Background: Isolated gonadal dysgenesis due to NR0B1 locus duplication is a rare cause of 46,XY DSD. Almost reported cases were a total gonadal dysgenesis with complete female phenotype and streak gonad diagnosed late because of absent of pubertal development and primary amenorrhea. Only two unrelated cases of isolated partial gonadal dysgenesis with molecular characterization have been reported. The risk of gonadoblastoma is high.
Family case reports: All four cases (II.4, V.1, V.8, and V.I2) have a 46,XY DSD with external ambiguous genital (variable partial labial fusion, one urogenital orifice, and undervirilized tubercule). The age of diagnosis were 14 years (II.4), 11 years (V1), and antenatal (V.8, and VI.2) period. The absence of uterus and Mullerian structure was observed and suggest functional Sertoli cells in antenatal sex differentiation period. The sex rearing differs: II.4 was reared as girl but changed as boy at puberty (14 years old) and deceased at 70 years old; V.1 and V.8 reared as girl; VI.2 reared as boy after a collegiate decision (parents, medical, surgical, and psychologist professionals). Biological data in neonatal period of V.8 and VI.2 cases have confirmed the diagnosis of partial gonadal dysgenesis with low but detectable AMH, normal testosterone response to hCG test. Bilateral gonadectomy has been done in patients V.1 and V.8. At 13 months, gonads (V.8) were hypoplasic and showed subnormal testicular structure with abundant seminiferous tubules but few germinal cells. AMH was highly positive in Sertoli cells, at 11 years the gonads (V.1) were more dysplasic.
Molecular studies: No mutation has been found in AR gene and several other genes (SF1, …). This duplication of the NR0B1 gene detected by MLPA and bordered by CGH array was about of 452 kb including NR0B1 and four MAGEB genes, but not CXorf21 and GK genes.
Conclusion: The explanation of the isolated partial gonadal dysgenesis vs. pure gonadal dysgenesis with high risk of gonadoblastoma could be the location and the extend of this NR0B1 duplication. These data suggest the screening of this duplication in all cases of partial 46,XY gonadal dysgenesis.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology