Endocrine Abstracts

JOINT1426

Background: We present the case of a newborn child with prenatal diagnosis of 46,XY karyotype in non-invasive prenatal testing (NIPT) in two tests in combination with a female internal and external genital phenotype in prenatal ultrasound.

Case Presentation: The child was born at term with a birth weight of 3575g and a length of 50cm. External genitalia were unremarkably female without virilisation or malformations. On postnatal ultrasound, the internal genitalia showed a uterus. However, gonads could not be identified with certainty. The postnatal karyotype from blood lymphocytes showed a 46,XX(2)/46,XY(18) chimerism. A second postnatal karyotype from oral mucosa showed a 46,XY karyotype in all cells analyzed. A plasma steroid analysis obtained at the age of 3 months during the so-called ‘mini puberty’, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), showed testosterone and estradiol levels below the lower limit of detection (< 0.02 nmol/l[reference: 0.1-0.7) and <5 pmol/l[10-193], respectively). However, laboratory analysis showed significantly elevated Anti-Müllerian hormone (AMH) and Inhibin B levels for female gender (21 ng/ml [0.08-8.9] and 210 pg/ml [4.8-83], respectively), which could be interpreted as confirmation of the presence of Sertoli cells and thus the presence of male gonadal differentiation.

Conclusions: In a newborn child with undoubtedly female external genitalia, karyotype from peripheral blood showed a chromosomal 46,XX/46,XY chimerism, whereas the karyotype from oral mucosa did not. When interpreting this, we must take into account that cell mosaics may have a different expression in different tissues. Elevated levels of AMH and Inhibin B indicate testicular gonadal differentiation. However, this is currently in contradiction with the presence of a uterus on ultrasound. The absence of testosterone is consistent with female external genital differentiation. As estradiol is not detectable by a highly sensitive LC-MS/MS method, we have no information on possible ovarian differentiation of the gonads. As only 2 out of 20 cells in the peripheral blood showed the 46,XX constellation, we also initiated array-CGH analysis and exome sequencing. Finally, a minimally invasive gonadal biopsy should be performed to assess the presence of ovotestes and the risk of gonadal tumor development. Medical care will be provided throughout childhood and adolescence, including hormone therapy if necessary and counselling on gender identity issues.