A case of true hermaphroditism reveals an unusual mechanism of twinning


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.

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  1. Benirschke K (1970) Spontaneous chimerism in mammals A critical review. Curr Top Pathol 51:1–61

    Google Scholar 

  2. Boklage CE (1987) The organization of the oocyte and embryogenesis in twinning and fusion malformations. Acta Genet Med Gemellol 36:421–431

    PubMed  CAS  Google Scholar 

  3. Dewald G, Haymond MW, Spurbeck JL, Moore SB (1980) Origins of chi46,XX/46,XY chimerism in a human true hermaphrodite. Science 207:321–323

    PubMed  Article  CAS  Google Scholar 

  4. Giltay JC, Brunt T, Beemer FA, Wit JM, Ploos van Amstel HK, Pearson PL, Wijmenga C (1998) Polymorphc detection of a parthenogenetic maternal and double paternal contribution to a 46,XX/46,XY hermaphrodite. Am J Hum Genet 62:937–940

    PubMed  Article  CAS  Google Scholar 

  5. Golubovsky MD (2003) Postzygotic diploidization of triploids as a source of unusual cases of mosaicism, chimerism and twinning. Hum Reprod 18:236–242

    PubMed  Article  CAS  Google Scholar 

  6. Hall JG (2003) Twinning. Lancet 362:735–743

    PubMed  Article  Google Scholar 

  7. Haseman JK, Elston RC (1972) The investigation of linkage between a quantitative trait and a marker locus. Behav Genet 2:3–19

    PubMed  Article  CAS  Google Scholar 

  8. Hughes IA, Houk C, Ahmed SF, Lee PA (2006) Consensus statement on management of intersex disorders. Arch Dis Child 91(7):554–563

    PubMed  Article  CAS  Google Scholar 

  9. Krob G, Braun A, Kuhnle U (1994) True hermaphroditism: geographical distribution, clinical findings, chromosomes and gonadal histology. Eur J Pediatr 153:2–10

    PubMed  Article  CAS  Google Scholar 

  10. Murray SS, Oliphant A, Shen R, McBride C, Steeke RJ, Shannon SG, Rubano T, Kermani BG, Fan JB, Chee MS, Hansen MS (2004) A highly informative SNP linkage panel for human genetic studies. Nat Methods 1:113–117

    PubMed  Article  CAS  Google Scholar 

  11. Niu DM, Pan CC, Lin CY, Hwang BT, Chung MY (2002) Mosaic or chimera? Revisiting an old hypothesis about the cause of the 46,XX/46,XY hermaphrodite. J Pediatr 140:732–735

    PubMed  Article  Google Scholar 

  12. Repas-Humpe LM, Humpe A, Lynen R, Glock B, Dauber EM, Simson G, Mayr WR, Kohler M, Ever S (1999) A dispermic chimerism in a 2 year–old Caucasian boy. Ann Hematol 78:431–434

    PubMed  Article  CAS  Google Scholar 

  13. Strain L, Warner JP, Johnston T, Bonthron DT (1995) A human parthenogenetic chimaera. Nat Genet 11(2):154–159

    Article  Google Scholar 

  14. Strain L, Dean JCS, Hamilton MPR, Bonthron DT (1998) A true hermaphrodite chimera resulting from embryo amalgamation after in vitro fertilization. N Engl J Med 338:166–169

    PubMed  Article  CAS  Google Scholar 

  15. Uehara S, Nata M, Nagae M, Sagisaka K, Okamura K, Yajima A (1995) Molecular biologic analysis of tetragametic chimerism in a true hermaphrodite with 46,XX/46,XY. Fertil Steril 63:189–192

    PubMed  CAS  Google Scholar 

  16. Van Dijk BA, Boomsma DI, de Man AJ (1996) Blood chimerism in human multiple births is not rare. Am J Med Genet 61:264–268

    PubMed  Article  Google Scholar 

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This study was supported by grants to GWM from the National Health and Medical Research Council of Australia (159100, 339446).

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Correspondence to Vivienne L. Souter.

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Souter, V.L., Parisi, M.A., Nyholt, D.R. et al. A case of true hermaphroditism reveals an unusual mechanism of twinning. Hum Genet 121, 179–185 (2007). https://doi.org/10.1007/s00439-006-0279-x

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  • Skin Fibroblast
  • Seminiferous Tubule
  • Touch Imprint
  • True Hermaphroditism
  • True Hermaphrodite