Which of these do not occur in a child with a disorder of sexual differentiation?
A. 21 α hydroxylase deficiency is associated with 46XX karyotypeAnswer E
For those that do not practice in this area, disorders of sexual differentiation (DSD) can prove difficult to understand. It would seem unfair that someone taking the FRCS(Urol) would have a detailed knowledge of the classification of these conditions. A few basic principles will be outlined.
A very simplified account of the embryology of differentiation follows. The foetus will develop by default into a female. The mesonephric duct (precursors of uterus and upper vagina) are initially present in both males and females. Secretion of Müllerian Inhibiting Substance (MIS) from the Sertoli cells from 7 weeks will cause regression of the mesonephric duct structures in boys. Androgens, and especially dihydroxy-testosterone are responsible for the development of the external genitals in males.
A good starting point for classifying DSD is the karyotype. Those with 46XX who have DSD will be over-virilised; those with 46XY who have DSD will be under-virilised. This will be further complicated by mosaic karyotype patterns. The next consideration is the development of the gonads. Where gonads have formed abnormally there is gonadal dysgenesis. This may be complete or partial. It may result in streak gonads or in an ovo-testis combination.
Then next consideration is whether there is an abnormality in the synthesis of the sex-hormone or their receptor. In congenital adrenal hyperplasia, the production of cortisol and aldosterone is disrupted triggering over production of ACTH which then stimulates overproduction of androgenic precursors resulting in over virilisation of girls. Androgen receptor insensitivity and 5α reductase deficiency will on the other hand result in under-virilised boys.
Ovarian dysgenesis syndrome is also known as Turner’s syndrome. Dysgenetic streak ovaries are present but in the absence of a Y chromosome there is no cause for ambiguity about the appearance of the genitals.