Preimplantation genetic testing (PGT) has become an integral component of assisted reproductive technology (ART), offering couples the opportunity to screen embryos for genetic abnormalities before implantation during in vitro fertilization (IVF). This comprehensive review explores the advancements and applications of PGT in IVF, covering its various types, technological developments, clinical applications, efficacy, challenges, regulatory aspects, and future directions. The evolution of PGT techniques, including next-generation sequencing (NGS) and comparative genomic hybridization (CGH), has significantly enhanced the accuracy and reliability of genetic testing in embryos. PGT holds profound implications for the future of ART by improving IVF success rates, reducing the incidence of genetic disorders, and mitigating the emotional and financial burdens associated with failed pregnancies and genetic diseases. Recommendations for clinicians, researchers, and policymakers include staying updated on the latest PGT techniques and guidelines, exploring innovative technologies, establishing clear regulatory frameworks, and fostering collaboration to maximize the potential benefits of PGT in assisted reproduction. Overall, this review provides valuable insights into the current state of PGT and its implications for the field of reproductive medicine.

Cystic fibrosis (CF) is a multiorgan disease, caused by autosomal recessive (AR) mutations in the cystic fibrosis transmembrane regulator (CFTR) acting primarily as a chloride channel. CF is most commonly diagnosed in Caucasian populations. Common clinical presentations in pediatric patients include chronic cough, respiratory tract infections such as pneumonia, digestive symptoms, and stunted growth, and malnutrition due to gastrointestinal malabsorption and pancreatic insufficiency. Excessive sweat sodium chloride losses due to dysfunctional sweat glands in CFTR result in volume contraction and secondary hyperaldosteronism leading to renal potassium losses and metabolic alkalosis. Hypokalemic hypochloremic metabolic alkalosis is a known but uncommon presenting sign of the disease, documented as pseudo Bartter syndrome. Common mutations in the CFTR gene are now included in prenatal genetic screening programs. We describe the case of an infant of African descent with normal prenatal screening who presented with severe hypokalemic hypochloremic metabolic alkalosis and was diagnosed with CF with further genetic confirmation of the diagnosis.

Hearing loss is one of the most common sensory disorders in humans. The purpose of this review is to summarize the history and current status of newborn hearing screening in China and to investigate future developmental trends in newborn hearing screening with the intention of sharing experiences and providing a reference for other populations. In the 1980s, the research on hearing monitoring for high-risk infants led to the gradual development of newborn hearing screening in China. With the continuous improvement of screening technology, the newborn hearing screening program was gradually extended to the whole country and became a government-led multidisciplinary public health program. Genetic screening for deafness has been incorporated into newborn hearing screening in many regions of China to help screen for potential and late-onset deafness in newborns. In the future, it is necessary to further establish and improve whole life-cycle hearing screening and healthcare, conduct screening for congenital cytomegalovirus infection, and create a full-coverage, whole life course hearing screening and intervention system. Screening for deafness in China has been marked by 40 years of achievements, which have been a source of pride for entrepreneurs and comfort for patients and their families. Managing hearing screening data information more efficiently and establishing a quality control index system throughout the whole screening process are of paramount importance. The genetic screening for concurrent newborn hearing and deafness has a great clinical importance for the management of congenital deafness and prevention of ototoxicity. A hearing screening and intervention system across the whole life course should be developed.

Sperm and oocytes are building blocks in assisted reproduction. Sperm and ovum donation permit separation of the biological act of producing a child from the psychological process of nurturing and raising the child. However, the art of obtaining and use of these gametes are fraught with ethical and legal challenges. Relevant aspects concerning anonymity, genetic screening, consanguinity, informed consent and risk disclosure, compensation for donors, and child welfare are discussed. Though the issue of anonymity remains controversial, the importance of the welfare of the offspring has come to the fore as a result of the debate. Calls for more rigorous genetic testing for donated gametes to avoid genetic disease transmission, though supported by the principle of beneficence, has to be balanced by its possible deleterious effects on the donors and their relatives especially if findings reveal a serious genetic risk that has no medical treatment as yet. Reimbursement for direct and indirect costs, as well as fair compensation for time lost, inconveniences and risks suffered during treatment is recommended for oocyte donors. The risk of consanguinity remains a problem across the world even though the different guidelines limiting the number of pregnancies by a single gamete may be helpful, if enforceable. It is important that egg donors be clearly made to understand in simple language during the informed consent process of the yet unknown health risks involved so that the consent can be truly voluntary. This will protect donors from the backlash of the doctrine of \"Volenti Non Fit Injuria\". It is also suggested that specific legislation with regards to gamete donation, parenthood, and ART should be passed in countries where these are absent, to avoid controversies that may arise due to current gaps in the law.

Axenfeld-Rieger Syndrome (ARS) is comprised of a group of autosomal dominant disorders that are each characterized by anterior segment abnormalities of the eye. Mutations in the transcription factors FOXC1 or PITX2 are the most well-studied genetic manifestations of this syndrome. Due to the rarity this syndrome, ARS-associated neurological manifestations have not been well characterized. The purpose of this systematic review is to characterize and describe ARS neurologic manifestations that affect the cerebral vasculature and their early and late sequelae. PRISMA guidelines were followed; studies meeting inclusion criteria were analyzed for study design, evidence level, number of patients, patient age, whether the patients were related, genotype, ocular findings, and nervous system findings, specifically neurostructural and neurovascular manifestations. 63 studies met inclusion criteria, 60 (95%) were case studies or case series. The FOXC1 gene was most commonly found, followed by COL4A1, then PITX2. The most commonly described structural neurological findings were white matter abnormalities in 26 (41.3%) of studies, followed by Dandy-Walker Complex 12 (19%), and agenesis of the corpus callosum 11 (17%). Neurovascular findings were examined in 6 (9%) of studies, identifying stroke, cerebral small vessel disease (CSVD), tortuosity/dolichoectasia of arteries, among others, with no mention of moyamoya. This is the first systematic review investigating the genetic, neurological, and neurovascular associations with ARS. Structural neurological manifestations were common, yet often benign, perhaps limiting the utility of MRI screening. Neurovascular abnormalities, specifically stroke and CSVD, were identified in this population. Stroke risk was present in the presence and absence of cardiac comorbidities. These findings suggest a relationship between ARS and neurovascular findings; however, larger scale studies are necessary inform therapeutic decisions.

The South African genetic screening services for breast cancer comprise targeted and comprehensive tests that screen for the presence of genetic alterations. Clinically, these variants determine the risk of disease development as well as treatment approaches best suited for carriers. The current targeted tests screen for seven pathogenic sequence variants, which are mainly common among Whites, a population that constitutes 9.1% of South Africa. However, these tests are offered to all patients despite consistent negative results observed among Blacks, Indians, and Mixed ancestry (known as Coloreds in South Africa). Consequently, Blacks, White, and Colored patients who potentially carry other variants receive unbefitting treatment, resulting in poor clinical response, recurrence, and high mortality. This review aimed to identify the presence and incidence of pathogenic variants in BRCA1/2 previously reported in all South African populations. We selected literature using a scoping review approach, from which we included eight articles and two reports. Overall, we identified 59 BRCA1 and 60 BRCA2 pathogenic sequence variants from a cohort of 5709 patients and unknown patients from 90 families. The most reported variant was BRCA2 c.7943delG, which was common in White and Colored patients. None of the seven common variants was reported in either Blacks or Indians, which demonstrates the urgency to tailor genetic tests which are optimal for all South African patients and present a range of variants which could serve as diagnostic targets for Black, Indian, and Colored patients.

Malignant hyperthermia is a rare but life-threatening pharmacogenetic disorder triggered by exposure to specific anesthetic agents. Although this occurrence could affect virtually any patient during the perioperative time, the pediatric population is particularly vulnerable, and it has a five-fold higher incidence in children compared to adults. In the last few decades, synergistic efforts among leading anesthesiology, pediatrics, and neurology associations have produced new evidence concerning the diagnostic pathway, avoiding unnecessary testing and limiting false diagnoses. However, a personalized approach and an effective prevention policy focused on clearly recognizing the high-risk population, defining perioperative trigger-free hospitalization, and rapid activation of supportive therapy should be improved. Based on epidemiological data, many national scientific societies have produced consistent guidelines, but many misconceptions are common among physicians and healthcare workers. This review shall consider all these aspects and summarize the most recent updates.

Geographical ancestry has been associated with an increased risk of various genetic conditions. Race and ethnicity often have been used as proxies for geographical ancestry. Despite numerous problems associated with the crude reliance on race and ethnicity as proxies for geographical ancestry, some genetic testing in the clinical, research, and employment settings has been and continues to be race- or ethnicity-based. Race-based or race-targeted genetic testing refers to genetic testing offered only or primarily to people of particular racial or ethnic groups because of presumed differences among groups. One current example is APOL1 testing of Black kidney donors. Race-based genetic testing raises numerous ethical and policy questions. Given the ongoing reliance on the Black race in genetic testing, it is important to understand the views of people who identify as Black or are identified as Black (including African American, Afro-Caribbean, and Hispanic Black) regarding race-based genetic testing that targets Black people because of their race. We conducted a systematic review of studies and reports of stakeholder-engaged projects that examined how people who identify as or are identified as Black perceive genetic testing that specifically presumes genetic differences exist among racial groups or uses race as a surrogate for ancestral genetic variation and targets Black people. Our review identified 14 studies that explicitly studied this question and another 13 that implicitly or tacitly studied this matter. We found four main factors that contribute to a positive attitude toward race-targeted genetic testing (facilitators) and eight main factors that are associated with concerns regarding race-targeted genetic testing (barriers). This review fills an important gap. These findings should inform future genetic research and the policies and practices developed in clinical, research, public health, or other settings regarding genetic testing.

BACKGROUND: Although male breast cancer (MBC) is a rare disease, accounting for <1% of all breast cancers, it has significant oncological, survival and psychosocial implications for patients. The aim of this study is to assess the latest literature in the diagnosis, management, oncological outcomes, and psychosocial impact of MBC.
METHODS: A systematic literature review was conducted using the PRISMA guidelines (Moher et al., 2009) [1] to explore the management of MBC, with particular focus on investigative imaging, surgical management, oncological outcomes, survival, genetic screening and psychosocial effects. Electronic databases were searched for randomised control trials, cohort studies and case series involving more than 10 patients. Imaging and surgical techniques, local and distant disease recurrence, survival, genetic screening and psychosocial implications in the setting of MBC were assessed.
RESULTS: The search criteria identified 199 articles, of which 59 met the inclusion criteria. This included 39,529 patients, with a mean age of 64.5 years (55-71), and a mean follow-up of 66.3 months (26.2-115). Mastectomy remains the most frequently used surgical technique, with an average of 89.6%. Loco-regional and distant recurrence rate was 10.1% and 21.4% respectively. Disease-free survival (DFS) at 5 and 10 years was 66.8% and 54.5% respectively. Disease-specific survival (DSS) at 5 and 10 years was 87.1% and 67.1% respectively. Overall survival (OS) at 5 and 10 years was 72.7% and 50.7% respectively. Genetic screening was conducted in 38.6% of patients of which 4.8% and 15.8% were found to be BRCA1 and BRCA2 carriers respectively. Psychosocial studies were conducted mainly using questionnaire and interview-based methodology focusing primarily on awareness of breast cancer in men, support available and impact on gender identity.
CONCLUSIONS: This review demonstrates that men present with later stage disease with subsequent impact on survival outcomes. There remains a paucity of high-level evidence and prospective studies are required. There is a need for increasing awareness amongst the public and health care professionals in order to improve outcomes and reduce stigma associated with MBC.

Understanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic review sought to assess the methodological quality among such studies and examined opportunities for improvement.
We searched PubMed, Cochrane, Embase, and Web of Science for economic evaluations of genetic screening/testing (2013-2019). Methodological rigor and adherence to best practices were systematically assessed using the British Medical Journal checklist.
Across the 47 identified studies, there were substantial variations in modeling approaches, reporting detail, and sophistication. Models ranged from simple decision trees to individual-level microsimulations that compared between 2 and >20 alternative interventions. Many studies failed to report sufficient detail to enable replication or did not justify modeling assumptions, especially for costing methods and utility values. Meta-analyses, systematic reviews, or calibration were rarely used to derive parameter estimates. Nearly all studies conducted some sensitivity analysis, and more sophisticated studies implemented probabilistic sensitivity/uncertainty analysis, threshold analysis, and value of information analysis.
We describe a heterogeneous body of work and present recommendations and exemplar studies across the methodological domains of (1) perspective, scope, and parameter selection; (2) use of uncertainty/sensitivity analyses; and (3) reporting transparency for improvement in the economic evaluation of genetic screening/testing.