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Objectives New diagnostic criteria for NF2- related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed. Methods The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England's specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for NF2, LZTR1 and SMARCB1 was performed. Results 1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited NF2 pathogenic variant (p<0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of LZTR1- related schwannomatosis and SMARCB1- related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4--18.4 times lower than NF2. Conclusions This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling [ABSTRACT FROM AUTHOR]

Background: There are no established guidelines for the follow up of infants born after a prenatal diagnosis of a genomic copy number variant (CNV), despite their increased risk of developmental issues. The aims of this study were (i) to determine the perinatal outcomes of fetuses diagnosed with and without a CNV, and (ii) to establish a population-based paediatric cohort for long term developmental follow up. Methods: An Australian state-wide research database was screened for pregnant individuals who had a prenatal chromosomal microarray (CMA) between 2013–2019 inclusive. Following linkage to laboratory records and clinical referrer details, hospital records were manually reviewed for study eligibility. Eligible participants were mother–child pairs where the pregnancy resulted in a livebirth, the mother was able to provide informed consent in English (did not require a translator) and the mother was the primary caregiver for the child at hospital discharge after birth. Research invitations were sent by registered post at an average of six years after the prenatal diagnostic test. Statistical analysis was performed in Stata17. Results: Of 1832 prenatal records examined, 1364 (74.5%) mother–child pairs were eligible for recruitment into the follow up cohort. Of the 468 ineligible, 282 (60.3%) had 'no live pregnancy outcome' (209 terminations of pregnancy (TOP) and 73 miscarriages, stillbirths, and infant deaths), 157 (33.5%) required a translator, and 29 (6.2%) were excluded for other reasons. TOP rates varied by the type of fetal CNV detected: 49.3% (109/221) for pathogenic CNVs, 18.2% (58/319) for variants of uncertain significance and 3.3% (42/1292) where no clinically significant CNV was reported on CMA. Almost 77% of invitation letters were successfully delivered (1047/1364), and the subsequent participation rate in the follow up cohort was 19.2% (201/1047). Conclusions: This study provides Australia's first population-based data on perinatal outcomes following prenatal diagnostic testing with CMA. The relatively high rates of pregnancy loss for those with a prenatal diagnosis of a CNV presented a challenge for establishing a paediatric cohort to examine long term outcomes. Recruiting a mother–child cohort via prenatal ascertainment is a complex and resource-intensive process, but an important step in understanding the impact of a CNV diagnosis in pregnancy and beyond. Trial registration: ACTRN12620000446965p; Registered on April 6, 2020. [ABSTRACT FROM AUTHOR]

Objectives: To determine the long‐term control rates and hearing outcomes for growing vestibular schwannoma in NF2‐related schwannomatosis (NF2) treated with stereotactic radiosurgery (SRS) and fractionated radiotherapy (FRT). Methods: Retrospective review of all patients treated with SRS/FRT between 1986 and2021 from a tertiary NF2 unit. Overall tumor control was defined as: (1) growth control (growth failure was defined as growth in any dimension of 3 millimetres or more from baseline post‐SRS/FRT), and (2) treatment control (no need for further intervention). Loss of serviceable hearing was defined as a drop in speech discrimination score below 50% after SRS/FRT. Results: There were 81 cases, with a mean duration of follow‐up of 125 months. Overall control rate was 72% (58/81), with 80% (65/81) growth control and 74% (60/81) treatment control. There was a 5‐year actuarial survival of 77% and 10‐year survival of 71%. Forty‐three percent (30/69) of cases did not have serviceable hearing at baseline. Of those remaining, 49% (19/39) preserved serviceable hearing during follow‐up at a mean of 106 months. Actuarial survival for preservation of serviceable hearing at 5 and 10 years was 69% and 53%. There were poorer outcomes with increasing genetic severity, and with baseline tumor size >3 cm. No cases of SRS/FRT‐related malignancy were identified at a mean follow‐up of 10 years. Conclusion: Stereotactic radiosurgery/fractionated radiotherapy are an effective option to treat growing vestibular schwannoma in patients with NF2 with the potential for hearing preservation in a proportion of patients. Level of Evidence: 4—Case Series Laryngoscope, 134:2364–2371, 2024 [ABSTRACT FROM AUTHOR]

Almost half of infertility cases involve male infertility. Understanding the consequence of a diagnosis of male infertility, as a sole or partial contributor to the couples’ infertility, to the mental health of men is required to ensure clinical care meets their psychological needs. The aim of this systematic analysis was to synthesize the evidence regarding whether men diagnosed with male factor infertility experience greater psychological distress than (1) men described as fertile and (2) men in couples with other infertility diagnoses. Online databases were searched using a combination of Medical Subject Headings (MeSH) headings and keywords relating to male infertility and psychological distress. The search yielded 1016 unique publications, of which 23 were included: 8 case–control, 14 prospective cohort, and 1 data linkage studies. Seven aspects of psychological distress were identified depression, anxiety, self-esteem, quality of life, fertility-related stress, general psychological stress or well-being, and psychiatric conditions. Case–control studies reported that men with male factor infertility have more symptoms of depression, anxiety and general psychological distress, worse quality of some aspects of life, and lower self-esteem than controls. When men with male factor infertility were compared to men in couples with other causes of infertility, there were few differences in the assessed aspects of psychological distress. Despite methodological limitations within the studies, this systematic analysis suggests that the experience of infertility, irrespective of its cause, negatively affects men’s mental health and demonstrates the need for assisted reproduction technology (ART) providers to consider men undergoing assisted reproduction as individuals with their own unique support needs. [ABSTRACT FROM AUTHOR]

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition., Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy. The results obtained from testing at least 1281 genes were provided to the reproductive couples. We aimed to ascertain the psychosocial effects on participants, the acceptability of screening to all participants, and the reproductive choices of persons identified as having an increased chance of having a child with a condition for which we screened., Results: Among 10,038 reproductive couples enrolled in the study, 9107 (90.7%) completed screening, and 175 (1.9%) were newly identified as having an increased chance of having a child with a genetic condition for which we screened. These conditions involved pathogenic variants in 90 different genes; 74.3% of the conditions were autosomal recessive. Three months after receiving the results, 76.6% of the couples with a newly identified increased chance had used or planned to use reproductive interventions to avoid having an affected child. Those newly identified as having an increased chance had greater anxiety than those with a low chance. The median level of decisional regret was low in all result groups, and 98.9% of participants perceived screening to be acceptable., Conclusions: Couple-based reproductive genetic carrier screening was largely acceptable to participants and was used to inform reproductive decision making. The delivery of screening to a diverse and geographically dispersed population was feasible. (Funded by the Medical Research Future Fund of the Australian government; ClinicalTrials.gov number, NCT04157595.)., (Copyright © 2024 Massachusetts Medical Society.)