XX Ovotesticular Disorder Of Sex Development Research Articles

Genetic evaluation of disorders of sex development: current practice and novel gene discovery.

As the pace of genetic discovery accelerates, genetic sequencing is increasingly applied to rare disease such as DSD (differences or disorders of sex development,) which has led to an increase in the number of novel variant-containing candidate genes identified. In this review, we will discuss several candidate genes which have recently been proposed as causative of DSD, as well as novel work in understanding gene regulation in the mouse gonad that may have implications for the DSD phenotype in humans. We performed a comprehensive search of PubMed through August 2018 to identify relevant peer-reviewed publications from 2017 to 2018 on DSD genetics. Seminal work has identified a critical gonadal enhancer of Sox9 in a mouse model. This enhancer is located in a region which had previously been implicated in both XX and XY DSD, though the specific enhancer and its role in Sox9 gene expression had not been defined. Novel candidate genes in XY gonadal dysgenesis (SOX8, ESR2) and XX ovotesticular DSD (NR2F2) have been described.

46, XXovotesticular disorder of sex development with serous cystadenomas of the ovary

Ovotesticular disorder of sex development (DSD) is an extremely rare condition and is defined as presence of both ovarian and testicular tissue in the same individual, regardless of the karyotype and the status of the external or internal genitalia. This disorder was formerly called True hermaphroditism and 400-500 cases have been reported in literature till date. Various chromosomal abnormalities have been described but 46XX is the commonest. Both Mullerian and Wolffian duct derivatives are present in the same individual and the external as well as internal genitalia display a spectrum of phenotypes. The external genitalia are ambiguous and a uterus and a phallus areoften present. The gonads may be ovotestis or a combination of ovary on one side and testes or ovotestis on the other side. These gonads are prone to develop both benign and malignant neoplasms. Tumors like dysgerminoms, seminomas, gonadoblastoma, and mucinous cystadenomas have been described. Serous cystadenomas however, have not been described.

Coexistence of Trisomy 13 and SRY (−) XX Ovotesticular Disorder of Sex Development

ABSTRACTIntroduction: Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation characterized by the presence of both testicular and ovarian tissue in an individual and the majority of cases have been reported with 46,XX karyotype. In 46,XX cases, testicular differentiation may occur due to the translocation of SRY to the X chromosome or to an autosome. Case report: Herein, we present a female newborn with a combination of trisomy 13 and SRY (-) XX OT-DSD. Conclusion: Trisomy 13 is a relatively common and well-known chromosomal disorder in which disorders of sexual differentiation are not frequent. In the absence of SRY, overexpression of pro-testis genes, or decreased expression of pro-ovarian/anti-testis genes have been suggested as underlying mechanisms of testicular formation. The findings in this patient were suggestive of an underlying genomic disorder associated with FGF9 and/or SPRY2.

Management of children with disorders of sex development: 20-year experience in southern Thailand

Disorders of sex development (DSD) is a group of sexual differentiation disorders resulting in genital anomalies with defects in gonadal hormone synthesis and/or incomplete genital development. These conditions result in problems concerning the sex assignment of the child. This study aims to describe the clinical features, diagnosis and management of children with DSD in southern Thailand. The medical records of 117 pediatric patients diagnosed with DSD during the period of 1991-2011 were retrospectively reviewed. Disorders of sex development were categorized into 3 groups: sex chromosome abnormalities (53.0%), 46,XX DSD (29.9%) and 46,XY DSD (17.1%). The two most common etiologies of DSD were Turner syndrome (36.8%) and congenital adrenal hyperplasia (29.9%). Ambiguous genitalia/intersex was the main problem in 46,XX DSD (94%) and 46,XY DSD (100%). Sex reassignment was done in 5 children (4.3%) at age of 3-5 years: from male to female in 4 children (1 patient with congenital adrenal hyperplasia, 1 patient with 45,X/46,XY DSD, and 2 patients with 46,XX ovotesticular DSD) and from female to male in 1 patient with 46,XX ovotesticular DSD. Of the total 20 children with 46,XY DSD, 16 (80%) were raised as females. Management of DSD children has many aspects of concern. Sex assignment/reassignment depends on the phenotype (phallus size) of the external genitalia rather than the sex chromosome.

XX Maleness and XX True Hermaphroditism inSRY-Negative Monozygotic Twins: Additional Evidence for a Common Origin

Differentiation of testicular tissue in 46,XX individuals is seen either in XX males, the majority of them with SRY gene, or in individuals, usually SRY(-), with ovotesticular disorder of sex development (OT-DSD). Although they are sporadic cases, there are some reports on familial recurrence, including coexistence of XX maleness and OT-DSD in the same family. We report on a case of SRY(-) 46,XX monozygotic twins with genital ambiguity. Hormonal evaluation included testosterone, FSH, and LH measurements. SRY gene was investigated by PCR and two-step PCR in peripheral leukocytes and gonadal tissues, respectively. Direct DNA sequencing of the DAX-1 coding sequence was performed. Real-time PCR for SOX9 region on chromosome 17 was obtained. Both twins had a 46,XX karyotype. Twin A had a 1-cm phallus with chordee, penoscrotal hypospadias, and palpable gonads. Serum levels of FSH (2.34 mIU/ml), LH (8.8 mIU/ml), and testosterone (1.6 ng/ml) were normal, and biopsies revealed bilateral testes. Twin B had a 0.5-cm phallus, perineal hypospadias, no palpable gonad on the right, and a left inguinal hernia. Hormonal evaluation revealed high FSH (8.2 mIU/ml) and LH (15 mIU/ml) and low testosterone (0.12 ng/ml). Upon herniotomy, a right testis (crossed ectopia) and a small left ovotestis were found. SRY gene was absent in both peripheral leukocytes and gonadal tissue samples. Neither DAX-1 mutations nor SOX9 duplication was identified. This case provides evidence that both XX maleness and XX OT-DSD are different manifestations of the same disorder of gonadal development.