INTERSEX
Silink M
The Children's Hospital at Westmead, Sydney,
Australia
Intersex is a neonatal emergency. Gender
assignment is not possible without urgent investigation in a specialized
centre (chromosome analysis, imaging by ultrasound and genitogram contrast
studies, hormone studies and subsequent genetic studies if indicated).
Life-threatening medical conditions (various forms of congenital adrenal
hyperplasia) need rapid exclusion. Decision making is helped by
characterizing the chromosomal sex (46 XX, 46 XY, other), gonadal sex
(testis, ovary, ovotestis, dysgenetic), internal duct sex (Wolffian,
Mullerian) and external duct sex (male, female, indeterminate). Treatment
needs to be individualized and may involve gender assignment, hormone replacement
and reconstructive surgery. The timing and extent of surgery is a question
under vigorous debate with a greater emphasis on the patient's rights to be
part of the treatment recommendation.
Sexual differentiation involves many genes
controlling a cascade of events affecting gonads, Mullerian and Wolffian
structures, urogenital sinus, external genitalia and the CNS. Genes
important in the differentiation of the indifferent gonad include WT1 and
SF-1. The DSS locus is important for ovarian differentiation. Testis
differentiation is dependent on SOX-9 expression. SF-1 also has a role in
activating Mullerian Inhibitory Substance gene expression in the developing
testis. Wolffian duct and male genital development are dependent on
testosterone action (synthesis of testosterone and dihydrotestosterone,
binding to androgen receptors, nuclear translocation, and subsequent gene
expression). Gender identity seems to be a hormonally dependent process in
the CNS.