46,XY karyotype in a female phenotype fetus: a challenging diagnosis

The growing use of prenatal investigations allows an early detection of several inborn disorders, including disorders of sexual development. The management of these conditions is an arising problem.

46,XY karyotype and female phenotype were detected in a fetus; 5α-reductase and androgen receptor gene analysis on chorionic villi revealed no relevant mutation. The newborn was assigned to female sex. The diagnosis of 17β-hydroxysteroid dehydrogenase-3 β-OL deficiency was reached at four months of age, by means of a low testosterone/Δ 4-androstenedione ratio after HCG test and HSD17B3 gene analysis.

A 46,XY fetus with female external genitalia suggests different conditions, some very rare. Specific genetic investigations should be performed prenatally when possible. A complete evaluation is mandatory after delivery to reach a correct diagnosis.