Background: The origins of 46,XX ovotesticular DSD remains unclear in the majority of the cases. New genetic tools can help identifying genes and loci involved in gonadal development and differentiation.
Objective and hypotheses: We report the results of the genetic investigations performed in a 15 years old African adolescent with SRY-negative 46,XX ovotesticular DSD.
Method: Clinical evaluation, imaging studies, surgical exploration, histological analysis and genetic investigations including 1 mio Complete Genome Hybridization (CGH)-array were performed to characterize the origin of the DSD.
Results: The patient, who was raised as a boy, was addressed to our consultation at age 15 years. Tanner stages were B4 PH4. External genitalia showed a 4 cm-long phallic structure with penoscrotal hypospadias, completely fused labioscrotal folds, the right one with rugae and containing a palpable gonad, the left one smooth and empty. A common sinus led to the urinary bladder anteriorly and to a vagina posteriorly. Laparoscopy revealed on the right side a hemi uterus, a fallopian tube and an intra-abdominal gonad. The latter was removed: histology revealed an ovary without testicular tissue. Histology of the scrotal gonad was compatible with an ovotestis. Leucocyte and fibroblast karyotype was 46,XX. No SRY could be detected in different tissues, including in leucocytes and gonadal tissue. Mosaicism, chimerism and anomalies in SOX9, WNT4 and R-spondin1 were excluded. CGH-array revealed a heterozygous deletion of 1.7 kb in region 13q31.1 between base pairs positions 81 270 158 and 81 287 901 that was not present in the mother. This non-coding region is highly conserved between species.
Conclusion: To date, the mechanisms leading to ovotesticular DSD are not fully understood. The discovery of a deletion in the highly conserved region 13q31.1 in our patient suggests that this locus could be implicated in the pathogenesis of 46,XX ovotesticular DSD, probably through the regulation of genes implicated in gonadal differentiation.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology