Testicular Disorder Of Sex Development Research Articles

P-40 A rare cause of male infertility: 46, XX testicular disorder of sex development

Abstract Introduction 46, XX testicular disorder of sex development (DSD) is a rare condition with an estimated incidence of 1 per 20,000 individuals. The clinical spectrum ranges from ambiguous genitalia that is usually diagnosed at birth, to male infertility that is diagnosed in the adult years. However, the diagnosis of 46, XX DSD in an individual presenting with infertility may be challenging due to occult clinical findings. A thorough physical examination as well as clinical suspicion is required for diagnosis. Clinical Case A 22-year-old male presented to the urology clinic for infertility despite at least 3 years of regular unprotected intercourse. On physical examination, his testicles were palpable bilaterally in the scrotum with small volumes. Laboratory results revealed hypergonadotropic hypogonadism and his spermiogram revealed azoospermia. Abdominopelvic ultrosonagraphy (US) was reported normal except abdominal situs inversus. Tumor markers for a probable testicular tumor were negative. He was referred to medical genetic department. His family history was unremarkable except for parental consanguineouty. The chromosomal analyze revealed a 46, XX karyotype, and fluorescence in situ hybridization (FISH) disclosed that the SRY gene locus was translocated to the X chromosome: 46,x,der(x) t(x;Y) (sry+); SRY + AZF a,b,c microdeletion. The patient was consulted to the endocrinology department for further evaluation of hypogonadism. On physical exam, he had eunuchoid habitus with incomplete virilization, bilateral and symmetric gynecomastia. The height, and body mass index of the patient was 165 cm, and 29.2 kg/m2, respectively. The testicles were bilaterally palpable in the scrotum, with a volume of 4 mL each. His luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone levels were 14 mUI/mL (laboratory reference: 1.5–9 mUI/mL), 42 mUI/mL (1.4–18 mUI/mL), and 140 ng/dl (197-700 ng/dL), respectively. The bone age matched his chronological age. Bone densitometry revealed osteopenia. A direct X-ray of the thorax showed thoracic situs inversus, he diagnosed with situs inversus totalis. Detailed genetic analyses could not be done concerning this diagnosis due to financial constraints. He had no history of lung infections that ruled out Kartagener's syndrome. Treatment was started with monthly intramuscular testosterone injections of 250 mg/ml. The patient and his family received genetic counseling, including advice that assisted reproduction will not work owing to AZFabc deletion. Conclusion 46, XX DSD is an uncommon genetic disorder that is rarely identified during the evaluation of male infertility. Clinical suspicion and a comprehensive physical exam are keys for diagnosis. Genetic analysis is essential for definitive diagnosis. A multidisciplinary is required for treatment and follow-up. Psychological support and genetic counseling are also critical for the management of these patients.

Unbalanced X;Y translocations carrying SRY in prenatal settings: Clinical, molecular, and cytogenetic analysis of three cases.

Generally, the translocation of SRY onto one of the X chromosomes leads to 46, XX testicular disorders of sex development, a relatively rare condition characterized by the presence of testicular tissue with a 46, XX karyotype. Three prenatal cases of unbalanced X; Y translocation carrying SRY were identified in this study. Structural variants were confirmed using single nucleotide polymorphism array and chromosomal karyotyping. X chromosome inactivation (XCI) was also analyzed. Detailed clinical features of the three cases were collected. We identified two fetuses with maternal inherited unbalanced X; Y translocations carrying SRY and skewed XCI presenting with normal female external genitalia, and one fetus with de novo 46, XX (SRY+) and random XCI manifested male phenotypic external genitalia. This study reports that cases with unbalanced X; Y translocations carrying SRY manifested a normal female external genitalia in a prenatal setting. We speculate that the skewed XCI mediates the silence of SRY. In addition, our study emphasizes that combining clinical findings with pedigree analysis is critical for estimating the prognosis of fetuses with sex chromosome abnormalities.

FRI446 A Case Of 46 XX Testicular Disorder Of Sex Development Presenting As Hypogonadism And Infertility

Abstract Disclosure: N. Balachandar: None. S. Agarwal: None. K.K. Soe: None. Introduction: Hypergonadotropic hypogonadism in males can be due to genetic, acquired or developmental causes. Common etiologies of testicular failure include trauma, systemic illnesses, radiotherapy, gonadotoxic drugs, and viral orchitis; in addition, genetic causes should be considered. Here, we present a case of primary hypogonadism and infertility due to 46 XX testicular disorder of sex development (DSD). Case Report: A male in his early fifties with history of obesity presented with fatigue to his PCP. A total testosterone level was 1.8 ng/mL (normal: 1.7 - 7.6 ng/mL) with a repeat value confirming the finding. Bioavailable testosterone was low at 85.1 ng/dL (normal: 110-575 ng/dL). FSH was elevated at 39.9 mIU/mL (normal: 1.3 - 19.3 mIU/mL), and LH was elevated at 16.6 mIU/mL (normal: 1.2 - 8.6 mIU/mL). In endocrinology clinic, he reported a year of fatigue, erectile dysfunction despite normal libido, and an inability to conceive despite three years of regular unprotected intercourse. He noted loss of muscle mass, bilateral breast tissue development, and reduction in testicular size. Physical exam revealed normal phallus, diffusely sparse body hair with atypical male distribution, bilateral gynecomastia, and bilateral reduction in testicular volume (right: 5 mL; left: 8 mL). Chromosomal analysis showed a mosaic pattern of 45 XO in 6% of cells and 46 XX in 94% of cells. Fluorescence in situ hybridization (FISH) analysis confirmed the presence of the sex-determining region (SRY) gene in 96% of cells. Metaphase FISH showed cryptic insertion of the SRY gene into the p arm of the X chromosome. Semen analysis showed azoospermia. He was diagnosed with 46 XX testicular DSD with abnormal mosaicism. He was prescribed testosterone gel and counseled on fertility options resulting in improvement of testosterone levels, sexual function, and subjective well-being. Discussion: The SRY gene, normally located on the p arm of the Y Chromosome, is responsible for development of primitive gonads into testicles during embryogenesis. Homologous recombination occurs between chromosomes during gametogenesis. It is hypothesized that in patients with 46 XX DSD, the SRY gene is translocated to the X chromosome, as demonstrated in this case. Its expression helps with selection of male sex in a growing fetus. Thus, in a 46 XX SRY positive male, the phenotypic presentation is male. Since the AZF gene on the q arm of the Y chromosome which is essential for spermatogenesis is not translocated, 46 XX males are infertile and undiagnosed until adulthood when azoospermia is noted during infertility workup. 46 XX SRY negative males develop ambiguous genitalia leading to earlier diagnosis. Eighty-percent of 46 XX males are SRY positive and twenty-percent are SRY negative. Thus, in adult males presenting with infertility and hypogonadism, genetic causes such as 46 XX DSD with SRY translocation should be considered. Presentation: Friday, June 16, 2023

Prenatal diagnosis of 46,XX testicular disorder of sex development with SRY-positive: A case report and review of the literature

We report a case of a fetus with 46,XX testicular disorder of sex development detected prenatally. This fetus was found abnormally due to non‐invasive prenatal testing. Amniocentesis revealed SRY gene on the X chromosome of the fetus. The related literature was reviewed, and the advantages and limitations of various prenatal diagnostic techniques were discussed. The combination of non‐invasive prenatal testing and various prenatal diagnostic techniques has enabled more fetuses with sex reversal to be detected.

Genetic and semen examination of patients with 46,XX testicular disorder of sex development

Background. 46,XX male syndrome (XX sex reversal) or 46,ХХ testicular disorder of sex development (DSD) – a genetic disorder that characterized by primary hypogonadism and male infertility because of severe spermatogenesis defects. 46,XX testicular DSD is resulted from unbalanced microstructural sex chromosome abnormalities, mostly X-Y translocations involving SRY gene. Genetic heterogeneity and phenotypic variability, particularly the effect of the genotype on semen parameters in XX sex reversed patients are not sufficiently studied.Aim. Genetic and semen examination in patients with 46,ХХ testicular DSD.Materials and methods. 32 patients with 46,XX testicular DSD and 2 men with mosaicism 46,XX/46,XY were examined. Cytogenetics, molecular genetics and spermatology examination (standard semen analysis and quantitative karyological analysis of immature germ cells) were performed.Results. The presence of the SRY gene was detected in 23 (82.1 %) of 28 patients who underwent a molecular genetic study, and 5 patientswere SRY-negative. Azoospermia and severe oligozoospermiawere diagnosed in 24 (75 %) and 8 (25 %) patients, respectively. Quantitative karyological analysis of immature germ cells allowed to reveal cryptozoospermia in 3 patients with initially diagnosed azoospermia (according to a standard semen analysis). Severe oligozoospermia and cryptozoospermia were mentioned both in some of SRY-positive and SRY-negative patients.Conclusion. 46,XX testicular DSD is characterized by severe degree of spermatogenesis defects (azoospermia and extremely severe oligozoospermia). Small number of germ cells detected in ejaculate in some patients with 46,XX testicular DSD, including SRY-negative individuals, indicates partial preservation ofspermatogenesisin the absence of Y chromosome genes.

Testicular Architecture of Men with 46,XX Testicular Disorders of Sex Development

Background: A subtype of disorders of sex development (DSD) in individuals with a 46,XX karyotype who are phenotypically male is classified as testicular DSD (46,XX TDSD). These individuals develop testes but are infertile due to germ cell loss. However, little is known about their testicular architecture. Methods: We analyzed biopsies of four SRY positive 46,XX TDSD men for testicular architecture, Sertoli (SCs) and Leydig cells (LCs). These were compared with biopsies of men with normal spermatogenesis (NS, n = 4), men with Klinefelter syndrome, 47 XXY (KS, n = 4), and men with AZF deletions (AZF, n = 5). Testicular architecture was evaluated and SCs and LCs were analyzed for specific markers (SC: SOX9, DMRT1; LC: INSL3). Results: A smaller number of tubules, more SOX9-negative but similar proportions of DMRT1-negative SCs were found in 46,XX TDSD compared to NS. The lower number of tubules and severe LC hyperplasia observed in 46,XX TDSD were similar to KS. Conclusion: Testicular architecture and marker expression of SCs and LCs in 46,XX TDSD men display unique patterns, which are discernable from chromosomal aneuploidies. Given the reduced Y-chromosomal gene content in 46,XX TDSD, the supernumerary X chromosome effects may be decisive regarding the damage on testicular composition and endocrine function.

A clue to the etiology of disorders of sex development from identity-by-descent analysis in dogs with cryptic relatedness.

Disorders of sex development (DSDs) are discrepancies between sex chromosomes and phenotypical sex. Quite common forms of DSD in canine populations include testicular and ovotesticular XX DSDs with a normal set of sex chromosomes. The objective of this study was to identify genes and putative harmful variants for canine XX DSDs. I have reanalyzed data from the whole-genome sequencing of 11 XX DSD French Bulldogs and six XX DSD American Staffordshire Terriers. Identity-by-descent analysis revealed cryptic relatedness in affected French Bulldogs. Causative genes were sought in chromosomal segments shared identical-by-descent by close relatives. In French Bulldogs, the reanalysis identified 19 regions of importance with a total length of just 65.9Mb. Variant filtering within the regions implicated AKAP2, PIWIL1, POLR3A and SH2D4B as genes that may be involved in individual cases of testicular and ovotesticular XX DSD in French Bulldogs and American Staffordshire Terriers.

PMON270 Coexistence of 46, XX Testicular Disorder of Sex Development and 11β-Hydroxylase Deficiency: In Vivo and In Vitro Studies

Abstract Background 46, XX testicular disorder of sex development and 11β-hydroxylase deficiency (11β-OHD) are two extremely rare types of disorder of sex development (DSD). No coexistence has been reported yet. Clinical Case A 22-year-old male showed small testes (volume=4ml) and gynecomastia for 2 years. At the age of 3.5, he was diagnosed as simple virilizing type of 21-hydroxylase deficiency (21-OHD) for the manifestations of the enlarged penis (length=7.5cm), hyperpigmentation, and normal blood pressure. Adrenal ultrasound suggested bilateral adrenal hyperplasia (both length * width = 2.4*0.9cm) and X-ray showed accelerated bone age (12.5 years old). Irregular cortisone acetate 6.25mg per day was administrated since then. At the age of 18, he was sent to emergency for aortic aneurysm rupture and heart failure, and hypertension urgency was diagnosed. Sanger sequencing revealed that he carried compound heterozygous variants in CYP11B1 gene: NM_000497.3: c.905_907delinsTT and NM_000497.3: c.954+7C>T, which were respectively inherited from his father and mother. Pathogenesis of the novel intron variant (c.954+7C>T) was further verified in COS7, CHO, and 273T cell lines by transfecting wild-type and mutant-type minigene, extracting RNA of cells, reversing RNA into cDNA, PCR, and Sanger sequencing. The result showed that the c.954+7C>T variant introduced a cryptic donor splice site at a site 5 bp downstream of the 3' natural splice donor site of exon 5. The level of adrenal steroids detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was consistent with the characteristics of 11β-OHD. The patient was treated by neoplasty of thoracic aortic aneurysm and added anti-hypertension drugs in addition to glucocorticoid after surgery. Unexpectedly, the abnormalities of male characteristics including small testes and gynecomastia appeared since adolescence. Laboratory tests showed an elevated level of FSH and LH and azoospermia. Scrotum Ultrasound showed bilateral testicular dysplasia (right: 1.9*1.4*0.8cm, left: 1.9*1.3*0.8cm). To figure out the unexplainable results, whole-exome sequencing was performed and revealed two copy number variants: the duplication of Xp22.33-q28 which spans 151.32Mb, and the deletion of Yp11.2-q11.23 which spans 23.34Mb. Meanwhile, the karyotype test by culturing blood lymphocytes showed 46, XX (100/100), which confirmed the diagnosis of 46, XX testicular DSD. Fluorescence in situ hybridization (FISH) revealed the presence of the SRY gene, which is translocated into the short arm of the X chromosome. Testosterone replacement is unnecessary for the normal level of testosterone (T) (4.44ng/ml, N: 1.75-7.81ng/ml), which is the result of the combined action of 11β-OHD with adrenal T accumulation and 46, XX testicular DSD with testicular T deficiency. Assisted reproduction consulting should start early. Conclusion This is the first case demonstrating the possibility of coexistence of 46, XX testicular DSD and 11β-OHD and hinting at the significance of a combination of clinical and molecular diagnostic methods. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Evidence for high breakpoint variability in 46, XX, SRY-positive testicular disorder and frequent ARSE deletion that may be associated with short stature.

The translocation of SRY onto one of the two X chromosomes results in a 46,XX testicular disorder of sex development; this is supposedly because of non-allelic homologous recombination between the protein kinase X gene (PRKX) and the inverted protein kinase Y pseudogene (PRKY). Although 46,XX SRY-positive men are infertile, the literature data indicate that some of these individuals are of short stature (relative to the general population). We sought to determine whether short stature was linked to additional, more complex chromosomal rearrangements. Twelve laboratories gathered detailed clinical, anthropomorphic, cytogenetic and genetic data (including chromosome microarray data) on patients with 46,XX SRY-positive male syndrome. SRY was present (suggesting a der(X)t(X;Y)) in 34 of the 38 cases (89.5%). When considering only the 20 patients with chromosome microarray data, we identified several chromosomal rearrangements and breakpoints, especially on the X chromosome. In the five cases for whom the X chromosome breakpoint was located in the pseudoautosomal region, there was partial duplication of the derivate X chromosome. In contrast, in the 15 cases for whom the breakpoint was located downstream of the pseudoautosomal region, part of the derivate X chromosome had been deleted (included the arylsulfatase E [ARSE] gene in 11 patients). For patients with versus without ARSE deletion, the mean height was, respectively, 167.7±4.5 and 173.1±4.0cm; this difference was not statistically significant (p =0.1005). Although 46,XX SRY-positive male syndromes were mainly because of imbalanced crossover between the X and Y chromosome during meiosis, the breakpoints differed markedly from one patient to another (especially on the X chromosome); this suggests the presence of a replication-based mechanism for recombination between non-homologous sequences. In some patients, the translocation of SRY to the X chromosome was associated with ARSE gene deletion, which might have led to short stature. With a view to explaining this disorder of sex development, whole exome sequencing could be suggested for SRY-negative patients.

Whole genome sequencing identifies a missense polymorphism in PADI6 associated with testicular/ovotesticular XX disorder of sex development in dogs

Disorders of sex development (DSDs) are congenital malformations defined as discrepancies between sex chromosomes and phenotypical sex. Testicular or ovotesticular XX DSDs are frequently observed in female dogs, while monogenic XY DSDs are less frequent. Here, we applied whole genome sequencing (WGS) to search for causative mutations in XX DSD females in French Bulldogs (FB) and American Staffordshire Terries (AST) and in XY DSD Yorkshire Terries (YT). The WGS results were validated by Sanger sequencing and ddPCR. It was shown that a missense SNP of the PADI6 gene, is significantly associated with the XX DSD (SRY-negative) phenotype in AST (P = 0.0051) and FB (P = 0.0306). On the contrary, we did not find any associated variant with XY DSD in YTs. Our study suggests that the genetic background of the XX DSD may be more complex and breed-specific.

46XX testicular DSD SRY-Negative in a child with hypoplastic left heart syndrome

Disorders of Sex Development (DSD) refers to biological differences between phenotypic sex, gonad morphology and chromosomal material. A full-term infant was born with Hypoplastic Left Heart Syndrome (HLHS) and ambiguous genitalia. Karyotype revealed 46XX with no evidence of Y chromosome or SRY. Biopsy of both gonads revealed testicular tissue. Parents decided to rear the child as male. The child underwent extensive cardiac repair and is currently awaiting decision regarding urological repair. This case emphasizes the need for multidisciplinary care in the management of children with DSD associated with other complex medical conditions to ensure a timely diagnosis and multi-system, patient-centered treatment approach.

46XX Testicular Disorder of Sex Development.

46XX Testicular Disorder of Sex Development.

46, XX Testicular Disorder of Sex Development: A Case Report.

46, XX Testicular Disorder of Sex Development: A Case Report.

Generation of an induced pluripotent stem cell line GZHMCi008-A derived from a patient with SRY-positive 46,XX testicular disorder of sex development

The testicular disorder of sex development (TDSD) is a rare condition characterized by a male appearance with a female karyotype. The most frequent cause of TDSD is misplacement of the sex determining region Y (SRY) gene on the X chromosome. Here, we report the generation of an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a patient with SRY-positive 46,XX TDSD. This cell line offers an unprecedented cellular model to investigate the profound manifestations like infertility of the male sex reversal patients, and serves as a useful tool to develop therapies for the disease.

WT1 Pathogenic Variants are Associated with a Broad Spectrum of Differences in Sex Development Phenotypes and Heterogeneous Progression of Renal Disease

Wilms’ tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of WT1 have been classically associated with Denys–Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between WT1 disorders has been frequently observed. New WT1 variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic WT1 variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of WT1 between exons 9 and 10. Two pathogenic missense WT1 variants were identified in two 46,XY individuals with Wilms’ tumors; both patients were <1 year of age at the time of diagnosis. A novel WT1 variant, c.1453_1456 (p.Arg485Glyfs*14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with WT1 variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.

22q13 Duplication in Newborn With Dysmorphic Features: The Role of SOX10 in Disorders of Sex Development

Background: The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male reversal, 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% are SRY-negative. Here we present a 2 week old with discrepant prenatal karyotype and infant phenotype. Case: This 2-week-old had dysmorphic features (bitemporal narrowing, broad and flat nasal bridge, bilateral epicanthal folds) and multiple congenital anomalies; IUGR, hypertelorism, cleft lip and palate, ASD, small kidneys, sacral dimple. Physical exam revealed palpable inguinal masses and microphallus without hypospadias. Postnatal karyotype showed a 46,XX chromosome complement with duplication of 22q13-qter. He was negative for SRY gene by FISH. Microarray analysis confirmed the duplication encompassing the SOX10 gene. Lab evaluation showed LH 10.81 mIU/ml, FSH 3.21 mIU/ml and total testosterone 241 ng/dl. These values are consistent with activation of the hypothalamic–pituitary–gonadal axis during the neonatal period in males. Conclusion: Our case along with previous cases supports the existence of a gene on chromosome 22q that can trigger testis determination in the absence of SRY. Potential mechanisms responsible for ovotesticular disorder in the XX (SRY−) individual could involve activation of testis specifying genes in the absence of SRY and/or inadequate expression of pro-ovary/anti-testis genes such as SOX 8 and SOX9. SOX10, a gene closely related to SOX9 and SOX8, and its overexpression has been suggested as a candidate for 46,XX DSD. Over-expression of SOX10 in mice resulted in the XX DSD. The spectrum of sex reversal phenotypes and gonadal asymmetryseen in the Sox10 transgenic mice closely mirrors the range of gonadal and reproductive tract anomalies seen in cases of partial duplication of human chromosome 22q13. 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.

SRY-Positive 46-XX Testicular Disorder of Sex Development as a Rare Cause of Male Hypergonadotropic Hypogonadism: A Case Report

SRY-Positive 46-XX Testicular Disorder of Sex Development as a Rare Cause of Male Hypergonadotropic Hypogonadism: A Case Report

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±8.0cm. 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.

A Rare Case of Sry-Negative 46,XX Testicular Disorder of Sex Development with Complete Masculinization: A Case Report and Literature Review

46,XX testicular disorder of sex development is a rare cause of male infertility. There is a disagreement between the manifested sexual phenotype (male) and the genotype (female). It occurs in males with 46,XX karyotype who may have normal or ambiguous male genitalia, testosterone deficiency and infertility. With adequate hormonal treatment, the chance of having a good quality of life is high. In the diagnosis, the genetic study is fundamental for the identification of the gene that causes the disorder. The role of SRY gene is important because it allows classifying these males into two groups: those with SRY gene, which activates male sexual differentiation, translocated from Y chromosome to X (SRY-positive), and those without this translocation (SRY-negative). 80-90% of cases are SRY-positive. In the 1020% SRY-negative it is difficult to identify the gene responsible for the alteration. This would indicate the involvement of other genes linked to the X chromosome. This is a review of the first case of SRY-negative 46,XX testicular disorder of sex development with complete masculinization reported in Basque Country in which the cause of the disorder is being investigated, even without specifying.

Testicular disorder of sexual development with cryptorchidism, penile hypoplasia and hypospadias in a giraffe (Giraffa camelopardalis giraffa).

Disorders of sexual development (DSD) in wild mammals are rarely described. A male South African giraffe (Giraffa camelopardalis giraffa) was identified with bilateral cryptorchidism. The testes were intra-abdominal, smaller and less ovoid than in normal male giraffes. The right testis was situated more cranially than the left and connected to a longer deferent duct with normal ampullae. One distended vesicular gland filled with mucoid material was identified. A short penis, situated in the perineal area, was directed caudally and presented hypospadias. Histologically, testicular hypoplasia was present; the epididymis tubules contained no spermatozoa and the deferent duct and vesicular gland were inflamed. The blood testosterone concentration was 16.27 nmol/L and oestrone sulphate concentration was 0.03 ng/mL. The aetiology of the abnormalities is unknown.