Search

Background: 46,XX complete gonadal dysgenesis (46,XX-CGD) is a rare disorder of sexual development (DSD) characterized by primary amenorrhea and a lack of spontaneous pubertal development in individuals with a 46,XX karyotype despite the presence of female internal and external genitalia due to failure of bilateral ovarian development. The condition is genetically heterogeneous, and in most cases, its etiology is unknown. Determining the genetic cause would provide insights into potential targets for genetic diagnosis and counseling. Methods: To clarify the molecular mechanisms of 46,XX complete gonadal dysgenesis in the population of China, whole-exome sequencing (WES) was performed on DNA samples from patients with 46,XX-CGD. In silico analysis was conducted to predict the pathogenicity of the variants. Results: We recruited 20 patients with 46,XX-CGD and identified 8 variants in 6 genes, including three homozygous variants in MCM9, POF1B, and PSMC3IP; compound heterozygous variants in TWNK; and three heterozygous variants in TP63 and INSRR, from 7 patients. These variants included 3 recurrent variants and 5 novel variants. Conclusions: This study identified several novel variants, broadening the variant spectrum of 46,XX-CGD. 46,XX-CGD is a genetically heterogeneous condition, and WES is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggest that WES is valuable for detecting 46,XX-CGD, which may lead to early interventions for patients. [ABSTRACT FROM AUTHOR]

Centrosomes have critical roles in microtubule organization, ciliogenesis, and cell signaling. 1,2,3,4,5,6,7,8 Centrosomal alterations also contribute to diseases, including microcephaly, cancer, and ciliopathies. 9,10,11,12,13 To date, over 150 centrosomal proteins have been identified, including several kinases and phosphatases that control centrosome biogenesis, function, and maintenance. 2,3,4,5,14,15,16,17,18,19,20,21 However, the regulatory mechanisms that govern centrosome function are not fully defined, and thus how defects in centrosomal regulation contribute to disease is incompletely understood. Using a systems genetics approach, we find here that PPP2R3C, a poorly characterized PP2A phosphatase subunit, is a distal centriole protein and functional partner of centriolar proteins CEP350 and FOP. We further show that a key function of PPP2R3C is to counteract the kinase activity of MAP3K1. In support of this model, MAP3K1 knockout suppresses growth defects caused by PPP2R3C inactivation, and MAP3K1 and PPP2R3C have opposing effects on basal and microtubule stress-induced JNK signaling. Illustrating the importance of balanced MAP3K1 and PPP2R3C activities, acute overexpression of MAP3K1 severely inhibits centrosome function and triggers rapid centriole disintegration. Additionally, inactivating PPP2R3C mutations and activating MAP3K1 mutations both cause congenital syndromes characterized by gonadal dysgenesis. 22,23,24,25,26,27,28 As a syndromic PPP2R3C variant is defective in centriolar localization and binding to centriolar protein FOP, we propose that imbalanced activity of this centrosomal kinase-phosphatase pair is the shared cause of these disorders. Thus, our findings reveal a new centrosomal phospho-regulatory module, shed light on disorders of gonadal development, and illustrate the power of systems genetics to identify previously unrecognized gene functions. • PP2A phosphatase subunit PPP2R3C localizes to the distal end of centrioles • PPP2R3C acts with FOP and CEP350 to oppose centrosomal kinase MAP3K1 • Imbalance of PPP2R3C/MAP3K1 activity impairs centrosome function and cell fitness • Impaired phospho-regulation at centrioles may underlie gonadal dysgenesis disorders Ganga et al. show that the PP2A phosphatase subunit PPP2R3C and the kinase MAP3K1 are centriolar proteins that functionally oppose each other. Imbalance of their activities impairs centrosome function and cell fitness and is further revealed as a shared basis of gonadal dysgenesis disorders caused by mutations in MAP3K1 and PPP2R3C. [ABSTRACT FROM AUTHOR]

Background: Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that lead to the dysfunction of the steroidogenesis pathway, resulting in steroid hormone deficiency of varied intensity. The cholesterol side-chain cleavage enzyme (P450scc), coded by the CYP11A1 gene, is vital to the first step in the biosynthesis of steroid hormones, which is the conversion of cholesterol to pregnenolone. Therefore, its deficiency causes a general steroid hormone shortage. Objective: We report a case of CAH caused by P450scc deficiency with complete 46, XY sex reversal, characteristic facial features (narrow middle section of the face, small ears with thick helix, fleshy upturned lobules), and dysmorphic macrocephaly along with shortened upper and lower extremities. Results: Our patient carries a compound heterozygotic pathogenic variant of the CYP11A1 gene, with two frameshift pathogenic variants NM_000781.3(CYP11A1):c.358del (p.Arg120Aspfs*18) in exon 2 and NM_000781.3(CYP11A1):c.835del (p.Ile279Tyrfs*10) in exon 5. To date, only around 50 cases with CYP11A1 pathogenic variants have been reported worldwide. We believe this is the first described case of a newborn with severe, classic P450scc deficiency in Poland. Conclusions: CYP11A1 (P450scc) deficiency is a rare and complex disorder that leads to primary adrenal insufficiency and may present with 46, XY disorders of sex development (DSD), phenotypic variations, and associated endocrinological abnormalities. This case, along with others cited, highlights the diverse presentations of DSD in individuals with pathogenic CYP11A1 variants. Optimal management necessitates a multidisciplinary approach by a specialized DSD team. Gonadectomy is a key consideration to decrease the teratogenic risk associated with intra-abdominal gonadal tissue. [ABSTRACT FROM AUTHOR]

Background:DHX37 is an autosomal gene responsible for encoding a helicase from the DExD/H-box family that plays an essential role in ribosome biogenesis. Variants in this gene were previously reported in two different phenotypes: neurodevelopmental disorders and disorders/differences of sex development (DSD). Particularly for the DSD group, variants were mainly reported associated with gonadal dysgenesis and testicular regression syndrome. Summary: Focusing specifically in the DSD group, we revised the 21 DHX37 variants described across a total of 55 cases published in the literature so far. We summarized the most important clinical and molecular features of all cases, trying to have a better comprehensiveness about this gene in the sexual development. Key Messages: The trick question regarding DHX37 is how a helicase involved in basic cell function could have a specific role in testis development. Little is known about the impact of DHX37 variants in DSD individuals. Nevertheless, current research strongly suggests that DHX37 is involved in the male sex development pathway, particularly in testis determination and maintenance. This is evidenced by the predominant assignment of affected individuals as males and the presence of Wolffian structures in most of the cases. Advancements in molecular techniques, such as the generation of induced pluripotent stem cells and the digenic inheritance for DHX37 cases, are also addressed in this paper. This represents the first comprehensive review of all DHX37 variants published in the literature to date. [ABSTRACT FROM AUTHOR]

Objective: Mixed gonadal dysgenesis (MGD) is an uncommon chromosomal Disorder of Sexual Development (DSD). There is insufficient information regarding clinical findings and growth patterns. This study aimed to provide more information about mixed gonadal dysgenesis, which has not yet been sufficiently defined. Materials and Methods: Data from 10 patients diagnosed with mixed gonadal dysgenesis were retrospectively reviewed. Clinical presentations, complaints at admission, imaging, genetic results, and treatments received by the patients were examined. Gonadal status and the gender of the patients were reared and evaluated by a multidisciplinary council decision. If received, growth hormone treatment doses and height gains were examined. Results: The patients’ ages at admission range from 6 months to 17.5 years. The median height SDS of the patients was −0.75 (2.73), the mean body weight SDS was −0.49 (±1.46), and the mean body mass index (BMI) SDS was 0.26 (±0.97). The complaints at admission varied, including ambiguous genitalia, short stature, and absence of menstruation. Some patients are completely in the female phenotype, while some are inadequately virilized male phenotype. External Masculinization Score (EMS) ranges from 1 to 6.5. The decision to raise 6 patients as female and 4 patients as male was made by a multidisciplinary council. Growth hormone treatment was administered to patients raised as female and diagnosed with short stature. The height SDS gain in treated patients was 0.42 (±0.49). Conclusion: Due to its rarity and varied clinical presentation, our knowledge about mixed gonadal dysgenesis is limited. Therefore, early diagnosis and individualized treatment plans are crucial for this patient group. [ABSTRACT FROM AUTHOR]

Mixed gonadal dysgenesis (MGD) is a disorder of sex development caused by mosaicism of the Y chromosome, represented by 45,X/46,XY. Prophylactic gonadectomy is recommended as soon as possible after its diagnosis, owing to a high risk of malignancy. In the present case, a 21-year-old woman presented with primary amenorrhea. Although the patient's external genitalia were female, the patient exhibited a hypoplastic uterus, wherein the ovaries were difficult to identify. The patient's height was 146 cm; they had cubitus valgus and webbing of the neck, leading to the consideration of a disorder of sex development. Chromosomal examination revealed 45,X/46,XY mosaicism. Thus, the patient was diagnosed with MGD. After thorough counseling, laparoscopic bilateral gonadectomy was performed. Pathological examination revealed a gonadoblastoma of the left gonad. Postoperatively, the patient had no recurrence and continued on Kaufmann therapy. In conclusion, prophylactic gonadectomy is recommended immediately following a diagnosis of MGD; however, the timing of the surgery should be carefully considered and adequate counseling should be conducted by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Disorders of sex development (DSD) result from intrauterine defects in sex discrimination. The clinical phenotype differs based on the disease type. Cases with ambiguous external genitalia are diagnosed at birth. However, diagnosis of cases with normal-appearing external genitalia may be delayed until puberty. Here, we report a patient with a pelvic mass and a small uterus that was diagnosed by abdominal ultrasound, in addition to the history of primary amenorrhea and physical examination suggested Swyer syndrome, confirmed by genetic karyotyping. Pathological examination of the surgically removed mass revealed dysgerminoma. Until the age of 19, the patient did not have any idea about 46, XY karyotype, and assumed to be a female. The development of dysgerminoma (as a result of the simultaneous presence of gonadal dysgenesis and Y-chromosome) was another challenge that the patient had to deal with. The diagnosis of this patient at an earlier age could have prevented the development of gonadoblastoma, by removal of the streak gonads. By the presentation of this case, we intend to increase the physician's awareness about DSDs; earlier diagnosis may help the patient deal with her disease better and reduce the risk of further complications. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a commonly used environmental toxicant, is easily exposed to the human body and causes testicular damage, sperm abnormalities, DNA damage and apoptosis, and interferes in the process spermatogenesis and steroidal hormone production along with obstruction in testes and epididymis development. Zinc (Zn), a potent regulator of antioxidant balance, is responsible for cellular homeostasis, enzymes and proteins activities during spermatogenesis for cell defence mechanisms in the testes. Selenium (Se) is required for spermatogenesis, antioxidant action and in the activities of different selenoproteins. Both Zn and Se are essential simultaneously for the proper regulation of spermatogenesis and sperm maturation as well as protection against chemical and disease-associated germ cell toxicity. Thus, the study aimed to understand the importance and beneficial effect of Zn and Se co-treatment against BPA-exposed testicular damage in rats. BPA 100 and 200 mg/kg/day was exposed through an oral gavage. Zn (3 mg/kg/day) i.p. and Se (0.5 mg/kg/day) i.p. were injected for 8 weeks. The testicular toxicity was evaluated by measuring body and organs weight, biochemical investigations, sperm parameters, testicular and epididymal histopathology, quantification DNA damage by halo assay, DNA breaks (TUNEL assay), immunohistochemistry and western blot. Results revealed that Zn and Se co-treatment ameliorated BPA-associated male gonadal toxicity in rat as revealed by decreased SGPT, SGOT and BUN levels in serum, reduced testes and epididymis tissue injury, DNA breaks, apoptosis, expressions of 8-OHdG, γ-H2AX and NFκB with an increased serum testosterone and catalase levels. These findings suggest that Zn and Se co-treatment could be a beneficial and protective option against BPA-exposed testicular and epididymal toxicity. [ABSTRACT FROM AUTHOR]

Swyer syndrome is a rare genetic disorder in which gonadal dysgenesis and karyotype 46, XY are observed. In the postnatal and prepubescent period, this disease has no clinical manifestations and is asymptomatic, which makes diagnosis difficult. The first signs of the syndrome appear in puberty in the form of underdevelopment of secondary sexual characteristics. This review presents the criteria based on which such a diagnosis as Swyer syndrome can be made. The main diagnostic methods are highlighted, the possibilities of both surgical treatment of patients and drug treatment due to hormone replacement therapy are considered. Verification of the syndrome contributes to a more thorough examination, which will allow you to determine management tactics and avoid complications from other organs and systems.

Abstract Background Sex chromosome abnormalities associated with disorders of sexual development (DSD) are rarely described in cats, mainly due to the lack of chromossome studies that precisely reveal the condition. Genetic approaches are therefore required in order to detect sex chromossomes abnormalities as variations in the number and structure of chromosomes, or the presence of a second cell line as mosaicim or chimerism. Case presentation A male Shorthair cryptorchid cat was presented with clinical signs of anorexia, tenesmus and hyperthermia. Ultrasonography revealed a fluid-filled structure, with approximately 1 cm in diameter, adjacent to the descending colon. Computed tomography evidenced a tubular structure, ventral to the descending colon and caudal to the bladder, which extended cranially, through two branches. Histopathological evaluation confirmed the presence of two atrophic uterine horns and one hypoplastic testicle with epididymis at the end of one of the uterine horns. The end of the other uterine horn was attached to a structure composed by a mass of adipocytes. Cytogenetic analysis revealed a mosaic 37,X/38,XY karyotype. The two cell lines were found in 15% and 85% of the lymphocytes, respectively. Genetic analysis confirmed the presence of SRY and ZFY genes in blood and hair bulbs, and revealed a marked reduction in SRY expression in the testicle. Additionally, this case presented exceptionally rare features, such as a Leydig’ cell tumour and a chronic endometritis in both uterine horns. Conclusions Complete imaging workup, cytogenetic analysis and SRY gene expression should be systematically realized, in order to properly classify disorders of sexual development (DSD) in cats.

Key Clinical Message: A comprehensive diagnostic approach is crucial for patients with primary amenorrhea and short stature. Karyotyping and imaging studies help to detect hidden chromosomal abnormalities and anatomical differences, emphasizing their value in this context. A 16‐year‐old girl with absent menstruation and short stature. Further examination revealed constitutional stunting and primary amenorrhea. Karyotyping revealed a 46, XY chromosomal abnormality, whereas pelvic ultrasonography showed uterine hypoplasia and a unicornuate uterus with a rudimentary horn. After 11 months of therapy, she experienced menarche and improved secondary sexual characteristics. [ABSTRACT FROM AUTHOR]

This article discusses a case of complete androgen insensitivity syndrome (CAIS) combined with bilateral inguinal hernia. CAIS is a rare genetic disorder that results in a complete loss of androgen receptor function, leading to the presence of exclusively female sexual characteristics in individuals with a 46, XY chromosome karyotype. Inguinal hernia is a common condition, and it has been found to be prevalent in over 50% of patients with CAIS. The article presents the case of a patient with CAIS and bilateral inguinal hernia, highlighting the challenges in diagnosis and treatment. The patient underwent laparoscopic surgery to repair the hernias and excise suspected gonadal tissue. Pathological examination confirmed the presence of atrophied testicular tissue, vas deferens, and epididymis, consistent with cryptorchidism. The article emphasizes the importance of accurate diagnosis and appropriate treatment for similar patients. [Extracted from the article]

Background: Sex chromosome abnormalities associated with disorders of sexual development (DSD) are rarely described in cats, mainly due to the lack of chromossome studies that precisely reveal the condition. Genetic approaches are therefore required in order to detect sex chromossomes abnormalities as variations in the number and structure of chromosomes, or the presence of a second cell line as mosaicim or chimerism. Case presentation: A male Shorthair cryptorchid cat was presented with clinical signs of anorexia, tenesmus and hyperthermia. Ultrasonography revealed a fluid-filled structure, with approximately 1 cm in diameter, adjacent to the descending colon. Computed tomography evidenced a tubular structure, ventral to the descending colon and caudal to the bladder, which extended cranially, through two branches. Histopathological evaluation confirmed the presence of two atrophic uterine horns and one hypoplastic testicle with epididymis at the end of one of the uterine horns. The end of the other uterine horn was attached to a structure composed by a mass of adipocytes. Cytogenetic analysis revealed a mosaic 37,X/38,XY karyotype. The two cell lines were found in 15% and 85% of the lymphocytes, respectively. Genetic analysis confirmed the presence of SRY and ZFY genes in blood and hair bulbs, and revealed a marked reduction in SRY expression in the testicle. Additionally, this case presented exceptionally rare features, such as a Leydig' cell tumour and a chronic endometritis in both uterine horns. Conclusions: Complete imaging workup, cytogenetic analysis and SRY gene expression should be systematically realized, in order to properly classify disorders of sexual development (DSD) in cats. [ABSTRACT FROM AUTHOR]

Turner syndrome is one of the most frequent chromosomal disorders and has an increased associated morbidity. The clinical picture of Turner syndrome reveals itself gradually, not every patient exhibits the full clinical picture, but gonadal dysgenesis and short stature are invariably present. We describe the long-term outcomes in a cohort of 41 patients with Turner syndrome followed at the Regional Center for Medical Genetics Bihor. A retrospective study was performed using the medical records; epidemiological, clinical, laboratory, cytogenetic, and imaging data were analyzed. The frequency of congenital heart abnormalities and intellectual disability was increased in the study group, necessitating a more effective screening technique in our country, to identify all the cases with TS. Early diagnosis and hormonal treatment are critical for a patient's favorable prognosis in stature, bone metabolism, cardiovascular system, and quality of life. Patients with TS have higher rates of related morbidity, especially skeletal, kidney, ophthalmological, and dermatological and a multidisciplinary team is essential for the management of TS cases. [ABSTRACT FROM AUTHOR]

Testicular malignancies commonly affect adolescent and young adult males. Although they tend to respond well to cisplatin-based chemotherapy with excellent overall survival, complications such as inferior vena cava tumor thrombus are rare and can be associated with high morbidity and mortality. We present a case of tumor thrombus in a 21-year-old active duty male with a newly diagnosed stage IIIB non-seminomatous germ cell tumor presenting with extensive left lower extremity swelling. Ultrasound with Doppler was notable for significant thrombus of the left common femoral, femoral, and popliteal vein. Computed tomography imaging revealed extensive thrombus of the inferior vena cava, left iliac veins, and left gonadal vein with sparing of the left renal vein. Endovascular thrombectomy was performed with pathologic analysis confirming the presence of malignant cells consistent with tumor thrombus. The patient continued subsequent non-seminomatous germ cell tumor treatment without complications. [ABSTRACT FROM AUTHOR]

Purpose: Sinonasal nuclear protein in testis carcinoma (SNUTC) is a rare, aggressive malignancy caused by genetic rearrangements in the NUTM1 gene. The prognosis of SNUTC ranks among the most unfavorable within the naso-sinusal district, with an overall survival of 9.7 months. This systematic review aimed to determine the best therapeutic strategy for SNUTC. Methods: We reviewed eligible articles for patient demographics, TNM and stage at presentation, best response after primary treatment, disease-free survival and overall survival (OS) times, other following therapy lines, and final outcomes. Results: Among 472 unique citations, 17 studies were considered eligible, with reported treatment data for 25 patients. Most studies (n = 12) were case reports. The most frequently administered treatment regimen was surgery as primary treatment and combined radiochemotherapy as second-line or adjuvant treatment. Four patients were alive at follow-up. Conclusion: Basing on the existing literature, a standardized line in the treatment of SNUTC is not yet well delineated. A self-personalized strategy of therapy should be drawn on each patient affected by SNUTC. [ABSTRACT FROM AUTHOR]

Aims: The present aim was to evaluate vertical cephalometric characteristics in populations with Turner syndrome (TS) using meta‐analysis methodology. Methods: Six electronic databases were queried, up to August 2023, to identify studies comparing the vertical cephalometric characteristics in populations with TS, compared to female control groups. Data were extracted from eligible studies and random‐effects meta‐analysis was employed. Subgroup meta‐analyses for age and karyotype were also attempted. Risk of bias was assessed using a modified version of the AXIS tool. Results: From the initial 195 studies identified, 17 were included in the quantitative synthesis, resulting in a sample of 417 patients with TS, originating from 10 different countries. Risk of bias was overall questionable. Mandibular ramus height was found to be smaller in females with TS, along with a reduction in posterior facial height, a larger anterior‐posterior facial height ratio, and an increase in the mandibular plane angle. Subgroup meta‐analyses showed that females with the monosomy X karyotype had vertical cephalometric characteristics which deviated more from the norm than those with other karyotypes. Conclusion: The vertical lateral cephalometric characteristics of females with TS differ significantly from those of non‐syndromic females, with the largest and most consistent deviation being seen in the monosomy X karyotype. Females with TS show less craniofacial posterior vertical development, with an evident reduction in mandibular ramus height leading to the cephalometric characteristics observed. [ABSTRACT FROM AUTHOR]

The term 'differences of sex development' (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, and/or anatomical sex. DSD in individuals with a 46,XX karyotype can occur due to fetal or postnatal exposure to elevated amount of androgens or maldevelopment of internal genitalia. Clinical phenotype could be quite variable and for this reason these conditions could be diagnosed at birth, in newborns with atypical genitalia, but also even later in life, due to progressive virilization during adolescence, or pubertal delay. Understand the physiological development and the molecular bases of gonadal and adrenal structures is crucial to determine the diagnosis and best management and treatment for these patients. The most common cause of DSD in 46,XX newborns is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, determining primary adrenal insufficiency and androgen excess. In this review we will focus on the other rare causes of 46,XX DSD, outside CAH, summarizing the most relevant data on genetic, clinical aspects, puberty and fertility outcomes of these rare diseases. [ABSTRACT FROM AUTHOR]

OMIM 273750 (3-M) syndrome is a rare cause of severe short stature with variable dysmorphic features caused by pathogenic variants in several genes including cullin7 gene (CUL7). Hypogonadism and hypospadias have been described in only a few males. We report a patient with CUL 7 pathogenic variant who had bifid scrotum and perineal hypospadias at birth. He entered puberty spontaneously at age 12 years and appropriately completed pubertal development by 15 years. Subsequently, a regression of testicular volumes, increased gonadotropin levels, and reduced (although normal) testosterone levels were observed. This case highlights the importance of careful pubertal monitoring as pubertal dysfunction may be associated with 3-M syndrome. [ABSTRACT FROM AUTHOR]

Problem: The luteinizing hormone (LH), produced by gonadal and nongonadal cells in the anterior pituitary gland play a critical role in human sexual development and reproduction. It is required for the induction of ovulation in females and sex steroid hormone production in both males and females. It is also an important player in early pregnancy events in oviducts and in absence of LH signalling, the uterus cannot initiate pregnancy. LH works through its receptor LHCGR. Therefore, it is quite important to figure out those mutations that have the potential to affect the structure and function of both LH and LHR. Materials and Methods: Various in silico tools were employed in the study for the data mining of SNPs and predicting their possible impact on the structure and function of the protein. ConSurf analysis predicted V454I and I161K are exposed residues in the 2D structure of protein and highly conserved in protein structure. PSIPRED and Swiss Modeller were employed to predict the 2D and 3D structure of mutated receptor protein. FT site server predicted both substitutions were involved in the ligand‐binding site Results: By present analysis, we have found that R59G in LHα, Q74R and T78N in LHβ and V454I and I161K in LHCGR are the most deleterious nsSNPs affecting the structure and function of the protein. Conclusion: These SNPs are still uncharacterised; hence providing a baseline for validation of their association with the susceptibility of diseases and develop personalised therapeutics. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed at integrating the clinical and phenotypic characteristics, hormonal profile and genetic diagnosis of children with malformation syndromes associated with XY disorders of sex development (DSD) in a single-center in Egypt. Methods: This retrospective study included patients with syndromic XY DSD recruited from the Pediatric Endocrinology and Surgery units at Alexandria University Children's Hospital (AUCH), Alexandria, Egypt, between 2018 and 2023. All patients included in the study underwent a detailed clinical and laboratory evaluation, ultrasonography (and laparoscopy if needed). Results: The study included 30 children with syndromic XY DSD; most of these children were diagnosed at birth. The most common extragenital malformations included skeletal anomalies (70%), facial dysmorphism (46.7%), cerebral malformations (30%) and congenital heart disease (23.3%). Ventricular septal defect was the most common congenital heart disease. Conclusion: Integration between clinical, laboratory and genetic data is the cornerstone in the management of XY DSD patients for appropriate decision making of surgical intervention and sex assignment, in addition to screening for other associated features of each mutation. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of male differences of sex development is a challenging multidisciplinary team task, that requires external genital evaluation, karyotyping, hormonal profiling, radiological work up and frequently diagnostic laparoscopy and biopsy, for evaluation of internal duct system and nature of gonads. The debate still persists regarding the best diagnostic modality for accurate visualization of Müllerian duct remnants (MDRs) in those patients. The aim of the study was to compare between laparoscopy (L) and ultrasonography (US) regarding the diagnostic accuracy in detection of Müllerian duct remnants, in addition to describing their anatomical nature and relations with the male duct system, in patients with male DSD, with various karyotypes. Methods: We prospectively included 20 patients with male DSD, mostly due to 46 XY DSD or chromosomal DSD, over 2 years. The medical and radiological data were collected and analyzed. Results: The age at the first diagnostic intervention ranged from 8 to 24 months (mean: 17 months). There were 14 patients with 46XY DSD with variable diagnoses (3 ovotesticular DSD, 3 partial gonadal dysgenesis, 6 persistent Müllerian duct remnants syndrome and 2 mixed gonadal dysgenesis). Two patients with 46XX DSD were included (one XX male, and one patient with ovotesticular DSD). One patient with chimerism (46XY/46XX) and three patients with 46XY/45XO mixed gonadal dysgenesis were also recruited. MDRs were evident in all cases (100%) by laparoscopy, only 25% (n = 5) were visualized by US. There was a statistically significant difference between laparoscopy and US regarding gonadal and MDR visualization, being higher with laparoscopy (p values, 0.0180 and 0.001). Conclusions: Ultrasonography failed to visualize Müllerian remnants in 75% of patients with complex DSD. On the other hand, laparoscopy provided optimum visualization of MDRs and gonads in those children. [ABSTRACT FROM AUTHOR]