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46,XX male sex reversal syndrome is a rare genetic cause of male infertility. We report on two new cases of this syndrome in men presenting with hypogonadism and infertility. Cytogenetic and molecular analysis was performed in both patients. An extensive review of the literature for 46,XX male sex reversal syndrome cases related to infertility was also performed to fully characterise this syndrome. Genetic analyses showed translocation of the SRY on Xp chromosome and complete absence of all Azoospermia factor (AZF) genetic regions. All patients included in the review presented hypergonadotropic hypogonadism. Small testes were the most common clinical characteristic present in 90.2% of the patients, followed by small penis (31.8%), gynecomastia (26.8%) and poor hair distribution (15.4%). The presence of the SRY was identified in 130/154 (84.4%) patients: in 98.5% of cases, it was translocated on the Xp chromosome and in 1.5% on an autosome. All patients were azoospermic, due to the lack of AZF genetic regions. Males with normal phenotype and primary hypogonadism should be properly evaluated by the physicians and must be referred for cytogenetic and molecular analysis to exclude or confirm 46,XX male sex reversal syndrome. More cases of this syndrome with SRY translocated on an autosome are needed to identify if these patients have different characteristics than those with SRY translocated on Xp chromosome. Whole genome analysis of these patients is required to elucidate the genetic differences which are responsible for the phenotypic variability of the syndrome.

46,XX male sex reversal syndrome, or de la Chapelle syndrome, is a rare chromosomal abnormality related to male infertility. A 39-year-old male was referred for cytogenetic analysis because of primary hypogonadism and infertility. He had a normal male phenotype, mild gynecomastia and small testicles. Conventional cytogenetic analysis was performed on peripheral blood lymphocytes, and further investigation followed using molecular techniques. Karyotypic analysis showed a 46,XX karyotype in all metaphases examined. Polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques confirmed the presence of two X chromosomes and revealed the presence of the sex-determining region Y (SRY) gene on the short arm of one X chromosome, and the absence of all azoospermia factor (AZF) genetic regions. It is evident that men with primary hypogonadism and normal phenotype should undergo conventional cytogenetic analysis and, in the case of a 46,XX karyotype, further molecular testing should follow for the detection of the SRY gene. [ABSTRACT FROM AUTHOR]

The enthusiasms on 'intersex' have been with humanity since antique. Inadequacies in the management of the condition backwash in Psychosocial and medical morbidities with occasional mortality. The upsurge in the knowledge of its pathophysiology over generations has incredibly improved the management outcome. This study aims to present the fundamentals of the Pathophysiology and Management of DSD. The information provided is intended to guide in the basic evaluation and care of individuals with the disorder. Material and Method: Search from PubMed, EMBASE and AJOL for Literature on Disorders of Sexual development was reviewed. The search words were: intersex, the disorder of sexual differentiation (DSD), Pseudohermaphroditism, Hermaphroditism and Ambiguous genitalia. The literature on the Pathophysiology and the managementwas appraised and summarized. Conclusion: Genetic inquest and advances in molecular biology had provided cognizance on the pathophysiology of DSD. Patient's advocacy groups and de novo medical ethics necessitated the transformations in the approach to the management

A SRY-negative XX male describes a female karyotype with testicular tissue resulting from abnormal gonadal development. In such cases male gonad formation takes place in the absence of a Y chromosome which supports the hypothesis that some other genes are also responsible for testicular development. The present case report describes a one-year-old dog brought to the hospital with a complaint of no oestrus cycle. Apparently normal masculine bitch had an enlarged clitoris with an os on radiograph. A gonado-hysterectomy was performed. Instead of ovarian structures both testicular masses were present and a normal complete bicornuate uterus with a normal cervix was observed. The histology of both gonads showed two testes, each with its ductus deferens and the uterus with typical histological structure. Cytogenetic evaluation of peripheral blood lymphocytes revealed a female with a normal karyotype (78, XX). Polymerase chain reaction (PCR) analysis of genomic DNA showed that the SRY gene was absent.

A SRY-negative XX male describes a female karyotype with testicular tissue resulting from abnormal gonadal development. In such cases male gonad formation takes place in the absence of a Y chromosome which supports the hypothesis that some other genes are also responsible for testicular development. The present case report describes a one-year-old dog brought to the hospital with a complaint of no oestrus cycle. Apparently normal masculine bitch had an enlarged clitoris with an os on radiograph. A gonado-hysterectomy was performed. Instead of ovarian structures both testicular masses were present and a normal complete bicornuate uterus with a normal cervix was observed. The histology of both gonads showed two testes, each with its ductus deferens and the uterus with typical histological structure. Cytogenetic evaluation of peripheral blood lymphocytes revealed a female with a normal karyotype (78, XX). Polymerase chain reaction (PCR) analysis of genomic DNA showed that the SRY gene was absent. [ABSTRACT FROM AUTHOR]

Individuals with male phenotypes and 46 XX karyotype appear in about 1 of 20,000 births with clinical features varying from normal male appearance to sexual ambiguity and hermaphroditism. More than 80% of these patients present a spontaneous translocation of the SRY gene from the Y to the X chromosome in the paternal germinal cells. We present a case of a 2 years old boy diagnosed with minor hypospadias, bifid scrotum, normal penis and palpable gonads in the scrotum. The karyotype is 46 XX and FISH analysis reveals SRY translocation on one of the X chromosomes. Ultrasound exam does not reveal any mullerian structures and a hCG test proves the testes to be functional. A short course of treatment with hCG is recommended in order to induce the proper development of the scotal sac. The patient will need monitoring, in order to identify the development of hypergonadic hypogonadism, which characterizes such patients in later life. This case underlines the importance of comprehensively investigating any patient with even minor genitalia anomalies. [ABSTRACT FROM AUTHOR]

Purpose To evaluate hypotheses which explain phenotypic variability in sex determining region Ypositive 46,XX males. We investigate two 46,XX males without gonadal ambiguities. Methods Cytogenetic and molecular analyses were used to identify the presence of Y chromosome material and to map the translocation breakpoint. Finally, the pattern of X chromosome inactivation was studied using the methylation assay at the androgen receptor locus. Results The presence of Y chromosome material, including the sex determining region Y gene, was demonstrated in both men. However, the amount of translocated Y chromosome material differed between the patients. Different X chromosome inactivation patterns were found in the patients; random in one patient and non-random in the other. Conclusions We found a lack of association between phenotype and X chromosome inactivation pattern. Our cytogenetic and molecular analyses show support for the position effect hypothesis explaining the phenotypic variability in XX males. [ABSTRACT FROM AUTHOR]

Objective: To report a case of a 46,XX SRY-negative man with a male phenotype and azoospermia. Design: Case report. Setting: Molecular and Cytogenetic Unit in a University Hospital. Patient(s): A 35-year-old man with complete masculinization who referred to our institution because of a history of several years of infertility. Intervention(s): Lymphocytic karyotype and genetic counseling. Main outcome measure(s): Peripheral blood metaphases were analyzed by standard G-banding and Q-banding. Fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) analyses were performed. Result(s): Semen analysis showed azoospermia. Chromosome analysis revealed a 46,XX karyotype; molecular and cytogenetic analyses excluded the presence of SRY (the sex-determining region of the Y chromosome) gene. Conclusion(s): This case is one of the rare patients reported in the literature in whom testicular differentiation and a complete virilization in a 46,XX chromosomal constitution does not account for a translocation of the SRY gene to the X chromosome or to the autosomes. This finding suggests that other genes downstream from SRY, not yet identified, play an important role in sex determination. [Copyright &y& Elsevier]

Localization of the sex-determining region Y (SRY) was investigated in 2 XX males. Metaphase chromosomes from peripheral lymphocytes were stained by fluorescence in situ hybridization using DXZ1 and SRY probes. An identical hybridization signal with the SRY probe was found on an X chromosome in both cases. The karyotype of the 2 cases was 46,XX, t(X;Y)(p22.3;p11.3). It would appear that XX male is the presence of a Y-chromosome fragment transferred to the X-chromosome short arm by unequal interchange between homologous regions in the short arms of sex chromosomes. [ABSTRACT FROM AUTHOR]

The testicular histology and the presence or absence of 32 Y DNA loci was investigated, with a focus on the long arm of Y chromosome (Yq) interval 6, by means of a polymerase chain reaction strategy in 2 XX males. Seminiferous tubules lined by only Sertoli cells and a slight thickening of tubular walls were observed. The men showed an absence of 32 Y DNA loci. These facts suggest that severe spermatogenic impairment is caused by deletions of Yq interval 6 in XX males. [ABSTRACT FROM AUTHOR]

Ultrastructural study of testicular biopsy specimens from an XX male showed hyalinized seminiferous tubules and tubules containing only mature Sertoli cells. These cells possessed large lipid inclusions as well as microfilament bundles which were perpendicular to the basement membrane and parallel to one another. The basal lamina was thickened and composed of several parallel layers with myofibroblast layers between them. The interstitium showed nodular to diffuse Leydig cell hyperplasia. Four types of Leydig cells were found: 1) normal Leydig cells with crystals of Reinke; 2) cells with abundant microcrystalline inclusions as well as microfilaments and concentric cisternae of smooth endoplasmic reticulum; 3) vacuolated cells containing numerous large lipid droplets; 4) immature Leydig cells. The different ultrastructural abnormalities found in the Sertoli and Leydig cells might be considered as the histological expression of a tubular-interstitial dysgenesis which is reflected in the high levels of gonadotropins and low levels of testosterone. [ABSTRACT FROM AUTHOR]

The main factor influencing sex determination of an embryo is the sex-determining region Y (SRY\, a master regulatory gene located on the Y chromosome. The presence of SRY causes the bipotential gonad to differentiate into a testis. However, some individuals carry a Y chromosome but are phenotypically female (46.XY females) or have a female karyotype but are phenotypically male (46.XX males). 46, XX male is rare (1:20 000 in newborn males), and SRY positivity is responsible for this condition in approximately 90% of these subjects. External genitalia of 46.XX SRY-positive males appear as normal male external genitalia, and such cases are diagnosed when they present with small testes and/or infertility after puberty. Herein, we report an adolescent who presented with low testicular volume and who was diagnosed as a 46.XX male. SRY positivity was demonstrated in the patient by fluorescence in situ hybridization method. [ABSTRACT FROM AUTHOR]

Abstract: We report the case of a 2-year-old male with congenital symmetric facial diplegia, and bilateral paralysis of abduction of the eyes. Findings were compatible with a diagnosis of Möbius syndrome. Routine G-banded chromosome analysis revealed a mosaic karyotype with 40 cells showing normal 46,XX and 10 cells showing normal 46,XY. An XX male attributed to XX/XY mosaicism was diagnosed. The phenotype of our patient did not coincide with any described form of XX reversal syndrome, but and was a unique combination of both syndromes. The disorder of this patient is likely to represent a genetic condition with pleiotropic effects on brain development and sex determination, providing adding further evidence for the heterogeneity of Möbius syndrome and sex reversal syndromes. [Copyright &y& Elsevier]

46, XX male (de la Chapelle syndrome) is a rare syndrome with a frequency of 1 in 20,000–25,000 males. 46, XX males exist in different clinical categories with ambiguous genitalia or partially to fully mature male genitalia, in combination with complete or incomplete masculinisation. We herein report a case of SRY-negative XX male with complete masculinisation but with infertility, and co-existing with autoimmune thyroiditis. The patient had fully mature male genitalia with descended but small testes and no signs of undervirilisation. Peripheral blood culture for chromosome studies revealed 46 chromosomes with XX constitution. Repeat polymerase chain reaction analysis, using Y-specific sequence tagged sites analysing about 40 metaphases of genomic DNA, confirmed the absence of the Y chromosome, including any detectable SRY gene. We herein report a case of a man 46, XX male SRY with normal male phenotype and infertility. This case is the first reported case, co-existing with chronic autoimmune thyroiditis. [ABSTRACT FROM AUTHOR]

Prenatal diagnosis of sex differentiation disorders is extremely rare and is estimated in 1/2500 analyzed gestations. A group of this disorders are the 46, XX males and its incidence is estimated in 1/20000 male neonates. We report a male XX fetus in which the diagnosis of sex determination was requested at 20 gestation weeks to clarify the real gender of the fetus. Discrepancy between cytogenetic and ultrasonographic was detected. [ABSTRACT FROM AUTHOR]

Background: The XX male disorder of sex development (DSD) is a rare condition that is most commonly associated with the presence of the SRY gene on one of the X chromosomes due to unequal crossing-over between sex chromosomes during spermatogenesis. However, in about 20% of the XX male individuals, SRY is missing, although these persons have at least some testis differentiation. The genetic basis of genital ambiguity and the mechanisms triggering testis development in such patients remain unknown., Methods: The proband with 46,XX SRY -negative testicular DSD was screened for point mutations by whole exome sequencing and CNVs using a high-resolution DSD gene-targeted and whole genome array comparative genomic hybridisation. The identified Xp21.2 genomic alteration was further characterised by direct sequencing of the breakpoint junctions and bioinformatics analysis., Results: A unique, 80 kb microdeletion removing the regulatory sequences and the NR0B1 gene was detected by microarray analysis. This deletion disturbs the human-specific genomic architecture of the Xp21.2 dosage-sensitive sex (DSS) reversal region in the XX patient with male-appearing ambiguous genitalia and ovotestis., Conclusions: Duplication of the DSS region containing the MAGEB and NR0B1 genes has been implicated in testis repression and sex reversal. Identification of this microdeletion highlights the importance of genomic integrity in the regulation and interaction of sex determining genes during gonadal development., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To report a case of a 46,XX male with an insertion of the sex-determining region Y (SRY) region in the terminal end of the long arm of chromosome 16. Design: Case report. Setting: Molecular and cytogenetic units in a university hospital. Patient(s): An infertile male, with normal masculinization of the external genitalia, who was referred for chromosomal analysis as an unaffected member of a family with idiopathic hypertrophic osteoarthropathy. Intervention(s): Cytogenetic investigation, physical examination, and hormonal assays. Main Outcome Measure(s): Chromosomal analysis using GTG banding and fluorescence in situ hybridization (FISH). Result(s): Conventional chromosome analysis revealed a normal 46,XX karyotype. The FISH with bacterial artificial chromosomes (BACs) of the SRY region indicated the presence of this region on the terminal end of the long arm of chromosome 16. Conclusion(s): This is the first case of a 46,XX male with the SRY gene present on an autosome—here chromosome 16. The size of the inserted region containing SRY, inserted in 16qter, is approximately 600 kb. [Copyright &y& Elsevier]