Embryonic testicular regression sequence: A part of the clinical spectrum of 46,XY gonadal dysgenesis

We report on a group of 9 subjects who had a 46,XY karyotype, ambiguous genitalia, abnormalities of sexual duct formation, and lack of gonadal tissue on one or both sides. This is sometimes referred to as 'embryonic testicular regression.' Previous investigators have suggested that this condition results from loss of testes at a critical stage in development. We examined the possibility that the 'embryonic testicular regression' is part of the clinical spectrum of 46,XY gonadal dysgenesis. Four subjects totally lacked gonadal tissue, three of them having ambiguous genitalia, and one a micropenis. The development of incongruous sexual ducts (presence of Mullerian ducts in the subject with micropenis, and absence of Mullerian and Wolffian ducts in two subjects with ambiguous genitalia) suggests that the embryonic gonads were intrinsically functionally abnormal before their disappearance. Five subjects had unilateral gonadal tissue, ambiguous genitalia, and a mix of Wolffian and Mullerian structures. The development of incongruous sexual ducts in 3 of them, the presence of ambiguous external genitalia in 5, and the presence of abnormal gonadal histology in 2 patients all indicate an underlying abnormality of gonadal differentiation in these subjects. The occurrence of testicular regression in several subjects in the family of one patient suggests a genetic basis for the condition. The presence of multiple congenital anomalies in other subjects in our study suggests either a mutation in a single gene that functions in several developmental pathways, or a defect of multiple genes that might be the result of a chromosome deletion. The sex-determining region Y (SRY) gene was sequenced in five subjects and was normal in all of them, suggesting that the underlying genetic abnormality in these subjects is located in one of several genes that function subsequent to SRY in the early stages of testis differentiation.