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 associated with primary amenorrhea. Only two unrelated cases of isolated partial gonadal dysgenesis with molecular characterization have been reported. The risk of gonadoblastoma is high.
Objective and hypotheses: Phenotype correlation study (clinical, hormonal, and histological) and genotype size DAX1 duplication could be decisive of the degree of gonadal dygenesis and oncological risk.
Method: Description of four cases of a family with several cases are know to six generations. All four cases hat hypomasculinisation of external genitalia. The age of diagnosis were14 years 11 years and two in antenatal period. The absence of Mullerian structure was observed. The sex rearing differs: on was reared as girl but changed as boy at puberty (14 years old) and deceased at 70 years old; two reared as girl; the latest reared as boy after a collegiate decision. Biological data in neonatal period two cases have confirmed the diagnosis of partial gonadal dysgenesis with low AMH, but normal testosterone response to hCG test. Bilateral gonadectomy have been done in patients reared as girl At 13 months, gonads were hypoplasic and showed subnormal testicular structure, at 11 years the gonads (V.1) were more dysplasic.
Results: 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. The phenotype of our cases is that of partial gonadal dysgenesis.
Conclusion: The explanation of the isolated partial gonadal dysgenesis vs pure gonadal dysgenesis with high risk of gonadoblastoma be could the location and the extend of this NR0B1 duplication. These data suggested the screening of this duplication in all cases of partial 46,XY gonadal dysgenesis.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology