Answers 1 and 2 and 3 might be considered in the differential, with 2 being the most likely. The most common form of congenital adrenal hyperplasia (CAH), 21-hydroxylase deficiency, typically presents with ambiguous genitalia on ultrasound and a female karyotype.
Individuals with 46, XX testicular disorder of sex development (46, XX testicular DSD), which is sometimes still referred to as 46, XX male syndrome, have a female karyotype, male external genitalia, two testicles, azoospermia and absence of Mullerian structures. The majority demonstrate the presence of SRY (sex-determining region of Y) within their genome, most commonly on one of the X chromosomes.
Maternal cell contamination (MCC) is also a possibility, although it commonly manifests as 46, XX/46, XY mosaicism.
The genotype-phenotype discordance in answer 4, androgen insensitivity (AI), is that of a normal male karyotype and normal female external genitalia.
In view of rare reports of syndromic testicular DSD involving microdeletions of Xp on the derivative (der) X-chromosome as the consequence of the recombination event, microarray testing as well as FISH confirmatory testing was performed to rule out deletions within the steroid-sulphatase (STS) as well as Kallmann regions. Results indicated that no deletions were detected.
In addition, the presence of SRY on Xp typically occurs de novo, but rare cases of inheritance have been described. For reassurance, both parents were karyotyped and had SRY FISH studies performed, which revealed results expected for a normal male and female.
The family should be counseled that the natural history of this presentation of 46, XX testicular DSD is expected to be that of a male phenotype and identity with concerns related to delayed puberty, hyphotrophic hypogonadism and likely infertility, but without learning and behavior problems or developmental delay.
Long-term implications center on the above-mentioned issues of puberty and management of hyphotrophic hypogonadism. Testosterone replacement therapy might be indicated. Infertility is expected.
A multifaceted approach of clinical care and anticipatory guidance provided by a multidisciplinary team including urology, endocrinology and genetics, as well as psychology, is best suited to meet the needs of this population. Psychological support is important throughout, but especially so at and around the time of disclosure.