The XX-male or sex reversal syndrome is a rare entity, which a is phenotypic man with a 46, XX female karyotype. Since it was first reported by la Chapelle and associates in 1964, more than 150 XX males have been reported. Recently we experienced a 18-year-old XX-male with gynecomastia and hypospadias. Clinical, endocrinological and genetically studies were presented and theories regarding the etiology of the XX-male syndrome were discussed with review of literatures.
46, XX Testicular Disorders of Sex Development ; Adolescent ; Female ; Gynecomastia ; Humans ; Hypospadias ; Karyotype ; Male

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.
46, XX Testicular Disorders of Sex Development* ; Female ; Genitalia ; Gynecomastia ; Hair ; Humans ; Karyotype ; Male ; Rare Diseases ; Young Adult

46,XX male sex reversal syndrome is, also called the de la Chapelle syndrome, a rare cause of abnormal sex determination with an incidence of 1 in 20,000~25,000 male neonates. The condition of 46,XX is characterized by testicular development in subject who have two X chromosomes but who lack a normal Y chromosome. All patients have small and azospermic testes and no evidence of ovarian tissue or Mullerian duct derivatives. XX males can be classified as Y positive or Y negative, depending on the presence or absence of Y specific sequences. SRY positive XX male have normal genitalia with a small penis, however, 10~15% of patients are SRY negative XX male, exhibit various degrees of genital ambiguity and can be diagnosed at birth or during early childhood. We experienced a case of sex determining region on the Y chromosome (SRY) negative 46,XX male syndrome neonate, with deletion on the long arm of X chromosome.
46, XX Testicular Disorders of Sex Development* ; Arm* ; Disorders of Sex Development ; Genitalia ; Humans ; Incidence ; Infant, Newborn ; Male ; Parturition ; Penis ; Testis ; X Chromosome* ; Y Chromosome

ObjectiveTo identify the etiology of chromosome abnormality in an infertile man and analyze the correlation between the genotype and phenotype.

METHODSWe 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.

RESULTSNegative 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.

CONCLUSIONSThe 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.

46, XX Testicular Disorders of Sex Development ; diagnosis ; genetics ; Chromosome Aberrations ; Chromosome Banding ; Genetic Testing ; Humans ; Infertility, Male ; genetics ; Karyotype ; Karyotyping ; Male ; Phenotype ; Sex-Determining Region Y Protein ; genetics

XX male has a male phenotype with testes or gonads of testicular type and a female chromosomal constitution of 46, XX with no evidence of either ovarian tissue or female genital organs. Generally, they have normal male genitalia and all are infertile. We experienced a neonate with anophthalmia, hypospadia, small penis, and normal testes, whose chromosomal analysis demonstrated 46, XX. Polymerase chain reaction revealed the existence of a sex-determining region of Y (SRY). These findings suggest that the translation of an SRY on the X chromosome led to the development of a male phenotype. We report the case with a review of the related literature.
46, XX Testicular Disorders of Sex Development* ; Anophthalmos ; Constitution and Bylaws ; Female ; Genitalia, Female ; Genitalia, Male ; Gonads ; Humans ; Hypospadias ; Infant, Newborn ; Male ; Penis ; Phenotype ; Polymerase Chain Reaction ; Testis ; X Chromosome

The 46, XX male or sex-reversal syndrome is a rare entity, which may be reported first by de la Chapelle and associates in 1964, an additional 135 cases have been recognized, yet only 20 percent of these patients have been diagnosed during childhood. The 46, XX male may be associated with hypogonadism and infertility in adult, and occasionally, sexual ambiguity in the neonate. At least 10% of patients have had hypospadia or ambiguous external genitalia. The 46, XX male was diagnosed with cytogenic study, H-Y antigen, hormonal study testicular biopsy, radiologic study. Here, we report a case of 19 month-old child XX-male with hypospadia and chordee.
46, XX Testicular Disorders of Sex Development* ; Adult ; Biopsy ; Child ; Female ; Genitalia ; H-Y Antigen ; Humans ; Hypogonadism ; Hypospadias ; Infant ; Infant, Newborn ; Infertility ; Male

The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.
46, XX Testicular Disorders of Sex Development ; Diagnosis ; Disorders of Sex Development ; Female ; Fluorescence ; Genes, sry ; Genetic Counseling ; Genitalia, Male ; Gonads ; Humans ; In Situ Hybridization ; Korea ; Male ; Phenotype ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Sexual Development* ; Testis

During the last 6.5 years 49 patients with inter sex were managed at the Department of Urology, Seoul National University Hospital. The median age was 8.8 years (from 2 months to 37 years). The patients consist of 15 female pseudohermaphroditism (adrenogenital syndrome), 4 true hermaphroditism, 21 male pseudohermaphroditism, 3 mixed gonadal dysgenesis, 3 Turner`s syndrome and 3 miscellaneous inter sex including Smith-Lemli-Opitz syndrome and Prader-Willi syndrome. Though early diagnosis and treatment are most important, only 10 patients (20%) were diagnosed before 2.5 years of age.
46, XX Disorders of Sex Development ; 46, XY Disorders of Sex Development ; Disorders of Sex Development* ; Early Diagnosis ; Gonadal Dysgenesis, Mixed ; Humans ; Ovotesticular Disorders of Sex Development ; Prader-Willi Syndrome ; Seoul ; Smith-Lemli-Opitz Syndrome ; Urology

PURPOSE: A change in gender assignment after 2 years of age is associated with severe psychological problems for the child and family. It is important that a definitive diagnosis be determined as quickly as possible. The treatment of ambiguous genitalia will be different by individual difference. We reviewed 16 cases of ambiguous genitalia patients with the object of encouraging early diagnosis and proper treatment individually. MATERIALS AND METHODS: We reviewed retrospectively 16 patients with ambiguous genitalia who were surgically managed at our department. Diagnostic workup included chromosomal analysis, blood and urine steroid measurement, hormonal study and radiologic study. The patients consisted of female pseudohermaphroditism in five cases, male pseudohermaphroditism in nine cases, true hermaphroditism and mixed gonadal dysgenesis in one case in each. The groups were analyzed according to karyotype, sex of rearing, age at diagnosis, age at operation, op procedure, post op complication and follow up. RESULTS: Five cases of female pseudohermaphroditism were raised as female in three cases and male in two cases, re-assigned and surgically corrected as four females and one male. Nine cases of male pseudohermaphroditism were raised as female in six cases and male in three cases, re-assigned and surgically corrected as three females and six males. One case of true hermaphroditism was surgically corrected as male. One case of mixed gonadal dysgenesis was surgically corrected as female and then given hormonal therapy. Four patients had sex conversion after 2 years of age. CONCLUSIONS: Though early diagnosis and treatment are most important, most patients were diagnosed and treated after 2 years of age. A continuous effort should be made to educate parents and alert attending physicians so that early diagnosis and treatment of these patients could be made as soon as possible.
46, XX Disorders of Sex Development ; 46, XY Disorders of Sex Development ; Child ; Diagnosis ; Disorders of Sex Development* ; Early Diagnosis ; Female ; Follow-Up Studies ; Gonadal Dysgenesis, Mixed ; Humans ; Individuality ; Karyotype ; Male ; Ovotesticular Disorders of Sex Development ; Parents ; Retrospective Studies

It is well known that proper gender assignment and treatment to a neonate born with ambiguous genitalia are extremely important. We reviewed seven patients with ambiguous genitalia who were surgically managed at our department during recent 5 years. The median age was 12.1 years (from 3 to 24 years) and patients consist of three female pseudohermaphroditism (adrenogenital syndrome), one true hermaphroditism, one male pseudohermaphroditism and two mixed gonadal dysgenesis. Three patients were managed with clitoral recession and vaginoplasty, each of them with clitoral recession vaginoplasty and gonadectomy, with clitoral recession and gonadectomy, with clitoral recession, with gonadectomy and bilateral mastectomy. One patient with adrenogenital syndrome was raised as male, but re-assigned and surgically corrected as female at her age of 16 years. Another one patient with true hermaphroditism was raised as male who underwent excision of female internal genitalia, gonadectomy and bilateral mastectomy in considering of patient's gender identity, appearance of external genitalia and parent's proposal although the karyotype was 46 XX. We suggest that gender assignment and surgical correction must be done as early as possible after full evaluation of fertility feasibility, karyotype, sex ability and patient and parent's proposal.
46, XX Disorders of Sex Development ; 46, XY Disorders of Sex Development ; Adrenogenital Syndrome ; Disorders of Sex Development* ; Female ; Fertility ; Gender Identity ; Genitalia ; Gonadal Dysgenesis, Mixed ; Humans ; Infant, Newborn ; Karyotype ; Male ; Mastectomy ; Ovotesticular Disorders of Sex Development