Ambiguidade genital em uma série de casos do ambulatório de distúrbios/diferenças do desenvolvimento do sexo do Hospital Universitário Prof. Alberto Antunes da UFAL - 2008-2018

Abstract

Genital ambiguity (GA) is a phenotype in which the anatomic sex attribution is not clear and belongs to the wide group of disorders/differences of sex development (DSD). The prevalence is of 1:4,500 live births and its aetiology is predominantly genetic. The GA occurs either in individuals with XX, XY normal sexual chromosomes or among those with numerical or structural sexual chromosomes abnormalities. In 2008, at the University Hospital of the Federal University of Alagoas, the DSD ambulatory was initiated. Nowadays this is a regular service delivered by a multidisciplinary team. The aim of this study was to describe the demographic, genetic, and clinical profile of individuals with GA assisted from 2008 to 2018. Data was gathered using a unique protocol and database. The karyotype was a universal test. The AR, SRD5A2, HSD17B3, NR5A1, and CYP21A2 genes analyses were performed according to clinical indication, after the karyotyping. During this period, 146 individuals with DSD were seen, 73 (50%) of which with GA, belonging to 71 families, 21.9% living in Maceió. Parental consanguinity and phenotype recurrence were observed in 16.9% and 14.1%, respectively. Age at the first specialized assessment was over 90 days of life (inadequate) for 56.2% of the sample, and 78.1% presented moderate to severe AG. Disorders of androgen synthesis or action (DSD XY) were the largest group (50.7%), followed by androgen excess (32.9%) and the disorders of gonadal differentiation (DGD) (16.4%). Congenital adrenal hyperplasia was the most prevalent nosology (32.9%). New variants in HSD17B3, NR5A1, and CYP21A2 genes were identified. Among DGD, two rare cases of Klinefelter Syndrome plus ovotesticular DSD, and gonadal mixed dysgenesis plus Down Syndrome were identified. This is the first description of the demographic, genetic, and clinical profile of GA in Alagoas. Overall data corroborate the literature. The study has also identified rare and new aetiologies which may contribute to rise the knowledge on DSD. These results inform the debate on health policies for patients with GA in Alagoas.