Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant mutations in one of 13 confirmed genes. Estimates of MODY prevalence vary widely, as genetic screening is usually restricted based on clinical features, even in population studies. We aimed to determine prevalence of MODY variants in a large and unselected pediatric diabetes cohort. METHODS: MODY variants were assessed using massively parallel sequencing in the population-based diabetes cohort (n = 1363) of the sole tertiary pediatric diabetes service for Western Australia (population 2.6 million). All individuals were screened, irrespective of clinical features. MODY variants were also assessed in a control cohort (n = 993). RESULTS: DNA and signed consent were available for 821 children. Seventeen children had pathogenic/likely pathogenic variants in MODY genes, two diagnosed with type 2 diabetes, four diagnosed with antibody-negative type 1 diabetes (T1DM), three diagnosed with antibody-positive T1DM, and eight previously diagnosed with MODY. Prevalence of MODY variants in the sequenced cohort was 2.1%, compared to 0.3% of controls. CONCLUSIONS: This is the first comprehensive study of MODY variants in an unselected population-based pediatric diabetes cohort. The observed prevalence, increasing access to rapid and affordable genetic screening, and significant clinical implications suggest that genetic screening for MODY could be considered for all children with diabetes, irrespective of other clinical features.

Retrospective Examination of Peripubertal Return for Patients of Western Australia's Gender Diversity Service.

Purpose: Children far in advance of pubertal development may be deferred from further assessment for gender-affirming medical treatment until nearer puberty. It is vital that returning peripubertal patients are seen promptly to ensure time-sensitive assessment and provision of puberty suppression treatment where appropriate. This study investigates (1) how many referrals to the Child and Adolescent Health Service Gender Diversity Service at Perth Children's Hospital are deferred due to prepubertal status; and (2) how many deferred patients return peripubertally. Methods: A retrospective review of all closed referrals to the service was conducted to determine the frequency of prepubertal deferral and peripubertal re-referral. Results: Of 995 referrals received (2014 to 2020), 552 were closed. The reason for closure was determined for 548 referrals (99.3%). Prepubertal status was the second-most frequent reason for closure, and the most frequent for birth-registered males. Twenty-five percent of all deferred prepubertal patients returned peripubertally, before audit closure. A greater return frequency (55.6%) was estimated for those older than 13 years at audit closure. Conclusion: High rates of prepubertal referral indicate the importance of pediatric gender services in providing information, advice, and reassurance to concerned families. With increasing service demand, high rates of return peripubertally have implications for service planning to ensure that returning peripubertal patients are seen promptly for time-sensitive care. Frequency of peripubertal re-referral cannot, however, speak to the stability of trans identity or gender incongruence from childhood to adolescence. Clinics advising prepubertal deferral must proactively plan to ensure that sufficient clinical resources are reserved for this purpose.

Reidentification With Birth-Registered Sex in a Western Australian Pediatric Gender Clinic Cohort.

Importance: Some young people who identify as transgender and seek gender-affirming medical care subsequently reidentify with their sex registered at birth. Evidence regarding the frequency and characteristics of this experience is lacking. Objective: To determine the frequency of reidentification and explore associated characteristics in a pediatric gender clinic setting. Design, Setting, and Participants: This retrospective cohort study examined all referrals to the Child and Adolescent Health Service Gender Diversity Service at Perth Children's Hospital between January 1, 2014, and December 31, 2020. The Gender Diversity Service is the sole statewide specialist service in Western Australia that provides children and adolescents up to age 18 years with multidisciplinary assessment, information, support, and gender-affirming medical care. All closed referrals for this study were audited between May 1, 2021, and August 8, 2022. Exposure: Reidentification with birth-registered sex. Main Outcomes and Measures: The number of referrals closed due to reported reidentification with birth-registered sex was determined, as well as descriptives and frequencies of patient demographics (age, birth-registered sex), informant source, International Statistical Classification of Diseases, Tenth Revision gender-related diagnoses, pubertal status, any gender-affirming medical treatment received, and whether subsequent re-referrals were received. Results: Of 552 closed referrals during the study period, a reason for closure could be determined for 548 patients, including 211 birth-registered males (mean [SD] age, 13.88 [2.00] years) and 337 birth-registered females (mean [SD] age, 15.81 [2.22] years). Patients who reidentified with their birth-registered sex comprised 5.3% (29 of 548; 95% CI, 3.6%-7.5%) of all referral closures. Except for 2 patients, reidentification occurred before or during early stages of assessment (93.1%; 95% CI, 77.2%-99.2%). Two patients who reidentified with their birth-registered sex did so following initiation of puberty suppression or gender-affirming hormone treatment (1.0% of 196 patients who initiated any gender-affirming medical treatment; 95% CI, 0.1%-3.6%). Conclusions and Relevance: These findings from a pediatric gender clinic audit indicate that a small proportion of patients, and a very small proportion of those who initiated medical gender-affirming treatment, reidentified with their birth-registered sex during the study period. Longitudinal follow-up studies, including qualitative self-report, are required to understand different pathways of gender identity experience.

Gender-affirming hormones and surgery in transgender children and adolescents.

The Endocrine Society Clinical Practice Guidelines on the treatment of gender incongruent people recommend the use of gender-affirming cross-sex hormone (CSH) interventions in transgender children and adolescents who request this treatment, who have undergone psychiatric assessment, and have maintained a persistent transgender identity. The intervention can help to affirm gender identity by inducing masculine or feminine physical characteristics that are congruent with an individual's gender expression, while aiming to improve mental health and quality-of-life outcomes. Some transgender individuals might also wish to access gender-affirming surgeries during adolescence; however, research to inform best clinical practice for surgeons and other medical professionals is scarce. This Review explores the available published evidence on gender-affirming CSH and surgical interventions in transgender children and adolescents, amalgamating findings on mental health outcomes, cognitive and physical effects, side-effects, and safety variables. The small amount of available data suggest that when clearly indicated in accordance with international guidelines, gender-affirming CSHs and chest wall masculinisation in transgender males are associated with improvements in mental health and quality of life. Evidence regarding surgical vaginoplasty in transgender females younger than age 18 years remains extremely scarce and conclusions cannot yet be drawn regarding its risks and benefits in this age group. Further research on an international scale is urgently warranted to clarify long-term outcomes on psychological functioning and safety.