Several karyotypes can create a coexistent ovary and testis, and thus ovotesticular DSD is found in all three DSD categories (see Table 3-2). In the sex chromosome group, ovotesticular DSD may arise from a 46,XX/46,XY karyotype. Here, an ovary, testis, or ovotestis may be paired. he phenotype in general mirrors that for ovotesticular disorders, which are described earlier on this page.
For others in the sex chromosome DSD group, ovotesticular disorder arises from a chromosomal mosaic such as 45,Xl46,XY. With this karyotype, a picture ofmixed gonadal dysgenesis shows a streak gonad on one side and a dysgenetic or normal testis on the other. The phenotypical appearance ranges from undervirilized male to ambiguous genitalia to Turner stigmata.
• 46,XY Disorders of Sex Development
Insuicient androgen exposure of a ferus destined to be a male leads to 46,XY DSD-formerly called male pseudohermaphroditism. he karyotype is 46,XY and testes are frequently present. he uterus is generally absent as a result of normal embryonic AMH production by Sertoli cells. hese subjects are most often sterile from abnormal spermatogenesis and have a small phallus that is inadequate for sexual function. As seen in Table 3-2, etiology of 46,XY DSD may stem from abnormal testis development or from abnormal androgen production or action.
46,XY Gonadal Dysgenesis his spectrum of abnormal gonad underdevelopment includes pure or complete, partial, or mixed 46,XY gonadal dysgenesis. These are deined by the amount of normal testicular tissue and by karyotype. Because of the potential for germ cell rumors in dysgeneric testes and intraabdominal testes, afected patients routinely have been advised to undergo gonadectomy Giang, 2016).
Of these, pure gonadal dysgenesis results from a mutation in the SRY gene or in other genes with testis-determining efects (Hutson, 2014). his leads to underdeveloped dysgenetic gonads that fail to produce androgens or AMH. Formerly named Swyer syndrome, the condition creates a normal prepubertal female phenotype and a normal miillerian system due to absentiAMH.
Partial gonaal dysgenesis deines those with gonad development intermediate between normal and dysgenetic testes. Depending on the percentage of underdeveloped testis, wolian and miille rian structures and genital ambiguity are variably expressed.
Mixed gonadal dysgenesis is one type of ovotesticular disorder of sexual diferentiation. As discussed on page 39, one gonad is streak, and the other is a normal or a dysgenetic testis. Of afected individuals, 15 percent have a 46,Y karyotype (Nistal, 20 15 b). The phenotype is wide ranging as with partial gonadal dysgenesis.
Last, testicular regression can follow initial testis development. A broad phenotypic spectrum is possible and depends on the timing of testis failure.
In some cases, 46,Y disorders of sexual diferentiation stem from abnormalities in: (1) testosterone biosynthesis, (2) LH receptor function, (3) AMH function, or (4) androgen receptor action. First, the sex steroid biosynthesis pathway can sufer enzymatic defects that block testosterone production. Depending on the timing and degree of blockade, undervirilized males or phenotypic females may result. In contrast to these central enzymatic defects, peripheral defects may be causative. Namely, abnormal 5-. reductase type 2 enzyme action leads to impaired conversion of testosterone to DHT and thus to undervirilization.