Ventral-Onlay Buccal Mucosal Graft Urethroplasty of a Perineal Fistula in a 26-Year-Old Patient With 46 XX Male Syndrome: A Case Report.

Substitution urethroplasty with either a flap or graft is the gold standard for treating long segment urethral strictures. In 1992, Burger and colleagues rediscovered and popularized buccal mucosal graft (BMG). After that El-Kassaby and colleagues, in 1993, used BMG to repair anterior urethral stricture. De la Chapelle syndrome or 46 XX male syndrome is a rare genetic disorder found in 1 in 20,000-25,000 men. This condition described as a presentation of male phenotype along a 46 xx karyotype. In this case report, we report a reconstructive surgery of a 46 XX male syndrome with ambiguous genitalia who presented with the chief complaint of bulbar urethral fistula opened in the perineal space. In this case, we used a buccal mucous graft with the ventral-onlay urethroplasty technique for reconstructing the failed bulbar urethra and closure of the fistula.

An azoospermic male with a novel chromosome 46, XX, der(15)t(Y; 15)(p11.3; p12).

Male individuals with a 46, XX karyotype are commonly diagnosed with 46, XX male sex reversal syndrome, one of the rarest sex chromosomal anomalies. In this case, we report a rare XX male with Y-specific DNA sequences located near the end of chromosome 15 p-arm, which was verified by fluorescent in situ hybridization (FISH) as well as copy number variation sequencing (CNV-seq) based on the next- generation sequencing method (>100 Kb). To the best of our knowledge, there have been no reports of XX male with the Yp region transferred to the terminal of chromosome 15 short arm.

Identification of an SRY-negative 46,XX infertility male with a heterozygous deletion downstream of SOX3 gene.

BACKGROUND: A male individual with a karyotype of 46,XX is very rare. We explored the genetic aetiology of an infertility male with a kayrotype of 46,XX and SRY negative. METHODS: The peripheral blood sample was collected from the patient and subjected to a few genetic testing, including chromosomal karyotyping, azoospermia factor (AZF) deletion, short tandem repeat (STR) analysis for AMELX, AMELY and SRY, fluorescence in situ hybridization (FISH) with specific probes for CSP 18/CSP X/CSP Y/SRY, chromosomal microarray analysis (CMA) for genomic copy number variations(CNVs), whole-genome analysis(WGA) for genomic SNV&InDel mutation, and X chromosome inactivation (XCI) analysis. RESULTS: The patient had a karyotype of 46,XX. AZF analysis showed that he missed the AZF region (including a, b and c) and SRY gene. STR assay revealed he possessed the AMELX in the X chromosome, but he had no the AMELY and SRY in the Y chromosome. FISH analysis with CSP X/CSP Y/SRY showed only two X centromeric signals, but none Y chromosome and SRY. The above results of the karyotype, FISH and STR analysis did not suggest a Y chromosome chimerism existed in the patient's peripheral blood. The result of the CMA indicated a heterozygous deletion with an approximate size of 867 kb in Xq27.1 (hg19: chrX: 138,612,879-139,480,163 bp), located at 104 kb downstream of SOX3 gene, including F9, CXorf66, MCF2 and ATP11C. WGA also displayed the above deletion fragment but did not present known pathogenic or likely pathogenic SNV&InDel mutation responsible for sex determination and development. XCI assay showed that he had about 75% of the X chromosome inactivated. CONCLUSIONS: Although the pathogenicity of 46,XX male patients with SRY negative remains unclear, SOX3 expression of the acquired function may be associated with partial testis differentiation of these patients. Therefore, the CNVs analysis of the SOX3 gene and its regulatory region should be performed routinely for these patients.

The importance of genetic research in cases of severe male factor infertility: A case of 46,XX testicular disorder of sex development.

46,XX testicular disorder of sex development is a rare syndrome characterized by an inconsistency between genotype and phenotype. Affected individuals present variant genitalia between male and ambiguous, non-functional testicles, non-obstructive azoospermia, generally accompanied by hypergonadotropic hypogonadism, a condition known for high levels of gonadotrophic hormones. In some cases, disorders of sexual development are diagnosed during puberty. However, a significant number of individuals show physical characteristics common to males that are not clinically suspicious. As a result, patients with the condition may remain undiagnosed. Many individuals with the condition are diagnosed as adults, due to infertility. The present study discusses the case of an individual who underwent karyotyping for sterility and was found to be a 46,XX male. Despite having a female karyotype, the presence of the sex-determining region Y gene explains the manifestation of masculine secondary sex characteristics. This report highlights the importance of genetic evaluation, considering that carriers may present significant complications resulting from the disorder. Based on correct diagnosis, it is possible to improve a carrier's quality of life through multidisciplinary approaches and help them achieve pregnancy through assisted reproductive technology treatments.

46,XX male syndrome with mullerianosis of the urinary bladder: A new clinical entity.

Müllerianosis of the urinary bladder is a rare entity characterized by the presence of an admixture of at least two types of müllerian tissue in the muscularis propria of the bladder. We report the case of a 43-year-old male patient presented for urological evaluation due to episodes of total gross hematuria. Physical examination revealed ambiguous external genitalia. Abdomiopelvic CT scan revealed a tumor at the level of the bladder floor. Transurethral resection of the bladder lesions was done and histopathological studie confirmed the diagnosis of müllerianosis. Karyotype analysis showed a 46 XX male syndrome.

Multiscale analysis of SRY-positive 46,XX testicular disorder of sex development: Presentation of nine cases.

46,XX testicular disorder of sex development (46,XX TDSD) is a relatively rare condition characterised by the presence of testicular tissue with 46,XX karyotype. The present study aims to reveal the phenotype to genotype correlation in a series of sex-determining region Y (SRY)-positive 46,XX TDSD cases. We present the clinical findings, hormone profiles and genetic test results of six patients with SRY-positive 46,XX TDSD and give the details and follow-up findings of our three of previously published patients. All patients presented common characteristics such as azoospermia, hypergonadotropic hypogonadism and an SRY gene translocated on the terminal part of the short arm of one of the X chromosomes. Mean ± standard deviation (SD) height of the patients was 164.78 ± 8.0 cm. Five patients had decreased secondary sexual characteristics, and three patients had gynaecomastia with varying degrees. Five of the seven patients revealed a translocation between protein kinase X (PRKX) and inverted protein kinase Y (PRKY) genes, and the remaining two patients showed a translocation between the pseudoautosomal region 1 (PAR1) of X chromosome and the differential region of Y chromosome. X chromosome inactivation (XCI) analysis results demonstrated random and skewed XCI in 5 cases and 1 case, respectively. In brief, we delineate the phenotypic spectrum of patients with SRY-positive 46,XX TDSD and the underlying mechanisms of Xp;Yp translocations.

[Syndrome Of 46, XX Male With Sex-Determining Region Of Y (SRY) Chromosome Missing, Bilateral Gynecomastia And Complete Virilization: About A Case]. / Le Syndrome Du 46, XX Male Avec Absence Du Gene Sex-Determining Region Of Y (SRY) Chromosome, A Propos D'un Cas.

Absent SRY gonadal dysgenesis (negative) is the set of clinical and biological manifestations linked to the lack of development of the testes in humans. Authors report the first case of gonadal dysgenesis SRY-negative 46, XX male with gynecomastia documented in Mali. CASE OBSERVATION: This is a 15 years old boy of a deaf-mute brother, no family consanguinity. He was referred to the hospital because of severe bilateral gynecomastia. Hypergonado-tropic hypogonadism condition was investigated by hormonal laboratory assessment and the result of cytogenetic analysis carried out in France revealed a karyotype SRY-negative 46, XX isch Yp11, 3. The patient received psychological assistance and substitutive treatment based on testosterone. Reconstructive surgery was also conducted to correct urogenital malformations. CONCLUSION: Diagnosis of 46, XX male syndrome is rare and need cytogenetic analysis. In Mali, cost and availability of this technique make diagnosis difficult and care inadequate for patients.

La dysgénésie gonadique à SRY absent (négatif) est l'ensemble des manifestations clinico-biologiques liées à l'absence de développement des testicules chez l'homme. Les auteurs rapportent le premier cas de dysgénésie gonadique type 46, XX male à SRY Négative avec gynécomastie documenté au Mali. OBSERVATION: Il s'agissait d'un jeune garçon de 15 ans, avec antécédents d'un frère sourd-muet, sans consanguinité familiale, qui a consulté pour gynécomastie bilatérale marquée. Devant l'hypogonadisme hypergonadotrope objectivé sur le bilan hormonal, une étude cytogénétique réalisée en France a montré un caryotype à 46, XX isch Yp 11,3 à SRY Négative. La prise en charge repose sur une assistance psychologique, le traitement substitutif en testostérone et la chirurgie réparatrice des malformations uro-génitales. CONCLUSION: Le diagnostic du syndrome 46, XX mâle est rare et le diagnostic est cytogénétique. Le coût et l'accessibilité de cette technique au Mali rendent le diagnostic difficile et la prise en charge inefficiente.

Molecular cytogenetic analysis and genetic counseling: a case report of eight 46,XX males and a literature review.

BACKGROUND: 46,XX male syndrome is a rare disorder that usually causes infertility. This study was established to identify the genetic causes of this condition in a series of 46,XX males through the combined application of cytogenetic and molecular genetic techniques. CASE PRESENTATION: We identified eight azoospermic 46,XX males who underwent infertility-related consultations at our center. They all presented normal male phenotypes. In seven of the eight 46,XX males (87.5%), translocation of the SRY gene to the terminal short arm of the X chromosome was clearly involved in their condition, which illustrated that this translocation is the main mechanism of 46,XX sex reversal, in line with previous reports. However, one patient presented a homozygous DAX1 mutation (c.498G > A, p.R166R), which was not previously reported in SRY-negative XX males. CONCLUSIONS: We proposed that this synonymous DAX1 mutation in case 8 might not be associated with the activation of the male sex-determining pathway, and the male phenotype in this case might be regulated by some unidentified genetic or environmental factors. Hence, the detection of genetic variations associated with sex reversal in critical sex-determining genes should be recommended for SRY-negative XX males. Only after comprehensive cytogenetic and molecular genetic analyses can genetic counseling be offered to 46,XX males.

46 XX male syndrome with hypogonadotropic hypogonadism: A case report.

We report a 46 XX male syndrome diagnosed after failure of gonadotropin therapy taken for hypogonadotropic hypogonadism due to a pituitary macroadenoma. A 39-year-old man with a non-functioning pituitary macroadenoma was admitted to our clinic due to vision loss and infertility. After pituitary surgery, vision loss improved while infertility still existed. Low testosterone levels without elevated gonadotropins were established suggesting hypogonadotropic hypogonadism due to pituitary adenoma. Gonadotropin treatment was initiated. There was no response to treatment after 12 months. A karyotype analysis was ordered to investigate other causes of infertility. Karyotype analysis showed a 46 XX male syndrome that can explain the failure of gonadotropin therapy. Testosterone therapy was started instead of gonadotropin therapy. 46 XX male syndrome usually presents with hypergonadotropic hypogonadism. However, in our case, it presented with hypogonadotropic hypogonadism due to pituitary mass not responding to gonadotropin therapy. It is important to keep in mind to obtain a genetic analysis of patients whose gonadotropin therapy failed, even if their gonadotropin levels are not elevated.

Patient with Disorders of Sex Development (DSD): A Case Report from a Tertiary Care Hospital in Thiruvananthapuram, India.

BACKGROUND: 46 XX male syndrome, a rare case of infertility was first reported by de la Chapelle in 1964. In newborn males, the incidence rate of the syndrome varies from 1/9000 to 1/20000. Here, a case of 46 XX male syndrome is reported with clinical, biochemical and genetic changes of the patient and normal masculine features. CASE PRESENTATION: A 29 year old male with infertility registered at the Sree Avittom Thirunal Hospital of Government Medical College, Thiruvananthapuram for fertility treatment. He was diagnosed with non obstructive azoospermia in repeated semen analysis. Chromosomal analysis on peripheral blood lymphocytes has revealed 46 XX male syndrome and the result was confirmed with Fluorescent In situ Hybridization (FISH). Real time polymerase chain reaction failed to detect genes on azoospermia factor regions, AZFa, AZFb and AZFc of Y chromosome, but detected SRY gene positivity. Masculine features of patient were normal except small sized testis, ejaculatory dysfunction and azoospermia. CONCLUSION: Appearance of the external genitalia will be generally normal in 46 XX with SRY positive males and generally difficult to identify before puberty because there will not be any significant clinical indication. The present case report demonstrates that mere physical or clinical examination may not disclose the genetic defects. Therefore, in addition to general examination, it is essential to perform genetic analysis on men with infertility.

Análisis clínico y citogenético de un caso de trastorno del desarrollo sexual testicular XX con SRY negativo / Clinical and Cytogenetic Analysis of a Case of SRY-Negative XX Testicular Disorder of Sex Development / Análise clínica e citogenética de um caso de transtorno do desenvolvimento sexual testicular XX com SRY-negativo

Resumen: El trastorno del desarrollo sexual (TDS) testicular XX es una patología que se presenta en un individuo con cariotipo 46,XX con un fenotipo anatómico de genitales externos masculinos, que pueden variar desde la normalidad hasta la ambigüedad genital. Clínicamente se han descrito dos subgrupos de hombres 46,XX con SRY-negativos y SRY-positivos, dependiendo de la presencia o no del gen SRY que normalmente se encuentra en el cromosoma Y participando en la determinación testicular. En este artículo se describen los antecedentes personales y los hallazgos clínicos de un infante con anomalías del meato urinario en el cual se identificó un complemento cromosómico 46,XX. También, se realizó hibridación in situ fluorescente en linfocitos de sangre periférica que demostró la ausencia del gen SRY y confirmó la presencia de dos cromosomas X.

Abstract XX testicular disorder of sex development (DSD) is a pathology that occurs in an individual with a 46,XX karyotype and an anatomical phenotype of male external genitalia, which may vary from normal to ambiguous. Clinically, two subgroups of SRY-negative and SRY-positive, 46, XX men have been described, depending on the presence of the SRY gene that is normally found on the Y chromosome participating in testicular determination. This article describes the personal history and clinical findings of an infant with urethral meatus abnormalities in whom a 46,XX chromosome set was identified. Also, fluorescent in situ hybridization was performed in peripheral blood lymphocytes which demonstrated the absence of the SRY gene and confirmed the presence of two X chromosomes.

Resumo: O transtorno do desenvolvimento sexual (TDS) testicular XX é uma patologia apresentada em um indivíduo com cariótipo 46,XX com um fenótipo anatômico de genitais externos masculinos, que podem variar da normalidade à ambiguidade genital. Clinicamente, são descritos dois subgrupos de homens 46,XX com SRY-negativos e SRY-positivos, dependendo da presença ou não do gene SRY que normalmente se encontra em Y cromossomo participando da determinação testicular. Neste artigo, são descritos os antecedentes pessoais e os achados clínicos de uma criança com anomalias de meato urinário em que foi identificado um complemento cromossômico 46,XX. Além disso, foi rea -lizada hibridação in situ fluorescente em linfócitos de sangue periférico que demonstrou a ausência do gene SRY e confirmou a presença de dois cromossomos X.

[Genetic analysis of a case of 46, XX, SRY－ male syndrome].

OBJECTIVE: To identify the etiology of chromosome abnormality in an infertile man and analyze the correlation between the genotype and phenotype. METHODS: We analyzed the karyotype of an infertile male using the routine G-banding technique and then the chromosome abnormality of the patient by Illumina Human CytoSNP-12 Beadchip array. RESULTS: Negative results were found in the examination of the sex-determining region Y (SRY) gene and the STR locus in the AZF zone of the patient. The karyotype of the patient was 46, XX. SNP array showed a 1.05 Mb 19p12 duplication and a 0.93 Mb Xq27.1 duplication. CONCLUSIONS: The patient was confirmed as a case of 46,XX male syndrome. The increased copies of the FGF13 gene may be the major causes of abnormal sex determination and testis development.

Genetic analysis of a case of 46, XX, SRY－ male syndrome / 中华男科学杂志

<p><b>Objective</b>To identify the etiology of chromosome abnormality in an infertile man and analyze the correlation between the genotype and phenotype.</p><p><b>METHODS</b>We analyzed the karyotype of an infertile male using the routine G-banding technique and then the chromosome abnormality of the patient by Illumina Human CytoSNP-12 Beadchip array.</p><p><b>RESULTS</b>Negative results were found in the examination of the sex-determining region Y (SRY) gene and the STR locus in the AZF zone of the patient. The karyotype of the patient was 46, XX. SNP array showed a 1.05 Mb 19p12 duplication and a 0.93 Mb Xq27.1 duplication.</p><p><b>CONCLUSIONS</b>The patient was confirmed as a case of 46,XX male syndrome. The increased copies of the FGF13 gene may be the major causes of abnormal sex determination and testis development.</p>

A young male adolescent with feminine appearance: diagnosis of 46, XX syndrome neglected for 4 years with gynaecomastia presentation.

Gynaecomastia is common in infancy and adolescent boys, but other inciting causes should be kept in mind and necessitate further evaluation should be conducted to determine any underlying conditions. A 22-year-old unmarried male adolescent visited our endocrinology clinic for feminine appearance despite operations for bilateral gynaecomastia 4 years ago. Physical examination showed inverted triangular distribution of pubic hair, sparse beard, small-sized testes, flaccid short penis and surgical scar of the chest wall. Serum hormones study revealed primary hypergonadotropic hypogonadism, and cytogenetic study disclosed female complement (46, XX). The authors recommend that sexual chromosome abnormality should be considered in patients with hypogonadism to avert androgen deficiency-related complications early and that long-term team care should be provided to improve the patient's health-related quality of life.

A rare case of 46, XX SRY-negative male with approximately 74-kb duplication in a region upstream of SOX9.

The 46, XX male disorder of sex development (DSD) is a rare genetic condition. Here, we report the case of a 46, XX SRY-negative male with complete masculinization. The coding region and exon/intron boundaries of the DAX1, SOX9 and RSPO1 genes were sequenced, and no mutations were detected. Using whole genome array analysis and real-time PCR, we identified a approximately 74-kb duplication in a region approximately 510-584 kb upstream of SOX9 (chr17:69,533,305-69,606,825, hg19). Combined with the results of previous studies, the minimum critical region associated with gonadal development is a 67-kb region located 584-517 kb upstream of SOX9. The amplification of this region might lead to SOX9 overexpression, causing female-to-male sex reversal. Gonadal-specific enhancers in the region upstream of SOX9 may activate the SOX9 expression through long-range regulation, thus triggering testicular differentiation.

Male genitoplasty for 46 XX congenital adrenal hyperplasia patients presenting late and reared as males.

AIM: To evaluate the clinical profile and management of 46 XX Congenital Adrenal Hyperplasia (CAH) patients presenting with severe virilization and assigned a male gender. MATERIALS AND METHODS: Of 173 children diagnosed with CAH at the Pediatric Intersex Clinic since 1980, seven children with CAH presented late with severe virilization and were reared as males. All of them were assigned the male sex with removal of the female adnexa. Six were treated with male genitoplasty. Appropriate hormonal supplementation was offered after puberty. RESULTS: The mean age at presentation was 14.2 years (7 - 21). Six patients had presented after puberty, only one at seven years of age. Staged male genitoplasty comprising of chordee correction, male urethroplasty, and bilateral testicular prosthesis was performed. The female adnexa (uterus, ovaries, most of the upper vagina, and the fallopian tubes) were removed. The mental makeup was masculine in six and bigender in one. Bilateral mastectomy was performed at puberty in all. Hormonal treatment comprised of glucocorticoids and testosterone. Six patients were comfortable with the outcome of the masculinizing genitoplasty. One had a short-sized phallus. One had repeated attacks of urinary tract infection arising from the retained lower vaginal pouch. Social adjustments were good in all, except in one who had a bigender mental makeup. CONCLUSION: CAH patients with severe virilization presenting late and reared as males are extremely rare. However, the assigned gender can be retained adequately as males, meeting the socioeconomic compulsions of the society. The results are satisfactory following appropriate surgical procedures and hormonal supplementation.

A Case of a 46,XX Male with SRY Gene

46,XX male is a rare sex constitution characterized by the development of bilateral testis in persons who lack a Y chromosome. Manifestations of 46,XX males are usually hypogonadism, gynecomastia, azoospermia, and hyalinations of seminiferous tubules. The incidence of XX male reversal is approximately 1 in 20,000 male neonates. The SRYgene is located at the short arm of the Y chromosome(Yp11.31) and codes for testis determining factor in humans. Here, the patient, who presented with a normal male phenotype, was referred for azoospermia. Conventional cytogenetic analysis showed a 46,XX karyotype. Quantitative fluorescent polymerase chain reaction(QF-PCR) and Multiplex PCR studies identified SRY gene. And, Fluorescence In Situ Hybridization(FISH) confirmed the SRY gene on the distal short arm of chromosome X. We identified the SRY gene on the distal short arm of chromosome X by molecular cytogenetic and molecular analyses. Therefore, molecular-cytogenetics and molecular studies were proved to be clinically useful adjunctive tool to conventional prenatal cytogenetic analysis.

A Case of 46 XX Male Syndrome / 대한내분비학회지

The 46, XX male syndrome is rare disease that is characterized by a phenotypic male who has a 46, XX female karyotype. Since the first report by de la Chapelle and associates in 1964, several cases have been reported, but it is still a rare entity. Recently we examined a 20-year-old XX male who had the symptoms of gynecomastia, an infantile appearance of the external genitalia, scanty pubic hair, no Adams apple, and no axillary hair. We presently describe a patient with the 46, XX male syndrome who showed a 46, XX karyotype on chromosomal study and review the literatures.