Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.

ContextIn 46,XY disorders of sexual development (DSD) patients, several factors may affect psychosexual development, leading to gender identity discrepancy and gender change later in life. Prenatal sexual steroid exposure and external genital virilization are considered to influence human psychosexual development, but their roles not completely understood yet.DesignA total of 144 individuals (18 to 60 years of age) with a clinical/molecular diagnosis of 46,XY DSD from a single tertiary center were enrolled. Psychosexual outcomes (gender role, gender identity, and sexual orientation) were assessed using questionnaires and psychological test. The Sinnecker score was used for genital virilization measurement. Prenatal androgen exposure was estimated according to 46,XY DSD etiology.ResultsWe found a positive association between prenatal androgen exposure and male psychosexual outcomes. Alternatively, prenatal estrogen exposure, age of gonadectomy, and the degree of external genital virilization did not influence any psychosexual outcome. There were 19% (n = 27) with gender change, which was associated with prenatal androgen exposure (P < 0.001) but not with the external genital virilization. The median age of gender change was 15 years, but most of the patients reported the desire for gender change earlier.ConclusionsPrenatal androgen exposure influenced psychosexual development in 46,XY DSD favoring male psychosexuality in all psychosexual outcomes, whereas the degree of external genital virilization did not influence these outcomes. The organizational effect of sexual steroids on psychosexuality at puberty appears to be weak in comparison with the prenatal effects. Prenatal androgen exposure also influenced female-to-male gender change frequency. All 46,XY DSD conditions with prenatal androgen exposure must be followed for gender issues in their management.

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Context Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data for diagnosing 46,XY DSD. Objective to analyze the contribution of phenotypic classification either alone or in association with genetic evaluations, mainly MPS, for diagnosing a large cohort of 46,XY DSD patients. Design/ patients 209 non-syndromic 46,XY DSD index cases from a Brazilian DSD center were included. Patients were initially classified into three subgroups according to clinical and biochemical data: gonadal dysgenesis (GD), disorders of androgen secretion/action, and DSD of unknown etiology. Molecular genetic studies were performed by Sanger sequencing and/or MPS. Results Clinical/biochemical classification into either GD or disorders of hormone secretion/action was obtained in 68.4% of the index cases. Among these, a molecular diagnosis was obtained in 36% and 96.5%, respectively. For the remainder 31.6% classified as DSD of clinically unknown etiology, a molecular diagnosis was achieved in 31.8%. Overall, the molecular diagnosis was achieved in 59.3% of the cohort. The combination of clinical/biochemical and molecular approaches diagnosed 78.9% of the patients. Clinical/biochemical classification matched with the genetic diagnosis in all except one case. DHX37 and NR5A1 variants were the most frequent genetic causes among patients with GD and DSD of clinical unknown etiology, respectively. Conclusions The combination of clinical/biochemical with genetic approaches significantly improved the diagnosis of 46,XY DSD. MPS potentially decreases the complexity of the diagnostic workup as a first-line approach for diagnosing 46,XY DSD.

Objective: Discrimination and bullying are common conditions among LGBT people. During schooling, these practices compromising education. The aim of this study is to evaluate educational attainment among Brazilian transgender women (TW) and how their education level affects the risk of HIV infection. Study design: a cross-sectional population-based study. Subjects and methods: 95 adult TW were selected. Information concerning verbal and physical aggression, school dropout, school years (SY), and educational level were assessed. HIV status was screened using a fourthgeneration immunoassay followed by western blot testing. Results: The mean of SY was 9.1 ± 3.8 ys. The mean age at school dropout was 16.3 ± 3.4 ys old. Verbal aggression was reported by 83%, physical by 48%, and 18% of the TW dropped out school immediately after being physically assaulted. Participants who suffered physical aggression attended school for almost 4 years less than those participants who did not suffer this abuse (OR =-3.96, p < 0.0001). A similar result was found for verbal aggression (OR =-4.35; p < 0.0001). HIV/AIDS prevalence was 18% (n = 17). The mean of SY among HIV/AIDS positive and negative individuals were 6.8 ± 43 versus 9.7 ± 3, respectively (p = 0.004). Lower education was associated with higher frequency of HIV/AIDS among TW and this relationship was sustained after adjustment for injectable drug use and sex work (OR = 0.79, p = 0.04). Conclusion: Among Brazilian TW, lower education level was a risk factor associated with HIV. The reasons for low schooling among TW are multifactorial, but verbal and physical harassment strongly contribute for it.

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A HAC é um distúrbio congênito, caracterizado pela deficiência na biossíntese do cortisol, associado ou não à deficiência de aldosterona e, consequentemente, à superprodução de andrógeno. Essa condição afeta igualmente homens e mulheres. No sexo feminino, acarreta virilização da genitália externa em graus variados. No sexo masculino, nenhuma anormalidade se apresenta fenotipicamente ao nascimento. Tradicionalmente, o tratamento dessa síndrome consiste na reposição diária de glicocorticoides e mineralocorticoides. Novas terapias têm sido propostas com  intuito de se obterem resultados mais satisfatórios; dentre elas, existem: análogos do LHRH, GH, inibidores da aromatase, antiandrógenos e a adrenalectomia. Resultados preliminares apontam para uma melhora da altura final e do manejo clínico dos pacientes submetidos aos novos tratamentos. O objetivo deste estudo foi revisar a literatura acerca dessas novas modalidades terapêuticas, com o intuito de explorar o que há de mais novo na abordagem dessa síndrome.

Background: Molecular biology and cytogenomics methods have gained space in the clinical investigation for patients with disorders/differences in sexual development (DSD). Here we aimed to evaluate the role of SNP-array in achieving a molecular diagnosis in a sample of 22 Brazilian patients with syndromic DSD of unknown etiology, and to compare the relationship between the clinical diagnosis and the SNP-array results.Methods: 22 patients with DSD associated with syndromic features in several systems other than the genital tract were included in the study and underwent search for genomic copy number variations (CNVs) by SNP-array.Results: In two patients, the diagnosis of 46,XX SRY+ DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and 13q33.1 deletion encompassing the FGFR2 and the EFNB2 gene were associated with genital atypia and syndromic characteristics in two patients with 46, XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataract, a 12Kb deletion on chromosome 10 was found, justifying the congenital cataract.Conclusions: The SNP-array technique identified the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD. In one patient the array contributed to partially clarify the patient's syndromic phenotype, but not the genital atypia.