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

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

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 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

A 30-year-old man with male phenotype visited our Infertility Clinic because of infertile marital life for 5 years. On physical examination, height was 162cm and body weight 52kg. Size of testis was 5 ml and that of penis, 6cm in length and 6cm in circumference. Distribution of pubic hair was sporadic and inverted triangle shape. No gynecomastia was obsessed. urogenital sinus or Mullerian duct system was not found in retrograde cystourethrography. Hormonal assay revealed that plasma FSH (46.6 IU/L) and LH (48.4 IU/L) were found to be elevated but testosterone (5.35 ng/ml) was within normal range. Prolactin level (21.1 ng/ml) was also normal. Repeated semen analyses showed that no sperm in 1.5-2.0 ml of ejaculates. Histology of testis revealed that hyalinization of seminiferous tubules and Leydig cell hyperplasia. Chromosomal analysis with peripheral blood revealed that 46XX by repeated analyses. This is first case report of XX male syndrome or sex reversal syndrome from Korea.
46, XX Testicular Disorders of Sex Development* ; Adult ; Body Weight ; Gynecomastia ; Hair ; Humans ; Hyalin ; Hyperplasia ; Infertility ; Korea ; Male ; Penis ; Phenotype ; Physical Examination ; Plasma ; Prolactin ; Reference Values ; Semen Analysis ; Seminiferous Tubules ; Spermatozoa ; Testis ; Testosterone