A deep intronic mutation in AR gene causing androgen insensitivity syndrome: difficulties of diagnostics

Partial androgen resistance syndrome (PAIS) is the most difficult form of disorders/differences of sex development 46,XY (DSD 46,XY) for choosing of patient management. To date, there are no clear biochemical criteria, especially before puberty, that allow differentiating PAIS from other PAIS-like forms of DSD 46, XY, and genetic verification of the partial form of AIS plays an important role. Meanwhile, according to the literature, mutations in the coding region of AR gene have not been identified in more than 50% of patients with suspected AIS. We performed an extensive analysis of the AR gene in a patient with clinical and laboratory signs of AIS and found a deep intron mutation in the AR gene (p. 2450–42G>A). This variant creates an alternative splice acceptor site resulted a disturbance of the AR function. These findings indicate the need for extensive genetic analysis in a cohort of patients with suspected CPA in the absence of mutations in the AR gene using standard methods of genetic diagnosis.

Atypical Athletic Corporeality and Clinical Embodied Deviance: A Case Study of Dutee Chand

The paper outlines the politics of gendered athleticism appropriated and instrumentalised through the medico-juridical apparatus of the sports governing bodies. The biomedical discourse governing the atypical athletic body and the embodied nature of its pathologised deviancy is drawn through the critical reflection of athletic regulatory bodies’ testing regimes and policies. It is through the detailed analysis of the Indian sprinter Dutee Chand’s case that one of many confounding disqualification charges and trials of hyperandrogenism against athletes with differences of sex development (DSD’s) is foregrounded. Drawing on the critical scholarship of gender theorists and activists, the legitimacy of the stipulated biological mechanism of testosterone as a regulatory performance index in female elite sport is contested and problematized. Pertinent here is Dutee Chand’s narrative of trial and triumph that destabilises the reductive embodiments of sex institutionalised in and beyond the sporting track. Significantly, the paper also delineates the premises of the constitutive exclusionary and arbitrary regulatory regimes propounded by the athletic governing bodies like the International Association of Athletics Federations (IAAF) and the International Olympic Committee (IOC). These concerns border on the geopolitics of race and nation framing the normative, prescriptive and reserved rights of femininity, able-bodiedness and heteronormativity in international women’s elite sport.

Condition openness is associated with better mental health in individuals with an intersex/differences of sex development condition: structural equation modeling of European multicenter data

Background Openness on one's health condition or (stigmatized) identity generally improves mental health. Intersex or differences of sex development (DSD) conditions have long been kept concealed and high levels of (internalizing) mental health problems are reported. This study examines the effects of condition openness on anxiety and depression and the role of mediating concepts in this population. Methods Cross-sectional data of individuals of 16 years and older with an intersex/DSD condition was collected in 14 specialized European clinics as part of the dsd-LIFE study. Patient-reported measures were taken on openness and shame (Coping with DSD), self-esteem (Rosenberg Self-Esteem Scale), satisfaction with care (CSQ4), anxiety and depression (HADS). Scores were compared per clinical group and data were analyzed via structural equation modeling (SEM) to calculate prediction and mediation models. Results Data of 903 individuals were included in this study (Turner syndrome (n = 284), 46, XY DSD (n = 233), CAH (n = 206) and Klinefelter syndrome (n = 180)). Participants were moderately open on their condition. High levels of both anxiety and depression were observed across the sample. In SEM analysis, the tested models predicted 25% of openness, 31% of anxiety and 48% of depression. More condition openness directly predicted lower anxiety and depression symptoms, as well as indirectly through increased self-esteem, self-satisfaction and satisfaction with social support. Conclusions Condition openness is associated with lower anxiety and depression in individuals with an intersex/DSD condition. Healthcare may provide the necessary knowledge and skills to employ one's optimal level of self-disclosure in order to improve mental health.

Pubertal development in 46,XY patients with NR5A1 mutations

Purpose Mutations in the NR5A1 gene, encoding the transcription factor Steroidogenic Factor-1, are associated with a highly variable genital phenotype in patients with 46,XY differences of sex development (DSD). Our objective was to analyse the pubertal development in 46,XY patients with NR5A1 mutations by the evaluation of longitudinal clinical and hormonal data at pubertal age. Methods We retrospectively studied a cohort of 10 46,XY patients with a verified NR5A1 mutation and describe clinical features including the external and internal genitalia, testicular volumes, Tanner stages and serum concentrations of LH, FSH, testosterone, AMH, and inhibin B during pubertal transition. Results Patients who first presented in early infancy due to ambiguous genitalia showed spontaneous virilization at pubertal age accompanied by a significant testosterone production despite the decreased gonadal volume. Patients with apparently female external genitalia at birth presented later in life at pubertal age either with signs of virilization and/or absence of female puberty. Testosterone levels were highly variable in this group. In all patients, gonadotropins were constantly in the upper reference range or elevated. Neither the extent of virilization at birth nor the presence of Müllerian structures reliably correlated with the degree of virilization during puberty. Conclusion Patients with NR5A1 mutations regardless of phenotype at birth may demonstrate considerable virilization at puberty. Therefore, it is important to consider sex assignment carefully and avoid irreversible procedures during infancy.