ESPE Abstracts

We report two patients with 45,X/46,X, idic (Y) gonadal dysgenesis (GD) diagnosed at birth based on genotype-phenotype discordance identified in the routine clinical follow-up during early pregnancy. Genotypic sex, as determined by cell free DNA testing was 45 XO in the first patient while phenotypic sex was male. Second patient was found to have a 46, XX genotype with SRY detected through rhesus incompatibility screening, while phenotypic sex was female. Postnatal karyotype and fluorescence in situ hybridization (FISH) in the first patient confirmed the mosaicism: mos 46,X,idic(Y)(q11.2)[17]/45,X[13]. Clinical examination revealed male genitalia with distal hypospadia. The two gonads were in the scrotum and penis length was normal. The external masculinization score (EMS) was evaluated at 11,5. Hormonal evaluation at birth showed: LH 0.6 IU/L and FSH 1.4 IU/L. Estradiol was undetectable and testosterone level was 78.8 ng/dl. AMH level was 42.5 µg/L. LH and FSH values increased at 2.3 U/L and 1.3 U/L respectively during mini-puberty with testosterone level reaching 288.2 ng/dl. AMH value was 136 µg/L and Inhibin B value was 329.4 ng/L. Postnatal karyotype and FISH in the second patient confirmed the mosaicism: mos 46,X,idic(Y)(q11.2)[18]/45,X[12]. Clinical examination showed female genitalia with an enlarged clitoris. There were no palpable gonads. EMS was evaluated at 3. At birth, levels of LH, FSH and estradiol were undetectable. Testosterone was very low at 0.16 nmol/L. 17-OH-Progesteron was normal (2.5 nmol/L). AMH value was very low at 1.95 µg/L and Inhibin B value was 29.6 ng/L. Abdominal ultrasound showed a uterus with no visualized ovaries. At 2 months, this patient presented inguinal tumefaction caused by inguinal hernia. Because of gonadal tumor risk, gonadectomy in combination with surgical hernia repair was performed. Right gonadal histology revealed a streak gonad with gonadoblastoma and left gonad was considered an ovotestis with gonadoblastoma. Individuals with 45,X/46,X, idic (Y) GD have a highly variable phenotype. Clinical presentation as well as gonadal germ cell tumor risk depends on several parameters including isodicentric Y chromosome breakpoints and percentage of mosaicism, especially in gonadal tissue cells. Multidisciplinary approach is crucial for prenatal genetic counselling and long term follow-up regarding sex assignment, gonadal function and gonadal tumor risk evaluation. Indeed, identification of noninvasive early predictor factors for early-stage tumor detection are still currently lacking and gonad management remains a challenge.