ESPE Abstracts

Introduction: The 46,XX testicular disorder of sex development (DSD) is a rare genetic condition and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients, but approximately 20% of patients are SRY-negative. We report a 1.3 -year old SRY/negative 46,XX boy with complete sex reversal caused by SOX3 duplication.

Case report: A 1.3-year-old boy was referred for clinical evaluation and additional diagnostic workup of cryptorchidism. He was born from the mother's fifth pregnancy, in term, with elective cesarean section. His birth weight was 3770g, birth length 50 cm . The absence of testicles in the scrotum was noticed at the first physical exam after the delivery, and on several occasions during the first year of life. The testicular tissue was not visualised by ultrasound neither intra-abdominal nor in the inguinoscrotal region. On the first pediatric endocrinology evaluation, the boy had a body length of 75 cm (3.c, -1.8 SDS) and a body weight of 8.78 kg (weight for height 89%) without gross anomalies in clinical status. The external genitalia were male, penis size 2 cm, pubarche I Tanner stage, the distance from the root of the penis to the anus was 6.5 cm, and the scrotum was hypoplastic, empty, without palpable gonads in the inguinal canal. Basic laboratory assessment included: LH (luteinizing hormone) <0.1 IU/l, FSH (follicle-stimulating hormone) 1.6 IU/l, testosterone <0.4 nmol/l, AMH (anti-Mullerian hormone)> 164 pmol/l, and cytogenetic analysis: 46,XX karyotype. The normal value of AMH confirmed testicular tissue, which had not been visualized until then. In order to assess the functional capacity of the testes, hCG test was performed after which testosterone levels rose to 8.4 nmol/L. Pelvic ultrasound did not reveal uterus, ovary and other Mullerian structures. Additional cytogenetic analysis and in situ hybridization did not identify the SRY region. Chromosomal Microarray Analysis proved duplication in Xq27.1 region containing only SOX3 gene and confirmed the cause of the described phenotype in the patient.

Conclusion: This case emphasizes the need for additional genetic investigation in SRY-negative XX sex-reversed individuals and indicates that SOX3 is the evolutionary antecedent of sex-determining region Y. An accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.