ESPE Abstracts

We report mosaic triploidy 69XXY/46XX in ovotesticular DSD which poses significant diagnostic and management questions.

Case: A baby born to non-consanguineous parents after a normal pregnancy, presented with atypical genitalia including significant clitoromegaly, a urethral opening in the anterior perineum and a normal vaginal opening. Bilateral masses were noted in the labio-scrotal folds. Pelvic ultrasound identified a normal uterus however the gonads could not be characterised as ovaries or testes. The blood karyotype was 46XX. Androgens and urine steroid profile were normal. Inhibin B and anti-Mullerian hormone results, at 149 ng/l and 280.2 pmol/l respectively, were abnormal for a child with a 46XX karyotype. These results suggested 46XX ovotesticular DSD. A female sex of rearing was decided in conjunction with parents and further investigations undertaken. A 30-gene DSD panel identified a heterozygous sequence variant c.389C>T in the NR5A1 gene. Heterozygous variants in the NR5A1 gene have recently been described in association with 46,XX ovotesticular DSD but as this variant was subsequently identified in her father its relevance was unclear. The role of gonadal biopsy was discussed and as the child had inguinal herniae, an examination under anaesthetic was undertaken. The left ovary appeared normal and was not biopsied. Normal Mullerian structures were confirmed and no Wolffian structures were present. The right gonad however appeared bilobar and abnormal, and biopsy demonstrated clearly demarcated ovarian and testicular histology. Cytogenetic testing showed mosaicism for a triploid 69XXY and 46XX cells within the right gonad. The presence of the Y chromosome in the abnormal gonad was thought to be sufficient explanation for virilisation, rather than the NR5A1 variant. Two possible mechanisms were postulated for this apparently localised triploidy: either the foetus was initially triploid with subsequent trisomic rescue in some cells, or a chimera resulting from two sperm fertilising one ovum. Optimal management of the gonads remains a significant question. Her atypical right gonad is likely to cause virilisation and may pose a risk of malignancy in the future. These factors and poor fertility potential, support its removal, but the management of the left ovary is controversial. It appears normal with potential for fertility, but has an unknown risk of malignancy. A biopsy carries risk of injury compromising future fertility and could yield only localised information. The decision currently is to watch and undertake surveillance of the left ovary, however the optimal surveillance method and long term management remains a concern.