Human sexual differentiation is a highly complex process under the control of multiple genes and hormones. Abnormalities in normal sexual differentiation are relatively common and occur in approximately 1 per 4500 live births
8. Human males with a 46,XX karyotype were first described in 1964 by three different groups of investigators
9,10. The frequency of this syndrome has been estimated to be 1 in 20,000-25,000 newborn males, although there are considerable geographic variations
11. Molecular analyses have demonstrated that approximately 90% of patients with 46,XX karyotype carry a variable amount of Y material due to a Y-to-X interchange originated by an illegitimate recombination during paternal meiosis
12. In 1999, Kusz et al. demonstrated that in XX males with Y-to-X translocations, preferential inactivation of the Y-bearing X chromosome could be the major mechanism causing a sexually ambiguous phenotype
13. The origin of male phenotype in XX males could be the result of at least three different mechanisms: 1) translocation of Y sequences, including the SRY gene, to an X chromosome or to an autosome; 2) a mutation in a yet unknown X-linked or autosomal gene in the testis-determining pathway, and 3) cryptic Y chromosome mosaicism
14. XX males can be classified as Y-positive or Y-negative depending on the presence or absence of Y-derived specific sequences. Most 46,XX males fail to undergo normal pubertal development; axillary and body hair are generally scant, while pubic hair shows a female pattern of distribution. Gynecomastia occurs in approximately one third of cases and lack of spermatogenesis is always present. External genitalia are underdeveloped and the presence of small testes is a distinctive trait of the syndrome
11. In approximately 15% of XX males hypospadias, cryptorchidism, or severe genital ambiguity is observed
15. We detect presence of SRY gene in our patient (case 6) with male phenotype and 46,XX karyotype. It is a possible mechanism that this patient carry SRY gene due to X to Y translocation. Although it is now clear that the SRY gene plays a central role in triggering the formation of the testis from undifferentiated gonad, it has been suggested that other genes located either on the X or autosome may be involved in testicular differentiation
16,17.
There was no report of Y specific SRY sequence in female pseudohermaphrodites. We not detected Y chromosomal sequences in female hermaphrodites with 46,XX karyotype and ambiguous genitalia. Our study consistent with previous studies.
Al Agha were determined five syndromic child with ambigious genitalia. These were: Cardiogenital syndrome (2 cases); Denys–Drash syndrome (1 case); Miller-Dieker syndrome (1 case); and Klinefelter syndrome (1 case) 2. Of all 51 children, 12 (23.5%) had no definite final diagnoses 8. We determined one syndromic patient with ambigious genitalia and 47,XX,+18. These patients is determined syndromic cases.
Incomplete forms of AIS (PAIS) on the other hand rather present with an incomplete masculinization than a female phenotype and can have a varying range of internal male structures. Frequent features include phenotypic males with a penoscrotal hypospadias, often containing small testes. Additionally a small, blind-ending vaginal pouch without evidence of other female structures can be found. The clinical manifestation of all CAH forms is characterized by the virilization of the outer genitalia. It can be mild with a clitoral hypertrophy or a fusion of the posterior labial folds only, but also as severe as a male phenotype with bilateral undescended testes. On further examination, all patients with a regular karyotype of 46,XX have regular ovaries, Mullerian structures and regressed Mullerian duct syndrome, Wolfman ducts, since the missing SRY prevented the development of Sertoli cells and MIS, respectively 1. Our patients with AIS detected complete AIS syndrome phenotype and 14.3% incidence in all patients. Al Agha were determined 17.2% of ambigious patients 8.
The birth of a newborn with ambiguous genitalia frequently comes as a surprise for the parents, therapist. Although some authors report that 60% of affected children are diagnosed prenatally, many parents are faced with the situation at birth 1. Physical examination is key to diagnosis. Careful palpation to locate gonads at the genital folds or in the inguinal region provides the first element for diagnostic orientation. If gonads are absent, a diagnosis of female pseudohermap-hroditism seems advisable; if gonads are palpated, a diagnosis of male pseudohermaphroditism is more appropriate. Karyotyping is systematic while PCR analysis of the SRY gene provides information about the presence of a Y chromosome within 1 day 2. However, PCR based sex determination is rapid, reliable and economic and provides an accurate means of determining sex of an individual, including the detection of hidden Y sequence 18,19. The presence of a translocation of chromosomal material encoding the TDF from Y to X chromosome or to an autosome would explain testicular development in XX sex-reversed PCR techniques of eight 46,XX and eleven 46,XY patients with ambigious genitalia.
In conclusion, medical management of XX males includes androgen replacement when needed, psychologic orientation to prevent abnormal social and sexual behavior in cases of impaired body image, and reconstructive surgery as soon as the diagnosis is established in individuals with genital ambiguity. Unfortunately, in our retrospective study provides no information concerning the outcomes of psychological and sexual function following the initial decision of sex of rearing. The etiology of ambiguous genitalia is variable. The physician managing these families could minimize the trauma of having a child with unidentified sex by providing appropriate genetic counseling so that the parents can make an early decision. Prenatal DNA testing in at-risk families should be considered and appropriate therapy offered to minimize or prevent genital ambiguity.
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