34. Chromosomal microarray characterization of a prenatal case of 46,XX SRY-positive Disorder of Sex Development (DSD)

      Nonsyndromic SRY-positive testicular 46,XX disorder of sex development (DSD) is most frequently de novo. Affected individuals often have normal male external genitalia and present as adults with infertility, or come to clinical attention after puberty due to signs of undermasculinization. Genital anomalies range from small testes to cryptorchidism, micropenis, and/or hypospadias to presence of both testicular and ovarian tissue (ovotesticular DSD or true hermaphroditism). Diagnosis is typically made by chromosome analysis showing a 46,XX karyotype and metaphase fluorescence in situ hybridization (FISH) demonstrating an SRY signal translocated to a derivative X chromosome. We present the case of a prenatally diagnosed 46,XX SRY-positive DSD. The amniotic fluid sample was submitted for testing due to evidence of fetal gender discordance, specifically cffDNA results indicated a female fetus but 20w6d gestation ultrasound images were most consistent with male genitalia. In addition to typical cytogenetic and FISH diagnostic testing, SNP chromosomal microarray (CMA) was utilized to further characterize the Xp;Yp translocation of the derivative X chromosome. CMA detected the presence of Yp11.31-p11.2 including SRY, along with duplication of the proximal part of the pseudoautosomal region (PAR1) of Xp. CMA data allowed estimation of Xp and Yp breakpoints. We compare our findings with the variable translocation breakpoints from de novo and extremely rare inherited cases reported in the literature. Review of previously reported genotype-phenotype correlation has shown genetic complexity of this region and phenotypic variability among individuals with Xp;Yp rearrangements. Therefore an understanding of the phenotypic outcome for this pregnancy proved challenging. However, given that parental cytogenetic and metaphase FISH studies were normal, supporting a de novo event, the parents could be reassured of a low recurrence risk for future pregnancies.
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