Antenatally determined sesquizygosity in gender discordant monochorionic diamniotic twins (46,XX/46,XY):-postnatal clinical and gonadal phenotype

Abstract

Objectives: Sesquizygosis is an exceptional intermediate between mono- and dizygotic twinning. A spontaneously conceived twin pregnancy had monochorionic, diamniotic placentation from the 6 week ultrasound (US) (confirmed postnatally). From 14 weeks gestation, US showed phenotypic gender discordance in otherwise structurally normal twins with male (twin A) and female (twin B) phenotypes. FISH / SNP karyotyping on mid-trimester amniotic fluid showed twin A 50:50 XX/XY and twin B 90:10 XX/XY. Similar ratios were later confirmed in cord tissue. Genotyping indicated (i) maternally identical, sharing half their paternal genome, hence three-quarter identical or sesquizygotic twins (ii) parthenogenetic activation of the haploid oocyte as the initial step in the aetiology. Objective:-Describe the postnatal clinical and gonadal phenotype. Methods: Postnatal clinical and US assessments; FSH, AMH, Inhibin B levels; gonad biopsies with histopathology, immunohistochemistry and cytogenetics. Results: Postnatal assessments confirmed twin A to be phenotypically male and twin B female with accordant gender of rearing. The female had granulosa cell compromise suggested by FSH, AMH, Inhibin B at age 4.5 and 16 months. Bilateral intra-abdominal gonad biopsies at age 16 months showed dysgenesis with ovarian type stroma, abnormal primordial follicles and no seminiferous tubules. There were islands of cells, some cystic, with partly cribriform architecture, the largest consistent with gonadoblastoma. On immunohistochemistry, these islands of cells were positive for OCT-4, c-KIT, PLAP and Inhibin B. Ki-67 (proliferation marker) was positive in 2-10% of these cells. Cytogenetics (FISH) identified XY in 2.8-8.5% of cells, but confined to those islands of cells. The gonads were removed (no invasive germ cell tumour). The male had robust Sertoli cell markers at age 4.5mths. Bilateral intra-scrotal gonad biopsies at 25 months showed normal testes for age (OCT-4, c-KIT negative). Cytogenetics (FISH): 50% and 40% of cells XY in the gonads. Conclusions: This adds to the one prior report1 in which postnatal genotyping suggested sesquizygotic twins, 46,XX/46,XY but with phenotypic differences and no immunohistochemistry reported.L6279780992019-06-11 <br />