Presymptomatic Genetic Testing Research Articles

Predicting age of onset and progression of disease in late-onset genetic neurodegenerative diseases: An ethics review and research agenda.

Currently, a prognostic biomarker-based model is being developed to predict the onset and disease progression of Huntington's Disease (HD) and Spinocerebellar Ataxia (SCA) types 1 and 3, both late-onset genetic neurodegenerative diseases lacking a disease-modifying treatment (DMT). The need for more accurate predictions of onset and disease progression arises in the context of clinical trials evaluating the effectiveness of potential DMTs and identifying the optimal time to initiate such a DMT. Moreover, such a prognostic model may provide mutation carriers with personal utility. The aim of this article is to anticipate the ethical issues raised by these new prognostic models and to formulate the ethical issues that need to be addressed to facilitate an ethically responsible development and implementation of such a model. Part one of this article describes the ethical issues raised by presymptomatic genetic testing for HD and evaluates whether and how these issues may also occur by predicting onset and disease progression. Part two presents the results of a critical interpretative review into the ethical issues raised by biomarker testing in other late-onset neurodegenerative diseases lacking a DMT. The review aims to identify new ethical issues related to biomarker testing for predicting the onset and disease progression of HD and SCA. Finally, based on parts one and two, part three proposes a research agenda for the near future regarding the most pressing ethical issues that need to be addressed to ensure an ethically responsible implementation of such a prognostic model in both research settings and clinical practice.

Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children.

This Position Statement provides guidelines for health professionals who work with individuals and families seeking predictive genetic testing and laboratory staff conducting the tests. It presents the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity, and adults living with reduced or fluctuating cognitive capacity.Predictive Testing Recommendations: (1) Predictive testing in adults, young people and children should only be offered with pretest genetic counseling, and the option of post-test genetic counseling. (2) An individual considering whether to have a predictive test should be supported to make an autonomous and informed decision. Regarding Children and Young People: (1) Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies, or other medical interventions in the immediate future. (2) Where symptoms are likely to develop in childhood, in the absence of direct medical benefit from this knowledge, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. (3) Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make an autonomous and informed decision. This is applicable regardless of whether there is some action that can be taken in adulthood.

Clinically-relevant Germline Variants in Children with Non-Medullary Thyroid Cancer.

The underlying genetic cause of non-medullary thyroid cancer (NMTC) in children is often unknown, hampering both predictive testing of family members and preventive clinical management. Our objectives were to investigated the potential heritability in the largest childhood NMTC cohort that has been genotyped to date. Nationwide retrospective cohort study. Tertiary referral centers. In total, 97 patients diagnosed with pediatric NMTC between 1970-2020 were included in this study. Germline whole genome sequencing (WGS). The main outcome measures were mutation detection yield in 1) clinically-relevant tumor predisposition genes, and 2) genes previously associated with NMTC. In total, 13 of 97 patients (13%) carried a germline (likely) pathogenic (P/LP) variant in a well-known tumor predisposition gene: APC (n=1), BRCA2 (n=2), CHEK2 (n=4), DICER1 (n=4), HOXB13 (n=1), , and MITF (n=1). In addition, one patient was diagnosed with Pendred syndrome (SLC26A4) and nine variants of high interest were found in other NMTC candidate susceptibility genes. The reported prevalence (13%) of germline variants in well-known tumor predisposing genes and the added value of a revised personal-/family history and histology led us to recommend genetic counseling for all childhood NMTC patients.The detected tumor predisposition syndromes are associated with a risk for second cancers which necessitates additional surveillance of the index patients and pre-symptomatic genetic testing of at risk family members.

Randomized Trial of Telegenetic Counseling for Gene Testing in Huntington’s Disease (P1-11.011)

<h3>Objective:</h3> To determine the feasibility and patient satisfaction of telegenetic counseling for Huntington’s Disease (HD). <h3>Background:</h3> Genetic counseling is necessary for pre-symptomatic or symptomatic HD genetic testing, but the lack of access to counseling due to geography or expense is a critical gap for many patients. The hypothesis of this study was that there would be no difference in patient satisfaction between telegenetic counseling (teleGC) or in-person counseling (in-personGC) for HD testing. <h3>Design/Methods:</h3> This was a prospective, randomized, unblinded study of either teleGC or in-personGC for HD gene testing. Participants had standardized genetic counseling from a certified genetic counselor in the clinic or via HIPPA appropriate telemedicine platform first, then crossed over. A study coordinator interviewed the participant using a telehealth survey after each encounter. <h3>Results:</h3> 19 in-personGC and 15 teleGC participants were included: 68% women, 41±15 yrs, 80% white, 10% Hispanic, and +CAG=45±4.4 (n=15) (P&gt;0.1). All participants were satisfied with their initial counseling experience when asked to rate on a scale of 1–10 (median 10/10, p=0.94). The majority of symptomatic HD participants (5/7) preferred in-person GC. The main advantage of teleGC was reduction in travel time for the in-personGC first (n=16) and teleGC first (n=11) groups. Technical challenges were reported (n=11) and the counseling slide deck was difficult to see (n=4) with teleGC. Visually seeing the genetic counselor improved understanding for both in-personGC (n=10) and teleGC (n=8) participants. Participants felt they were able to pick up on emotional cues (n=33) and were comfortable asking questions (n=34). <h3>Conclusions:</h3> Telegenetic counseling is a feasible option for HD gene testing, if patients are able to overcome technical issues. Having a video visit, rather than a phone call, should be considered when using telegenetic counseling for HD gene testing. In-person counseling may be preferred to increase understanding of the material in some patients, such as motor manifest HD. <b>Disclosure:</b> Dr. Hall has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier - Parkinsonism and Related Disorders. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Hall has received research support from Parkinson’s Foundation. The institution of Dr. Hall has received research support from CHDI. The institution of Dr. Hall has received research support from Biohaven. The institution of Dr. Hall has received research support from Neurocrine. The institution of Dr. Hall has received research support from Uniqure. Dr. Hall has received personal compensation in the range of $500-$4,999 for serving as a Study section with NIH. Dr. Rosenbaum has nothing to disclose. Jacob Hawkins has nothing to disclose. Bichum Ouyang has nothing to disclose. Christa Suzanne Cooper, PA has nothing to disclose. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott Laboratories. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie Pharmaceuticals. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva Pharmaceuticals.

A CHANGE OF HEART: A CASE OF CARDIAC AMYLOIDOSIS

A CHANGE OF HEART: A CASE OF CARDIAC AMYLOIDOSIS

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies-A Review.

Simple SummaryA significant progress in understanding the genetic basis of childhood cancers has been made over the past years. Genome sequencing has identified significant differences between paediatric and adult cancers. A higher prevalence of germline alterations in cancer predisposition genes is observed, in comparison to somatic mutations in paediatric cancers. Interestingly, pathogenic germline variants and somatic mutations can affect the same genes. The early recognition of genetic predispositions for childhood cancers may provide an opportunity of therapy adjustment and specific screening for different syndrome-related malignancies. Research on the biological function of gene variants with increased cancer predispositions is critical to the needs of adequate patient management. Genetic counselling with targeted therapy have become basis of integrated cancer care in paediatric oncology.The view of paediatric cancer as a genetic disease arises as genetic research develops. Germline mutations in cancer predisposition genes have been identified in about 10% of children. Paediatric cancers are characterized by heterogeneity in the types of genetic alterations that drive tumourigenesis. Interactions between germline and somatic mutations are a key determinant of cancer development. In 40% of patients, the family history does not predict the presence of inherited cancer predisposition syndromes and many cases go undetected. Paediatricians should be aware of specific symptoms, which highlight the need of evaluation for cancer syndromes. The quickest possible identification of such syndromes is of key importance, due to the possibility of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. Targetable driver mutations and corresponding signalling pathways provide a novel precision medicine strategy.Therefore, there is a need for multi-disciplinary cooperation between a paediatrician, an oncologist, a geneticist, and a psychologist during the surveillance of families with an increased cancer risk. This review aimed to emphasize the role of cancer-predisposition gene diagnostics in the genetic surveillance and medical care in paediatric oncology.

Dilemma of presymptomatic testing in children with history of late onset neurodegenerative spinocerebellar ataxia in Indonesia

Background: Spinocerebellar ataxia (SCA) is a late onset neurodegenerative disorder in which coordination and balance are affected. Although many international guidelines have been established regarding presymptomatic testing, it is still a grey area in Indonesia. We report two large families with advanced stages of SCA who underwent presymptomatic genetic testing in children along counseling process.Case presentation: Thorough examination was performed, including pedigree construction, physical and neurological examination, gene mutation analyses for patients, and presymptomatic testing for family members, including children. SCA3/MJD1 gene mutation analysis was done in both cases, and a full penetrance CAG repeat expansion was found in both affected patients. Two different outcomes were observed in the offspring, who were both children. The risk and consequences of positive results had been explained in a counseling session to family members, who decided to keep the information until the child would have reached legally adult age.Conclusions: In developing countries such as Indonesia, problems arose due to ethical issues, knowledge of genetic diseases, and inaccessible molecular diagnostics. Culture, religion and tribe diversities may create additional challenges. These cases emphasize the need for careful consideration of presymptomatic testing in children, especially in complicated situations where psychological and ethical issues should be addressed.

Clinical and Genetic Evaluation of People with or at Risk of Hereditary ATTR Amyloidosis: An Expert Opinion and Consensus on Best Practice in Ireland and the UK.

Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a consensus statement. This consensus statement provides recommendations for three different groups: (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis.

National survey of presymptomatic genetic testing for adult-onset hereditary neuromuscular diseases-system development for after the establishment of therapies

As therapies for hereditary neuromuscular diseases are developed, the need for presymptomatic genetic testing and genetic counseling for early treatment is expected to increase. In Japan, there is no uniformly recommended protocol for presymptomatic genetic testing. In order to provide basic data for the establishment of a presymptomatic genetic testing system, we surveyed medical genetics departments in Japan about their current status (response rate: 67.4%). The questionnaire survey revealed that approximately 60% of facilities had established their own procedures for presymptomatic genetic testing, but the approaches used varied from facility to facility. The interview survey enabled us to identify the essential factors for the establishment of a presymptomatic genetic testing system for each case, each facility, and at the overall level. In the future, there is a need to develop a standardized protocol to help establish a presymptomatic genetic testing system.

Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases.

Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. While much is still unknown, advances in other neurodegenerative diseases offer valuable insights. Indeed, it is increasingly clear that the well-recognized clinical syndromes of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, spinal muscular atrophy and frontotemporal dementia are also each preceded by a pre-symptomatic or prodromal period of varying duration, during which the underlying disease process unfolds, with associated compensatory changes and loss of inherent system redundancy. Key insights from these diseases highlight opportunities for discovery in amyotrophic lateral sclerosis. The development of biomarkers reflecting amyloid and tau has led to a shift in defining Alzheimer’s disease based on inferred underlying histopathology. Parkinson’s disease is unique among neurodegenerative diseases in the number and diversity of non-genetic biomarkers of pre-symptomatic disease, most notably REM sleep behaviour disorder. Huntington’s disease benefits from an ability to predict the likely timing of clinically manifest disease based on age and CAG-repeat length alongside reliable neuroimaging markers of atrophy. Spinal muscular atrophy clinical trials have highlighted the transformational value of early therapeutic intervention, and studies in frontotemporal dementia illustrate the differential role of biomarkers based on genotype. Similar advances in amyotrophic lateral sclerosis would transform our understanding of key events in pathogenesis, thereby dramatically accelerating progress towards disease prevention. Deciphering the biology of pre-symptomatic amyotrophic lateral sclerosis relies on a clear conceptual framework for defining the earliest stages of disease. Clinically manifest amyotrophic lateral sclerosis may emerge abruptly, especially among those who harbour genetic mutations associated with rapidly progressive amyotrophic lateral sclerosis. However, the disease may also evolve more gradually, revealing a prodromal period of mild motor impairment preceding phenoconversion to clinically manifest disease. Similarly, cognitive and behavioural impairment, when present, may emerge gradually, evolving through a prodromal period of mild cognitive impairment or mild behavioural impairment before progression to amyotrophic lateral sclerosis. Biomarkers are critically important to studying pre-symptomatic amyotrophic lateral sclerosis and essential to efforts to intervene therapeutically before clinically manifest disease emerges. The use of non-genetic biomarkers, however, presents challenges related to counselling, informed consent, communication of results and limited protections afforded by existing legislation. Experiences from pre-symptomatic genetic testing and counselling, and the legal protections against discrimination based on genetic data, may serve as a guide. Building on what we have learned—more broadly from other pre-symptomatic neurodegenerative diseases and specifically from amyotrophic lateral sclerosis gene mutation carriers—we present a road map to early intervention, and perhaps even disease prevention, for all forms of amyotrophic lateral sclerosis.

Genetic counselling as a route to enhanced autonomy: using a sequential mixed methods research approach to develop a theory regarding presymptomatic genetic testing for young adults at risk of inherited cancer syndromes.

Undertaking presymptomatic or predictive genetic testing should involve a considered choice. Decisions regarding genetic testing for young adults have to be considered within the context of their key life stage, which may involve developing a career, forming partnerships and/or becoming parents. The aim of this study was to develop a theoretical model regarding the factors involved when young adults (18-30years) undergo presymptomatic genetic testing for inherited cancer syndromes. The model evolved from synthesis of results of a sequential mixed methods study involving a systematic review, a qualitative study and a quantitative study. The resulting model shows that young adults at risk of inherited cancer syndromes are influenced by others to have testing and come to counselling with their decision already made. However, genetic counselling enhances their feelings of autonomy and integration of their genetic status into their lives. Our theoretical model could be a valid support during the genetic counselling process for young adults and their parents, as it may sensitise professionals to the specific needs of this population, including education and support to autonomous decision-making. Counselling approaches should be modified in this population: an inclusive, multi-step counselling process is needed, with timing and setting set according to the specific features of this sensitive population.

Genetics of Huntington’s disease and special considerations for pre-symptomatic genetic testing

Genetics of Huntington’s disease and special considerations for pre-symptomatic genetic testing

Who and Why? Requests for Presymptomatic Genetic Testing for Amyotrophic Lateral Sclerosis/Frontotemporal Dementia vs Huntington Disease.

ObjectiveWe aimed to describe the population of subjects seeking presymptomatic counseling for amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD) and compared them with those demanding the well-established presymptomatic test for Huntington disease (HD).MethodsWe retrospectively examined the requests of a cohort of individuals at risk of familial ALS/FTD and 1 at risk of HD over the same time frame of 11 years. The individuals were seen in the referral center of our neurogenetics unit.ResultsOf the 106 presymptomatic testing (PT) requests from subjects at risk of ALS/FTD, 65% were seen in the last 3 years. Over two-thirds of the subjects were at risk of carrying mutations responsible for ALS, FTD, or both. Sixty-two percent of the subjects came from families with a known hexanucleotide repeat expansion in C9ORF72. During the same period, we counseled 840 subjects at risk of HD. Subjects at risk of ALS/FTD had the presymptomatic test significantly sooner after being aware of their risk, but were older than those at risk of HD. The youngest subjects requesting the test had the highest disease load in the family (p < 0.05).ConclusionsDemands for PT for ALS/FTD have been increasingly growing, particularly since the discovery of the C9ORF72 gene. The major specificity of the genetic counseling for these diseases is the unpredictability of the clinical phenotype for most of the genes involved. Awareness of this added uncertainty does not prevent individuals from taking the test, as the dropout rate is not higher than that for HD.

Can Genetic Nondiscrimination Laws Save Lives?

Numerous state laws and the federal Genetic Information Nondiscrimination Act (GINA) have been enacted to prevent or redress genetic discrimination in employment and health insurance, but laws protecting against genetic discrimination in life insurance have been less common and weak. Consequently, some individuals with a genetic risk of a serious illness have declined presymptomatic genetic testing, thereby decreasing their prevention and treatment options and increasing their mortality risk. In 2020, Florida became the first state to prohibit life insurance companies from using the results of presymptomatic genetic tests in underwriting. Although the law was "only" intended to prevent genetic discrimination, a possible or even likely consequence of the law will be to encourage timely genetic testing by at-rick individuals and thereby save lives.

Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.

Whole Exome Sequence Analysis Provides Novel Insights into the Genetic Framework of Childhood-Onset Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) describes a rare, progressive vascular disease caused by the obstruction of pulmonary arterioles, typically resulting in right heart failure. Whilst PAH most often manifests in adulthood, paediatric disease is considered to be a distinct entity with increased morbidity and often an unexplained resistance to current therapies. Recent genetic studies have substantially increased our understanding of PAH pathogenesis, providing opportunities for molecular diagnosis and presymptomatic genetic testing in families. However, the genetic architecture of childhood-onset PAH remains relatively poorly characterised. We sought to investigate a previously unsolved paediatric cohort (n = 18) using whole exome sequencing to improve the molecular diagnosis of childhood-onset PAH. Through a targeted investigation of 26 candidate genes, we applied a rigorous variant filtering methodology to enrich for rare, likely pathogenic variants. This analysis led to the detection of novel PAH risk alleles in five genes, including the first identification of a heterozygous ATP13A3 mutation in childhood-onset disease. In addition, we provide the first independent validation of BMP10 and PDGFD as genetic risk factors for PAH. These data provide a molecular diagnosis in 28% of paediatric cases, reflecting the increased genetic burden in childhood-onset disease and highlighting the importance of next-generation sequencing approaches to diagnostic surveillance.

Gene Panel Tumor Testing in Ovarian Cancer Patients Significantly Increases the Yield of Clinically Actionable Germline Variants beyond BRCA1/BRCA2.

Simple SummaryGermline and somatic variant testing of the BRCA1 and BRCA2 genes are important to predict treatment response to PARP inhibitors in ovarian cancer patients. However, germline variants in other genes besides BRCA1 and BRCA2 are associated with ovarian cancer predisposition, which would be missed by a genetic testing aimed only at treatment decision. We aimed to evaluate the yield of clinically actionable germline variants using next-generation sequencing of a customized panel of 10 genes for the analysis of pathology samples of ovarian carcinomas. We identified clinically actionable germline variants in a significantly higher proportion of ovarian cancer patients when compared with genetic testing focused only on BRCA1 and BRCA2. This strategy increases the chance to make available genetic counseling, presymptomatic genetic testing, and gynecological cancer prophylaxis to female relatives who turn out to be healthy carriers of deleterious germline variants. Since the approval of PARP inhibitors for the treatment of high-grade serous ovarian cancer, in addition to cancer risk assessment, BRCA1 and BRCA2 genetic testing also has therapeutic implications (germline and somatic variants) and should be offered to these patients at diagnosis, irrespective of family history. However, variants in other genes besides BRCA1 and BRCA2 are associated with ovarian cancer predisposition, which would be missed by a genetic testing aimed only at indication for PARP inhibitor treatment. In this study, we aimed to evaluate the yield of clinically actionable germline variants using next-generation sequencing of a customized panel of 10 genes for the analysis of formalin-fixed paraffin-embedded samples from 96 ovarian carcinomas, a strategy that allows the detection of both somatic and germline variants in a single test. In addition to 13.7% of deleterious germline BRCA1/BRCA2 carriers, we identified 7.4% additional patients with pathogenic germline variants in other genes predisposing for ovarian cancer, namely RAD51C, RAD51D, and MSH6, representing 35% of all pathogenic germline variants. We conclude that the strategy of reflex gene-panel tumor testing enables the identification of clinically actionable germline variants in a significantly higher proportion of ovarian cancer patients, which may be valuable information in patients with advanced disease that have run out of approved therapeutic options. Furthermore, this approach increases the chance to make available genetic counseling, presymptomatic genetic testing, and gynecological cancer prophylaxis to female relatives who turn out to be healthy carriers of deleterious germline variants.

Actionability and scope should determine the extent of counselling for presymptomatic genetic testing.

Patients considering undergoing presymptomatic genetic and genomic testing commonly receive prior genetic counselling. However, there is a need to discuss further why genetic counselling has such unique and high importance in many countries worldwide. This discussion will help to rationalise resource allocations within healthcare systems and improve patient communication in genetics and other fields.

Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children.

In 2020, the Human Genetics Society of Australasia released its Position Statement on Predictive and Presymptomatic Genetic Testing in Adults and Children. This Position Statement synthesizes the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity and adults living with reduced or fluctuating capacity. Recommendations include that predictive testing in adults, young people and children should only be offered with pretest genetic counseling and the option of posttest genetic counseling. An individual considering (for themselves or on behalf of another) whether to have a predictive test should also be supported to allow them to make an autonomous and informed decision. Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies or other medical interventions in the immediate future. Where symptoms are likely to develop in childhood, in the absence of options to implement surveillance or risk reduction measures, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make their own autonomous and informed decision.

Presymptomatic Genetic Testing and Management of Individuals at Risk

Presymptomatic Genetic Testing and Management of Individuals at Risk