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 / 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 Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication

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.

A Case of Molecular Analysis of XX Male Syndrome / 대한법의학회지

Sex typing may become the start point in investigations that are usually performed through amelogenin typing. In cases involving genotype-phenotype discrepancy, amelogenin typing could yield misleading results. The rare XX male syndrome is characterized by a phenotypic male with a 46, XX female karyotype. In this point, this case report would help understand the importance of genotype-phenotype discrepancy.

46,XX, der(15),t(Y;15)(q12;p11) karyotype in an azoospermic male.

We report on a Yq/15p translocation in a 23-year-old infertile male referred for Klinefelter Syndrome testing, who had azoospermia and bilateral small testes. Hormonal studies revealed hypergonadotropic hypogonadism. Conventional cytogenetic procedures giemsa trypsin giemsa (GTG) and high resolution banding (HRB) and molecular cytogenetic techniques Fluorescence In Situ Hybridization (FISH) performed on high-resolution lymphocyte chromosomes revealed the karyotype 46,XX, t(Y;15)(q12;p11). SRY-gene was confirmed to be present by classical Polymerase Chain Reaction (PCR) methods. His father carried de novo derivative chromosome 15 [45,X, t(Y;15)(q12;p11)] and was fertile; the karyotype of the father using G-band technique confirmed a reciprocal balanced translocation between chromosome Y and 15. In the proband, the der (15) has been inherited from the father because the mother had a normal karyotype (46,XX). In the proband, the der (15) could have produced genetic imbalance leading to unbalanced robertson translocation between chromosome Y and 15, which might have resulted in azoospermia and infertility in the proband. The paternal translocation might have lead to formation of imbalanced ova, which might be resulted infertility in the proband. Sister's karyotypes was normal (46,XX) while his brother was not analyzed.

Varón 46 XX, un desorden del desarrollo sexual testicular: a propósito de un caso clínico / 46 XX disturbance of testicular sexual development: report of one case

We report a previously healthy child that consulted for the first time at the age of 11 years for short stature. At that moment, his height was 138 cm, with a mid-parental target height of 175 cm. He was in an initial pubertal stage with a Tanner II pubic hair and a testicular volume of 4 ml. Initial laboratory examination was normal and the child had a concordant bone age. He consulted again at 16 years of age, with a height of 162.4 cm (percentile 5 for age), a bone age of 18 years and a Tanner IV pubic hair, but the testicular volume persisted at 4 ml. A genetic study disclosed a 46 XX karyogram and a fluorescence in situ hybridization (FISH) for chromosomes X and Y that showed a positive sex determining region Y (SRY) in X chromosome.

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 SRY Negative 46, XX Male Syndrome with Deletion on Long Arm of X Chromosome / 대한주산의학회잡지

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.

A Case of SRY Positive 46,XX Male / 대한소아내분비학회지

46,XX male is a rare abnormality of sex determination with an incidence of 1 in 20,000 male neonates. The clinical manifestations of 46,XX males are usually hypogonadism, gynecomastia, azoospermia, and hyalinations of seminiferous tubules, with altered hormonal levels at puberty. Less frequently, some sexual ambiguities are found, always with sterility owing to reduced testicular development. The origin of male phenotype in 46,XX male could be the results of at least three different mechanisms:translocations of Y sequence, including the SRY gene, to an X chromosome or to an autosome(about 90% of cases); a mutation in a yet unknown X-linked or autosomal gene in the testis-determinating pathway, and cryptic Y chromosome mosacism. We experienced a case of SRY-positive 46,XX male in a 21-year-old man with small testes. (J Korean Soc Pediatr Endocrinol 2003;8:184-188)

A Case of SRY Positive 46,XX Male / 대한소아내분비학회지

46,XX male is a rare abnormality of sex determination with an incidence of 1 in 20,000 male neonates. The clinical manifestations of 46,XX males are usually hypogonadism, gynecomastia, azoospermia, and hyalinations of seminiferous tubules, with altered hormonal levels at puberty. Less frequently, some sexual ambiguities are found, always with sterility owing to reduced testicular development. The origin of male phenotype in 46,XX male could be the results of at least three different mechanisms:translocations of Y sequence, including the SRY gene, to an X chromosome or to an autosome(about 90% of cases); a mutation in a yet unknown X-linked or autosomal gene in the testis-determinating pathway, and cryptic Y chromosome mosacism. We experienced a case of SRY-positive 46,XX male in a 21-year-old man with small testes. (J Korean Soc Pediatr Endocrinol 2003;8:184-188)

A Case of XX Male Syndrome with Anophthamia

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.

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.

A Case of 46 , XX Male / 대한산부인과학회잡지

46, XX male is a rare sex cluomasomal constitution characterized by the development of bilateral testis in persons who lack a Y chomosome. The majority of affected persons have normal external genitalia and usually seek medical advice due to infertility, hypogonadism and/or gynecomastia in adulthood. Although Y chromosomsl sequences can be detected in the majority of male subjects with 46, XX karyotype, several studies have shown thst approximately 10 % of patients lack Y chromosomal material including the SRY ( sex-determining region of Y-chromosome) gene. Several hypothesis have been proposed to explain the etiology of this constitution. 1. Translocation of the testis-determining factor (TDF) fiom the Y to the X chromosome or autosome. 2. Acquisition of Y chromosome function by a mutant autosomal or X-linked gene. 3. Undetected mosaicism with Y-bearing cell line 4. Loss of Y chmmosome hom the XXY Klinefelter zygote. We experienced a case of 46, XX male who was 30 years old. We report a case with review of the literature.

A case of XX male syndrome / 대한비뇨기과학회지

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.

XX-Male Syndrome: A Case Report / 대한비뇨기과학회지

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.

XX Male Syndrome / 대한비뇨기과학회지

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.