XX Maleness and XX true hermaphroditism in SRY-negative monozygotic twins: additional evidence for a common origin

J Clin Endocrinol Metab. 2008 Feb;93(2):339-43. doi: 10.1210/jc.2007-1115. Epub 2007 Dec 4.


Context: Differentiation of testicular tissue in 46,XX individuals is seen either in XX males, the majority of them with SRY gene, or in individuals, usually SRY(-), with ovotesticular disorder of sex development (OT-DSD). Although they are sporadic cases, there are some reports on familial recurrence, including coexistence of XX maleness and OT-DSD in the same family.

Objective: We report on a case of SRY(-) 46,XX monozygotic twins with genital ambiguity.

Methods: Hormonal evaluation included testosterone, FSH, and LH measurements. SRY gene was investigated by PCR and two-step PCR in peripheral leukocytes and gonadal tissues, respectively. Direct DNA sequencing of the DAX-1 coding sequence was performed. Real-time PCR for SOX9 region on chromosome 17 was obtained.

Results: Both twins had a 46,XX karyotype. Twin A had a 1-cm phallus with chordee, penoscrotal hypospadias, and palpable gonads. Serum levels of FSH (2.34 mIU/ml), LH (8.8 mIU/ml), and testosterone (1.6 ng/ml) were normal, and biopsies revealed bilateral testes. Twin B had a 0.5-cm phallus, perineal hypospadias, no palpable gonad on the right, and a left inguinal hernia. Hormonal evaluation revealed high FSH (8.2 mIU/ml) and LH (15 mIU/ml) and low testosterone (0.12 ng/ml). Upon herniotomy, a right testis (crossed ectopia) and a small left ovotestis were found. SRY gene was absent in both peripheral leukocytes and gonadal tissue samples. Neither DAX-1 mutations nor SOX9 duplication was identified.

Conclusions: This case provides evidence that both XX maleness and XX OT-DSD are different manifestations of the same disorder of gonadal development.

Publication types

  • Case Reports

MeSH terms

  • Chromosome Aberrations
  • DAX-1 Orphan Nuclear Receptor
  • DNA / chemistry
  • DNA / genetics
  • DNA-Binding Proteins / genetics
  • Follicle Stimulating Hormone / blood
  • Genotype
  • Gonadal Dysgenesis, 46,XY / blood
  • Gonadal Dysgenesis, 46,XY / genetics*
  • Gonads / abnormalities*
  • High Mobility Group Proteins / genetics
  • Humans
  • Infant, Newborn
  • Luteinizing Hormone / blood
  • Male
  • Ovotesticular Disorders of Sex Development / blood
  • Ovotesticular Disorders of Sex Development / genetics*
  • Polymerase Chain Reaction
  • Receptors, Retinoic Acid / genetics
  • Repressor Proteins / genetics
  • SOX9 Transcription Factor
  • Sex-Determining Region Y Protein / genetics*
  • Testosterone / blood
  • Transcription Factors / genetics
  • Twins, Monozygotic / blood
  • Twins, Monozygotic / genetics*


  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • NR0B1 protein, human
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • SRY protein, human
  • Sex-Determining Region Y Protein
  • Transcription Factors
  • Testosterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • DNA