A possible common origin of ?Y-negative? human XX males and XX true hermaphrodites

Abstract

We have studied nine patients aged 1 month to 16 years with 46, XX karyotypes and testicular tissue. Some of these patients were followed through puberty. Phenotypically, two presented normal and seven abnormal external genitalia (AG). Among this latter group, four showed hypospadias and three true hermaphroditism (TH). The endocrine data were similar in all three groups: testosterone levels were within normal limits during puberty, decreasing in adulthood; gonadotrophin levels were above the control values at mid puberty. Histologies of the two sub groups of AG patients were identical up to 5 years of age and presented differences when compared with controls, regardless of the ovarian part of the ovotestis. However, in patients older than 8 years, germ cells disappeared and dysgenesis became obvious. In one patient, the ovarian zone of the gonad was detected only after complete serial sections of the removed gonad were examined. Southern blot analysis with Y-DNA probes displayed Y-specific material for the classic 46 XX males and a lack of such sequences for all patients with AG and TH. Based on these findings, we postulate that 46, XX males with AG and 46, XX TH may represent alternative manifestations of the same genetic defect. These data together with those concerning familial cases of 46, XX males with AG and 46, XX TH suggest an autosomally (or pseudoautosomally) determined mechanism.

Clinical, cytogenetic, and molecular analysis with 46,XX male sex reversal syndrome: case reports

“…46,XX male syndrome is rare and its incidence is about 1:20000 in newborn males [2]. As far as the sexual phenotype is concerned, three clinical categories of sex-reversed 46,XX individuals have been identified: (1) Classic XX males, infertility with normal male internal and external genitalia; (2) XX males with ambiguous genitalia, usually detected at birth by external genital ambiguities such as hypospadias, micropenis, or hyperclitoridy; (3) XX true hermaphrodites, who carry internal or external genital ambiguities detected at birth [3][4][5].…”

Homem XX: relato de três casos na faixa etária pediátrica

“…O paciente 2 apresentava genitália ambígua; pode-se supor, portanto, que faça parte do espectro que inclui os hermafroditas verdadeiros 46,XX SRY-negativos (2). O paciente 3, por sua vez, apresentava ginecomastia, Em 1987, De La Chapelle aventou várias hipóteses para explicar a presença de testículos em homens XX na ausência do cromossomo Y: a existên-cia de um pequeno fragmento de Y capaz de promover a determinação testicular que não seria detectado pelas técnicas empregadas até então ou a ocorrência de determinação testicular por outros mecanismos que não incluiriam a ação do então chamado fator de diferenciação testicular (TDF).…”

Xx-Male Syndrome Bearing the Sex-Determining Region Y

“…Indeed, most of the cases that were suspected of being XX-males were found to possess SRY, but not all XX-male patients have SRY. Infantile patients who were mostly found with congenital anomalies such as hypospadias or undescended testicles were especially inclined to be lacking this region [1,8,13].…”

“…Alternative pathways may therefore be possible even if SRY itself is not evident. The other explanations include chromosomal mosaicism [2] and mutation of an autosomal (or pseudoautosomal) gene [1]. Dislocation of SRY in positive cases is supposed to be the result of an interchange between X and Y chromosomes during paternal meiosis.…”

“…Abbas analyzed 6 XX-male cases as well as 3 true hermaphrodites [1]. Two cases without hypospadia were both positive for SRY, whereas all of 4 hypospadic cases were negative.…”