XX Maleness and XX true hermaphroditism in SRY-negative monozygotic twins: additional evidence for a common origin.
BACKGROUND
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.
Grupo Interdisciplinar de Estudos da Determinação e Diferenciação do Sexo, Faculdade de Ciências Médicas, UNICAMP, 13083-970 Campinas, São Paulo, Brasil. atmg@fcm.unicamp.br
Andréa Trevas
AT
Maciel-Guerra
Maricilda Palandi
MP
de Mello
Fernanda Boechers
FB
Coeli
Marcelo Lima
ML
Ribeiro
Márcio Lopes
ML
Miranda
Antonia Paula
AP
Marques-de-Faria
Maria Tereza Matias
MT
Baptista
Suzana Guimarães
SG
Moraes
Gil
G
Guerra-Júnior
D002869:Chromosome Aberrations; D057137:DAX-1 Orphan Nuclear Receptor; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D006061:Gonadal Dysgenesis, 46,XY / Q000097:blood / Q000235:genetics*; D006066:Gonads / Q000002:abnormalities*; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D050090:Ovotesticular Disorders of Sex Development / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein / Q000235:genetics*; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000235:genetics; D014430:Twins, Monozygotic / Q000097:blood / Q000235:genetics*
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA