A case of true hermaphroditism reveals an unusual mechanism of twinning

Abstract

Traditionally twins are classified as dizygous or fraternal and monozygous or identical (Hall Twinning, 362, 2003 and 735-743). We report a rare case of 46,XX/46,XY twins: Twin A presented with ambiguous genitalia and Twin B was a phenotypically normal male. These twins demonstrate a third, previously unreported mechanism for twinning. The twins underwent initial investigation with 17-hydroxyprogesterone and testosterone levels, pelvic ultrasound and diagnostic laparoscopy. Cytogenetic analysis was performed on peripheral blood cells and skin fibroblasts. Histological examination and Fluorescence in situ hybridization studies on touch imprints were performed on gonadal biopsies. DNA analysis using more than 6,000 DNA markers was performed on skin fibroblast samples from the twins and on peripheral blood samples from both parents. Twin A was determined to be a true hermaphrodite and Twin B an apparently normal male. Both twins had a 46,XX/46,XY chromosome complement in peripheral lymphocytes, skin fibroblasts, and gonadal biopsies. The proportion of XX to XY cells varied between the twins and the tissues evaluated. Most significantly the twins shared 100% of maternal alleles and approximately 50% of paternal alleles in DNA analysis of skin fibroblasts. The twins are chimeric and share a single genetic contribution from their mother but have two genetic contributions from their father thus supporting the existence of a third, previously unreported type of twinning.

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

“…(2) Parthenogenetic activation and cleavage of the ovum would result in identical maternal genomic contribution if both parthenogenetic components are fertilized. This is one possible explanation for a pair of opposite-sexed discordant chimeric twins, one of whom is a true hermaphrodite [Souter et al, 2007] (Fig. 4).…”

“…4). In the pair reported by Souter et al, 2007, the twins (spontaneously conceived, but of unknown chorionicity) were assigned opposite genders, and both twins had 46,XX and 46,XY cell lines in peripheral blood and skin fibroblasts, as well as XX, XY and X cells found by FISH in touch preparations from gonads of both twins. DNA markers and SNPs showed that both twins had inherited the same informative maternal alleles and SNPs (100%), and 52% of same paternal SNPs.…”

“…(3) Dispermic fertilization followed by diploidization of the triploid zygote [Golubovsky, 2003] is another possible explanation for the twins described by Souter et al [2007]. In this mechanism, two cell lines emerge from the dispermic triploid zygote; one cell line has extruded one male (X-bearing) pronucleus, whereas the other cell line has extruded the other male (Y-bearing) pronucleus.…”

Heterokaryotypic Pregnancy: Monozygotic Monochorionic Twins Discordant for Trisomy 13

“…As expected, initial zygosity studies demonstrated monozygosity; however, subsequent molecular studies from skin fibroblasts diagnosed dizygosity. The authors hypothesized three probable mechanisms to explain their findings: (1) fusion of the chorions at early stages of development with subsequent degeneration of the fused chorion within the dividing membrane, (2) fusion of the trophoblasts before implantation with subsequent development of distinct inner cellular masses and (3) double fertilization of the meiotic products of a single oocyte with two sperms [19,20] .…”

Blood Chimerism in a Dizygotic Dichorionic Pregnancy

“…This is a rare case of blood chimerism in dichorionic placentas, in contrast to those in monochorionic placentas. [2], or normal males [3]. Individuals with blood chimerism show no abnormality in relation to sexual development [4][5][6].…”