Infertility is defined as the inability to conceive within one year of unprotected intercourse, and the causes are equally distributed between both sexes. Genetics play a crucial role in couple infertility and respective diagnostic testing should follow available guidelines. Appropriate tiered genetic analyses require comprehensive physical examination of both partners in an infertile couple. A wide range of chromosomal and monogenic variants can be the underlying genetic cause of infertility in both women and men. Accurate clinical phenotyping, together with identification of the genetic origin, helps to recommend the proper treatment and to counsel couples on the success rates and potential risks for offspring.

BACKGROUND: Achondroplasia and mandibulofacial dysostosis with microcephaly (MFDM) are rare monogenic, dominant disorders, caused by gain-of-function fibroblast growth factor receptor 3 (FGFR3) gene variants and loss-of-function elongation factor Tu GTP binding domain-containing 2 (EFTUD2) gene variants, respectively. The coexistence of two distinct Mendelian disorders in a single individual is uncommon and challenges the traditional paradigm of a single genetic disorder explaining a patient\'s symptoms, opening new avenues for diagnosis and management.
METHODS: We present a case of a female patient initially diagnosed with achondroplasia due to a maternally inherited pathogenic FGFR3 variant. She was referred to our genetic department due to her unusually small head circumference and short stature, which were both significantly below the expected range for achondroplasia. Additional features included distinctive facial characteristics, significant speech delay, conductive hearing loss, and epilepsy. Given the complexity of her phenotype, she was recruited to the DDD (Deciphering Developmental Disorders) study and the 100,000 Genomes project for further investigation. Subsequent identification of a complex EFTUD2 intragenic rearrangement confirmed an additional diagnosis of mandibulofacial dysostosis with microcephaly (MFDM).
CONCLUSIONS: This report presents the first case of a dual molecular diagnosis of achondroplasia and mandibulofacial dysostosis with microcephaly in the same patient. This case underscores the complexity of genetic diagnoses and the potential for coexistence of multiple genetic syndromes in a single patient. This case expands our understanding of the molecular basis of dual Mendelian disorders and highlights the importance of considering the possibility of dual molecular diagnoses in patients with phenotypic features that are not fully accounted for by their primary diagnosis.

BACKGROUND: Intersex describes a diversity of individuals with variations in sex characteristics (VSC), reflecting underlying differences in reproductive anatomy, hormones, and/or genes and chromosomes. With a shift towards socially-conscious clinical practices, genetic counsellors (GCs) are increasingly needing to provide comprehensive care to individuals with VSC and their families. However, the current quality of training provided to genetic counsellors on intersex health is unclear.
METHODS: Qualitative interviews were conducted between Jan-Feb 2021 with 20 current and graduated students of Canadian GC training programs to assess the quality of GC education on intersex health topics. An agency-based model of VSC health as proposed by Crocetti et al. was used to guide the inductive thematic data analysis.
RESULTS: Results revealed three key themes: limited discussions on psychosocial considerations when caring for intersex individuals, enthusiasm for integrating more intersex training into the curriculum, and personal initiative in ensuring equity and justice in the care of individuals with VSC.
CONCLUSIONS: These findings demonstrate existing knowledge gaps in the GC curriculum, with a need to increase the profession\'s overall awareness on intersex issues. GC training programs have an opportunity to meet the desires of students while promoting person-centered and validating healthcare for the intersex community.

OBJECTIVE: Rapid genome-wide sequencing (rGWS) continues to transform the care provided to infants with genetic conditions in neonatal intensive care units (NICUs). Previous research has demonstrated that rGWS has immense benefits on patient care; however, little is known about non-genetic healthcare providers\' (HCPs) experiences and perspectives of working with rGWS and supporting families through the rGWS testing process in Canadian NICU facilities. To address this gap, we surveyed and conducted semi-structured interviews with non-genetic HCPs of diverse professions from NICUs in British Columbia.
METHODS: An interpretive description approach was used to analyze interview transcripts to identify patterns and variations in non-genetic HCPs\' experiences and perceptions with rGWS.
RESULTS: Participants had varying degrees of exposure to rGWS and levels of comfort with the testing process. Numerous barriers affecting the implementation of rGWS were identified, including low levels of comprehension of rGWS, longer turn-around times than expected, and having to apply for provincial government approval to access testing. Participants desired more education on rGWS, clear guidelines on the use of rGWS in NICUs, and resources for non-genetic HCPs and parents to support implementation.
CONCLUSIONS: The results from this study can inform the development of workflows and educational resources on the use of rGWS in NICUs, helping to ensure that the NICU team is supported to optimize rGWS implementation.

Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme-which is entirely free-includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service.

UNASSIGNED: To map the existing genomic services available for patients with IRDs across Europe.
UNASSIGNED: A survey was conducted to 24 ophthalmic and/or genetic specialists across 19 European countries. The survey was conducted in an interview style via zoom for participants from 17 out of 19 countries. Interviewees were clinical/medical/ophthalmic geneticists, ophthalmologists/retina specialists and internal medicine specialists. The survey focused on referral pathways, genetic counseling, insurance coverage, awareness of genetic testing and counseling for IRDs among practitioners and patients, and preferred testing methodologies.
UNASSIGNED: Genomic services (testing and counselling) for IRDs vary among countries from an awareness, availability and insurance coverage perspective. Affordability could be a barrier for patients in countries without any payment scheme (eg, Poland) and in countries where only a targeted population is covered (eg, Bulgaria). Genetic counseling via qualified genetic counsellors did not exist in many countries. The level of awareness regarding the benefits of genetic testing in IRDs among healthcare professionals (HCPs) and patients was perceived as low in some countries. Panel-based next-generation sequencing (NGS) was the first test of choice for genetic testing in 68% of the studied countries.
UNASSIGNED: There is some disparity in the approach to genetic testing for IRDs across Europe. Greater awareness of genetic testing services is required among the eye care professional community. A revised approach to the provision of genetic testing services such as centralized free genetic testing with associated interpretation and genetic counselling may help in ensuring equitable access and reimbursement, which will empower patients through improved access to clinical trials, expedite innovation, improve access to therapy and the delivery of care.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson\'s disease; however, individuals with Parkinson\'s disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson\'s disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson\'s disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson\'s disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more \'high risk factors\' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson\'s disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson\'s disease.

Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced life expectancy of patients due to improved treatment and care strategies and the development of more precise and affordable molecular diagnostic tools have prompted a rise in demand of prenatal diagnosis procedures for at-risk couples, including Preimplantation Genetic Testing (PGT). However, challenges remain: heterogeneity among screening programmes, nuances of variant interpretation and availability of novel treatments demand a considerate and knowledgeable approach to genetic counselling. In this work, we retrospectively evaluated the molecular data of 92 unselected couples who received a diagnosis of CFTR-related status and were referred to the genetics clinic at the University Hospital of Padua for genetic counselling on eligibility for PGT. A total of 50 couples were considered eligible for the procedure based on risk of transmitting biallelic pathogenic variants. We report and discuss our experience with this case series in the context of the Italian medical care system and present an overview of the most relevant issues regarding genetic counselling for PGT in CFTR-related disorders.

Outpatient diagnostics for adult patients with intellectual disabilities and developmental disorders were significantly improved when \'Medical Centers for Adults with Disabilities\' (MZEB) were established in 2015 in accordance with a new law (§ 119c SGB V). Due to the multi-professional nature of these MZEBs, cooperation with various specialized centers can be initiated. Accordingly, in 2023, a cooperation between the MZEB in the LVR-Clinic Bedburg-Hau and the Institute of Human Genetics, Heinrich-Heine University (HHU) Düsseldorf was initiated. Interdisciplinary consultation hours for adult patients have been established in Bedburg-Hau offering genetic counselling and testing to identify the underlying genetic entity. We will introduce this new structure and report preliminary results.

The genetic counsellor profession has not yet been established in the German-speaking countries. In 2019 the Medical University of Innsbruck inaugurated the first German-taught Master\'s degree programme in Genetic and Genomic Counselling. In order to discuss prospects and challenges of the genetic counsellor profession in Germany, Austria and Switzerland (DACH region), the MSc programme team organized a two-day workshop with international speakers and medical geneticists from the DACH region. Day 1 was dedicated to the history, training and international profile of the genetic counsellor profession. Day 2 focused on four specific topics: (i) professional role, (ii) acceptance and job title, (iii) formal requirements and (iv) remuneration concepts for genetic counsellors in the DACH region. The workshop showed that the key factor for the successful implementation of the genetic counsellor profession is acceptance and trust within the medical genetics team. Genetic counsellors complement patient care in aspects that might be underserved considering the increasing demand of counselling in genomic medicine. Successful establishment of the genetic counsellor profession will entail the development of interprofessional teams under medical supervision and in the team of medical geneticists.