources, standards and guidelines for clinical applications of next-generation sequencing technologies in the United States

The use of whole exome sequencing (WES) for the detection of disease-causing variants of genetic diseases and for non-invasive prenatal screening (NIPS) of fetal aneuploidies are two major clinical applications of next generation sequencing (NGS). This article has summarized the official documents developed and updated by the American College of Medical Genetics and Genomics (ACMG) on governing WES and NIPS. These include the development of expert consensus policies and position statements on an ongoing basis to guide clinical application of NGS technology and variant analysis, establish evidence-based practical resources, as well as standards and guidelines to govern diagnosis and screening. These ACMG documents are valuable references to Chinese geneticists, but direct adoption of these standards and guidelines may not be practical due to the differences in disease-associated variant frequencies in Chinese population, socioeconomic status, and medical practice between the two countries. It is hoped that this review could facilitate the development of NGS and NIPS standards and guidelines that are consistent with international standards and concordant with medical genetics practice in China to provide high-quality, efficient and safe clinical services for patients and their families with genetic diseases.

Does the law require reinterpretation and return of revised genomic results?

Does the law require reinterpretation and return of revised genomic results?

Addendum: Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities

Laboratory evaluation of patients with developmental delay/intellectual disability, congenital anomalies, and dysmorphic features has changed significantly in the last several years with the introduction of microarray technologies. Using these techniques, a patient's genome can be examined for gains or losses of genetic material too small to be detected by standard G-banded chromosome studies. This increased resolution of microarray technology over conventional cytogenetic analysis allows for identification of chromosomal imbalances with greater precision, accuracy, and technical sensitivity. A variety of array-based platforms are now available for use in clinical practice, and utilization strategies are evolving. Thus, a review of the utility and limitations of these techniques and recommendations regarding present and future application in the clinical setting are presented in this study.

Genomic Diagnosis for Pediatric Disorders: Revolution and Evolution.

Powerful, recent advances in technologies to analyze the genome have had a profound impact on the practice of medical genetics, both in the laboratory and in the clinic. Increasing utilization of genome-wide testing such as chromosomal microarray analysis and exome sequencing have lead a shift toward a “genotype-first” approach. Numerous techniques are now available to diagnose a particular syndrome or phenotype, and while traditional techniques remain efficient tools in certain situations, higher-throughput technologies have become the de facto laboratory tool for diagnosis of most conditions. However, selecting the right assay or technology is challenging, and the wrong choice may lead to prolonged time to diagnosis, or even a missed diagnosis. In this review, we will discuss current core technologies for the diagnosis of classic genetic disorders to shed light on the benefits and disadvantages of these strategies, including diagnostic efficiency, variant interpretation, and secondary findings. Finally, we review upcoming technologies posed to impart further changes in the field of genetic diagnostics as we move toward “genome-first” practice.

Access to reproductive options after prenatal diagnosis—patient access and physician responsibilities: an updated position statement of the American College of Medical Genetics and Genomics (ACMG)

The American College of Medical Genetics and Genomics (ACMG) is concerned with the enactment of laws in some states that prevent or restrict access to termination of pregnancy after prenatal diagnosis of genetic disorders or congenital anomalies. The practice of medical genetics is predicated on the principle of providing patients with complete and accurate information on the condition that affects them, a member of their family, or an unborn fetus, and then discussing the management options that are available. The ACMG believes strongly that a balanced discussion of reproductive options is required. In some cases, patients will elect to alter the course of their pregnancy or pregnancy care. Patients may decide to investigate adoption or choose to learn about the expected outcome, neonatal care, and long-term care of a child with disabilities. They may also choose termination of pregnancy. Pregnancy termination should be available to pregnant women when their fetus has been diagnosed with a genetic disorder or congenital anomaly. Ideally, this is considered after discussions between the patient’s healthcare provider(s) and the pregnant woman or couple with the goal of facilitating their choice of a safe and acceptable management plan. Access to safe and legal termination of pregnancy for genetic disorders or congenital anomalies that are diagnosed prenatally is an important option for some patients, and the ACMG strongly opposes any legislation that places limits on this access. Further, it is the legal and ethical responsibility of health-care professionals to provide complete and accurate information including all management options to patients. Laws that criminalize healthcare professionals for informing patients of their options, including termination of pregnancy, are contrary to the sanctity of the doctor–patient relationship and principles of autonomy. Accordingly, ACMG strongly opposes any legislation that prohibits healthcare professionals from providing complete and accurate medical care, or in any manner penalizes the provision of such 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. This statement is designed primarily as an educational resource for medical geneticists and other clinicians to help them provide quality medical services. Adherence to this statement is completely voluntary and does not necessarily assure a successful medical outcome. This statement should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinician should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this statement. Clinicians also are advised to take notice of the date this statement was adopted, and to consider other medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures. The Board of Directors of the American College of Medical Genetics and Genomics approved this statement on 20 April 2018.

Current conditions in medical genetics practice

PurposeThis 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. MethodsUsing 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. ResultsThe 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. ConclusionWhen 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.

SU46 - PSYCHIATRIC GENETIC COUNSELING: CHALLENGES IN AUTISM SPECTRUM DISORDERS

Autism Spectrum Disorders (ASD) have one of the highest estimates of heritability among psychiatric conditions. Genetic testing is now considered standard of care for diagnosis of ASD etiology, and is increasingly available, affordable, and offered to patients and their families. The 2013 American College of Medical Genetics Practice Guidelines estimates a genetic diagnostic yield of 30–40% in ASD cases, recommending Chromosome Microarray (CMA), single gene testing such as FMR1, as well as other testing such as metabolic studies. As of 2017, more than 20 academic and commercial laboratories have developed clinical genetic tests specific for ASD, which are being marketed as diagnostic testing to clinicians worldwide. However, these gene panels often have low clinical validity, and often include genes where the associations between the loci and ASD are unclear. Little is known regarding the practical experience of individuals with ASD undergoing genetic testing. Here, we present five illustrative cases and suggest standardized approaches for genetic counseling in ASD. Since 2013, clinical genetic testing has been routinely offered to individuals with ASD in our Genetics clinic. The most common test offered was CMA, followed by FMR1 and whole exome sequencing. Through retrospective chart review, five representative cases were selected to highlight the diagnostic and counseling complexities. From 2013 to 2016, we provided genetic counseling to 29 individuals with ASD, resulting in at least a partial genetic diagnosis in 34% of cases, a variant of unknown significance in 10% of cases, and incidental findings in 7% of cases. We present five cases of nonsyndromic ASD with variable genetic testing results (1q21.1 deletion, 16p11.2 duplication, 15q13.3 duplication, AUTS2, 47, XYY) and discuss the genetic counseling issues for each. In our collective experience with these and other cases, we have found that diagnostic challenges include phenotypic and locus heterogeneity, variable expressivity, reduced penetrance, causative versus risk alleles, and changing genetic associations as research progresses. Psychosocial challenges include misleading information online, illness representation beliefs of patients and families, stigma, guilt and shame, and family communication. It is not enough to know that certain genetic factors are associated with ASD. Translating this information in a meaningful way for patients and families is the ultimate goal of all clinically-directed research. The reactions of the families described in this case series illustrate these challenges. We recommend standardizing informed consent for genetic testing in ASD, especially regarding the inherent uncertainties, and to include referral to a clinical genetic specialist if available. Careful and informed genetic counseling is crucial and may lead to improved coping and adaptation, and may reduce negative consequences of stigma and discrimination.

Making pretest genomic counseling optional: lessons from the RAVE study

Making pretest genomic counseling optional: lessons from the RAVE study