46,XX DSD: Developmental, Clinical and Genetic Aspects

Abstract

Differences in sex development (DSD) in patients with 46,XX karyotype occur by foetal or postnatal exposure to an increased amount of androgens. These disorders are usually diagnosed at birth, in newborns with abnormal genitalia, or later, due to postnatal virilization, usually at puberty. Proper diagnosis and therapy are mostly based on the knowledge of normal development and molecular etiopathogenesis of the gonadal and adrenal structures. This review aims to describe the most relevant data that are correlated with the normal and abnormal development of adrenal and gonadal structures in direct correlation with their utility in clinical practice, mainly in patients with 46,XX karyotype. We described the prenatal development of structures together with the main molecules and pathways that are involved in sex development. The second part of the review described the physical, imaging, hormonal and genetic evaluation in a patient with a disorder of sex development, insisting more on patients with 46,XX karyotype. Further, 95% of the etiology in 46,XX patients with disorders of sex development is due to congenital adrenal hyperplasia, by enzyme deficiencies that are involved in the hormonal synthesis pathway. The other cases are explained by genetic abnormalities that are involved in the development of the genital system. The phenotypic variability is very important in 46,XX disorders of sex development and the knowledge of each sign, even the most discreet, which could reveal such disorders, mainly in the neonatal period, could influence the evolution, prognosis and life quality long term.

A 22q13.1 duplication in mosaicism including SOX10

“…Full or partial duplication of chromosome 22 has long been described as associated with diverse features including varying degrees of masculinization in 46,XX individuals. SOX10 overexpression has been proposed as the mechanism underlying the last observation (Alkhzouz et al, 2021;Bashamboo & McElreavey, 2013;Polanco et al, 2010). It also appears that, depending on the location and size of the duplicated region, some features can overlap with WS.…”

Determination of Barr bodies in Transgender Patients in India – A comparative study

“…The 3 subjects who were found to be chromatin positive could have chromosomal aberrations like 47 XXY with female gender identity, true hermaphrodite with predominant XX and a female gender or 46XX with CAH, 45 XO/46 XX mosaicism. [ 15 16 ]…”

XX Male: Early Detection With Prenatal Testing

“…The SRY gene is then expressible, resulting in the production of anti-Mullerian hormone (AMH), which is responsible for the degeneration of the Mullerian ducts and promoting the development of the Wolffian ducts, for female and male gonadal development, respectively. Therefore, a 46,XX genotype can result in a male phenotype due to the promotion of Wolffian duct development from SRY expression on the X chromosome, which is elucidated elsewhere [ 6 ]. The main complication is testicular dysfunction resulting in hypergonadotropic hypogonadism.…”

“…The main complication is testicular dysfunction resulting in hypergonadotropic hypogonadism. This is due to non-functional gonads, with the only source of steroidogenesis occurring in the adrenal glands and peripheral adipose tissue [ 6 ]. Associated with this diagnosis is azoospermia, which has been well documented [ 7 , 8 ].…”