Disorders Of Sexual Differentiation Research Articles

8610 The Role of Adenylyl Cyclase 2 Gene-Dosage Changes in Congenital Male Genitourinary Anomalies

Abstract Disclosure: D.J. Lamb: Advisory Board Member; Self; Ro Health, Inc. Stock Owner; Self; Fellow Health, Inc. M.A. O'Neill: None. Collectively, congenital genitourinary (GU) birth defects are the most common birth defects in males, yet relatively little is known about their cause. In part, this reflects the current clinical perspective that, because most of these birth defects can be surgically repaired, there is nothing to be gained by understanding the cause. Yet our studies show that seemingly simple birth defects like hypospadias or cryptorchidism, may be associated with other more significant underappreciated defects, such as those affecting the kidney, heart, eyes or behavior. We tested the hypothesis that chromosome microdeletions and microduplications (called copy number variations, CNVs) result in gene-dosage changes that are important regulators of GU development and when haploinsufficient or duplicated normal genitourinary development is impacted causing birth defects of the upper and/or lower genitourinary tract. We successfully used this strategy to identify 15 different previously unrecognized genes that when microduplicated or microdeleted result in conditions such as cryptorchidism, hypospadias, disorders of sexual differentiation (DSD) and other anomalies. Remarkably, gene-dosage changes affected major signaling pathways and post-translational modifications in novel, previously unrecognized ways. Herein, we focused on defining the role of a candidate gene commonly microdeleted or microduplicated in patients with cryptorchidism, hypospadias and/or micropenis. Locus mapping allowed identification of adenylate cyclase 2 (ADCY2) as a candidate gene at the 5p15.31 Cri-du-Chat region in patients with male genital tract anomalies. ADCY2 CNVs were more common in non-syndromic patients with micropenis, cryptorchidism, and/or hypospadias (1.6%) than the general population (0.07%; p< 0.001). Whole exome sequence studies revealed a range of phenotypic anomalies in patients with damaging and potentially damaging ADCY2 variants in addition to the male GU anomalies, including congenital anomalies of the kidney and urinary tract. It is our hypothesis that ADCY2 duplications result in a de-sensitization of the LH receptor diminishing testosterone biosynthesis in the testis, whereas deletions diminish LH receptor signaling. ADCY2 CNVs were assessed in 100 men with spermatogenic failure who were born with cryptorchidism. The ADCY2 CNV frequency was the same as in our cohort of boys with GU anomalies, but as adults they also have hypergonadotropic hypogonadism, which we predicted if ADCY2 over-expression was impacting adult Leydig cell steroidogenesis through partial desensitization of the LH receptor. These studies identified an unrecognized cause of GU anomalies. In the future, such knowledge may lead to improved diagnosis and therapeutic approaches to ameliorate these common birth defects. Presentation: 6/2/2024

De La Chapelle Syndrome: Clinical and Physical Performance Implications

Gynecomastia in adolescence is a benign condition that mostly disappears spontaneously within approximately two years from onset. When it is associated with hypogonadism, it may suggest a disorder of sexual differentiation. We report the case of a young man (18 years old) with gynecomastia associated with azoospermia, small testes, hyperestrogenism and hypergonadotropic hypogonadism. A karyotype 46,XX was found, and searching for SRY (sex-determining region Y) by fluorescence in situ hybridization (FISH) highlighted the presence of the gene on the terminal region of the short arm, with breakpoints likely in Xp22.3 and Yp11.3. Implications of testosterone replacement therapy with respect to sex differentiation disorder and to physical performance are discussed.

Clinical, Genetic, Biochemical, Hormonal, and Radiological Profile in Patients with Disorders of Sex Development Presenting at a Tertiary Care Center in Central India

Abstract Introduction: Disorders of sexual differentiation or differences in sex development (DSD) is a congenital anomaly with abnormal differentiation between internal gonads and external genitalia. We present the clinical, genetic, biochemical, hormonal, and radiological profile of DSD patients who presented at a tertiary care institute in Chhattisgarh during 2 years. Methodology: All patients with DSD and age <18 years who presented in the Outpatient Department of Pediatrics and Pediatric Surgery between January 2022 and December 2023 (2 years) in All India Institute of Medical Sciences, Raipur, Chhattisgarh, were included in this study. Our aim was to study the clinical, genetic, biochemical, hormonal, and radiological profile of patients with DSD presenting at our institute to outline the management plan in these patients. Results: During the study period, there were seven patients with DSD; with age ranging from 1 year to 15 years. Four patients presented in adolescent age. There were two patients with XXDSD – diagnosed to have classic congenital adrenal hyperplasia (21-hydroxylase deficiency). There was one patient with XYDSD – androgen insensitivity. Four patients had ovotesticular DSD – two had pure gonadal dysgenesis and two had mixed gonadal dysgenesis. Four patients needed gender reassignment. Conclusion: Patients with DSD require a systematic management at a tertiary care center. Assigning the sex of rearing should be done only after proper workup of patients and arriving at a diagnosis. Proper counseling of parents and individualized management as per the Indian Association of Pediatric Surgeons guidelines is mandatory.

Laparoscopy versus ultrasonography for the evaluation of Müllerian duct remnants in male patients with disorder of sex differentiation

BackgroundThe 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.MethodsWe 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.ResultsThe 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).ConclusionsUltrasonography 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.

Genetic diagnosis of endocrine disorders in Cyprus through the Cyprus Institute of Neurology and Genetics: an ENDO-ERN Reference Center

The report covers the current and past activities of the department Molecular Genetics-Function and Therapy (MGFT) at the Cyprus Institute of Neurology and Genetics (CING), an affiliated Reference Center for the European Reference Network on Rare Endocrine Conditions (Endo-ERN).The presented data is the outcome of > 15 years long standing collaboration between MGFT and endocrine specialists from the local government hospitals and the private sector. Up-to-date > 2000 genetic tests have been performed for the diagnosis of inherited rare endocrine disorders. The major clinical entities included Congenital Adrenal Hyperplasia (CAH) due to pathogenic variants in CYP21A2 gene and Multiple Endocrine Neoplasia (MEN) type 2 due to pathogenic variants in the RET proto-oncogene. Other rare and novel pathogenic variants in ANOS1, WDR11, FGFR1, RNF216, and CHD7 genes were also found in patients with Congenital Hypogonadotropic Hypogonadism. Interestingly, a few patients with Disorders of Sexual Differentiation (DSD) shared rare pathogenic variants in the SRD5A2, HSD17B3 and HSD3B2 while patients with Glucose and Insulin Homeostasis carried theirs in GCK and HNF1A genes. Lastly, MGFT over the last few years has established an esteemed diagnostic and research program on premature puberty with emphasis on the implication of MKRN3 gene on the onset of the disease and the identification of other prognosis biomarkers.As an Endo-ERN member MGFT department belongs to this large European network and holds the same humanistic ideals which aim toward the improvements of health care for patients with rare endocrine conditions in respect to improved and faster diagnosis.

Pregnancy outcomes with undescended testis husbands: influenced by wive’s life style and surgical correction before 1 year

Background The most prevalent sexual differentiation disorder in males is undescended testis (UDT), which occurs when the testis is absent from the scrotum or cannot be brought down during a physical examination. Pregnancy outcome may be influenced by the wife’s lifestyle and surgical correction within the past year
 Objectives This study aims to determine pregnancy outcome in Assisted Reproductive Technology (ART) on a wive with a UDT husband assessed by the wive’s life style and surgery correction before 1 year.
 Methods A cross-sectional study was conducted. Data were taken from patients who underwent Assisted Reproductive Technology at AMC Hospital, Yogyakarta. Data collection from 2018 to 2021. Samples in the unilateral and bilateral groups were 20 husbands. Wilcoxon Signed Rank Test helped carry out the analyses.
 Results There was an association between infertility and UDT either unilaterally or bilaterally (p = 0.009). Most UDT husbands had a BMI in the overweight category and the average age was 28 and 29. Other factors such as the wive’s life style and surgery correction before 1 year , including smoking habit, alcohol consumption, addictive drug and hormonal drug, had no significant effect on the success of pregnancy outcome (p > 0.05).
 Conclusions Although pregnancy outcome in unilateral and bilateral UDT patients was not statistically significant, clinically, the pregnancy outcome was better in husbands with unilateral UDT by IUI than in IVF.
 Bangladesh Journal of Medical Science Vol. 23 No. 02 April’24 Page : 455-462

Androgen insensitivity syndrome: preventive gonadectomy, pros and cons

Androgen insensitivity syndrome is a genetic disorder characterized by complete or partial androgen insensitivity in individuals with a 46XY genotype. It is also the most common cause of disorders of sexual differentiation in patients with a 46XY karyotype. This condition is caused by a defect in the androgen receptor gene (AR), leading to abnormal development of male genitalia, impaired formation of male secondary sexual characteristics, and phenotypic features resembling the female sex.One of the important aspects related to the management of androgen insensitivity syndrome is the necessity of preventive gonadectomy. However, the rationale for prophylactic removal of gonads remains a subject of debate. This article presents a clinical case of a 37-year-old woman with complete androgen insensitivity syndrome who, despite recommendations for gonadectomy based on suspicious MRI characteristics of the gonads, made the decision to decline surgical intervention, justifying her choice by the positive impact of gonadal hormonal activity on her external appearance and physical characteristics. This clinical case highlights the complexity of decision-making in the management of androgen insensitivity syndrome, where patient preferences and needs may play a significant role, despite potential risks and concerns surrounding the preservation of gonads.

Application of management algorithm to a series of patients of disorders of sexual differentiation from Southern India: A case series 

No abstract available

A Pilot Survey of Indian Stakeholders: Parents, Doctors, and Grown-Up Patients of Disorders of Sexual Differentiation on Management Decisions and Associated Gender Dysphoria.

Of late, there are many legal representations from select quarters to halt all medical interventions in children with differences of sex development (DSD). In this survey on management decisions in DSD, we distil the views of Indian stakeholders: parents, physicians, and grown-up patients with DSD on their management decisions to identify decisional satisfaction or gender dysphoria. The survey domains included the patient demographics, final diagnosis, decision on the sex of rearing, surgical interventions, opinion of the stakeholders on the preferred age of sex assignment, final sex of rearing, and agreement/disagreement about sex assignment (gender dysphoria). A total of 106 responses were recorded (66% parents, 34% grown-up patients aged 12-50 years). Among parents, 65/70 (95%) preferred the sex to be assigned soon after birth. All grown-up patients preferred sex to be assigned soon after birth. Regarding decisions on surgery, 74% of physicians and 75% of the grown-up patients felt parents should be allowed to decide interventions. Among Indian parents, 90% felt they should have the right to decide surgery in the best interest of their child for a safe social upbringing. Overall, gender dysphoria among Indian DSD patients was <1% (1/103, 0.97%). The predominant preference and opinion of major Indian stakeholders (physicians, parents, and grown-up DSD patients) support the existing approach toward DSD management, including early sex assignment and necessary medical intervention.

Molecular Diagnosis of Sexual Differentiation Disorders in Burkina Faso

Molecular Diagnosis of Sexual Differentiation Disorders in Burkina Faso

Complete or partial loss of the Y chromosome in an unselected cohort of 865 non-vasectomized, azoospermic men

BackgroundStructural abnormalities as well as minor variations of the Y chromosome may cause disorders of sex differentiation or, more frequently, azoospermia. This study aimed to determine the prevalence of loss of Y chromosome material within the spectrum ranging from small microdeletions in the azoospermia factor region (AZF) to complete loss of the Y chromosome in azoospermic men.ResultsEleven of 865 azoospermic men (1.3%) collected from 1997 to 2022 were found to have a karyotype including a 45,X cell line. Two had a pure 45,X karyotype and nine had a 45,X/46,XY mosaic karyotype. The AZF region, or part of it, was deleted in eight of the nine men with a structural abnormal Y-chromosome. Seven men had a karyotype with a structural abnormal Y chromosome in a non-mosaic form. In addition, Y chromosome microdeletions were found in 34 men with a structural normal Y chromosome. No congenital malformations were detected by echocardiography and ultrasonography of the kidneys of the 11 men with a 45,X mosaic or non-mosaic cell line.ConclusionsIn men with azoospermia, Y chromosome loss ranging from small microdeletions to complete loss of the Y chromosome was found in 6.1% (53/865). Partial AZFb microdeletions may give a milder testicular phenotype compared to complete AZFb microdeletions.

Disorders of sexual differentiation. A clinical case

The biological sex of a person is anatomical, physiological, and genetic features that help distinguish a male organism from a female one. One distinguishes genetic, gonadal, and phenotypic sex of a person. Sexual differentiation is a process of development, during which the biological male or female sex is formed, it occurs under the influence of genetic and hormonal factors during fetal development. In this regard, any damage at this stage can lead to disorder of sexual development of a newborn. Disorder of sexual differentiation is a complex of medical conditions in which there is a mismatch between a person’s genetic, gonadal and phenotypic sex.Sometimes it is difficult to visually determine the sex of a child born with disorder of the sexual development due to an abnormal, undefined structure of the external genitalia. For example, they may have the appearance of hypertrophied labia majora and/or a hypertrophied clitoris and the absence of testicles, or vice versa, the child’s genitals may have a normal appearance, but at the same time the internal genitals may be improperly developed.To determine which gender to choose for a child with disorder of sexual differentiation, a number of examinations, including genetic ones, should be carried out. Disorder of sexual differentiation is a complex medical and social problem involving a multidisciplinary team of doctors and the patient’s family. This article describes a clinical case of a child with disorder of sexual differentiation at the stage of diagnosis verification. An interdisciplinary approach is an integral part of accompanying a child with disorder of sexual differentiation, where the joint efforts of doctors, psychologists, teachers and other specialists contribute to the creation of inclusive and safe conditions for the development of each person.

An Unusual Clinical and Radiological Presentation of Ovotesticular Disorders of Sex Development with Male and Female External Genitalia: A Case Report

Background: Ovotesticular disorders of sex development (ODSD), previously known as true hermaphroditism, is a rare disorder of sexual differentiation that causes ambiguity in external genitalia and the presence of both ovarian and testicular elements in the gonads. The condition is characterised by the existence of testicular tissue with distinctive tubules and ovarian tissue in the same gonad (ovotestis), or separately in an individual. The most common cytogenetic karyotype is 46,XX. The age and presentation of symptoms vary, but typically include hypospadias, urogenital sinus, inguinal hernia, cryptorchidism, and gynaecomastia during the peripubertal age, as well as lower abdominal mass. Case Presentation: A 15-year-old female exhibited typical male genitalia, including a normal penile shaft, scrotal sac, palpable testes, and a urethral opening, with a separate vaginal opening located between the penile shaft and scrotum. Pelvic MRI confirmed the presence of both testes within the scrotal sac and an infantile-sized uterus with a central endometrium, as well as a left-sided ovary in the pelvic region. The right ovary was not seen. Correlative ultrasound confirmed these findings and indicated that the testes had a normal echo texture and vascularity. The patient was diagnosed with ODSD, and further hormonal testing was recommended. Conclusions: ODSD is a rare cause of genital ambiguity. Typically, both paramesonephric and mesonephric duct derivatives are seen, and most of the affected individuals present as neonates or infants with ambiguous external genitalia. At peripubertal age, the symptoms typically include hypospadias, urogenital sinus, inguinal hernia, unilateral or bilateral cryptorchidism, and gynaecomastia. Fertility is not uncommon and has been reported in female-reared patients. The ovotestis is the commonest gonad in people with ODSD and are known to be predisposed to germ cell tumours. Over 500 cases of ODSD have been reported in the literature. Ultrasound is the first line of investigation used to see the pelvic organs. The non-invasive test of choice for detecting paramesonephric and mesonephric duct derivatives is an MRI pelvis. The purpose of this paper is to describe various clinical and radiological features associated with ODSD.

(199) Anterolateral Thigh Flap Phalloplasty for Micropenis

Abstract Introduction Congenital micropenis is defined as a normally formed penis with a stretched penile length less than 2.5 standard deviations below the mean for that man’s age and ethnicity. Micropenis may present as an isolated condition or with other genital or multi-system abnormalities. Penile reconstruction or phalloplasty may be required where topical and systemic hormonal treatment have failed. The most common flap used for phalloplasty is the radial artery forearm free flap phalloplasty. Other alternatives include the anterolateral thigh (ALT), musculocutaneous latissimus dorsi and abdominal flaps. Objective The aim of this video is to illustrate the technique for penile reconstruction using a pedicled ALT flap without integrated urethra. Methods A 21-year-old man with micropenis and hypospadias from a disorder of sexual differentiation (46XY) presents for penile reconstruction following multiple failed attempts at hypospadias repair. He requested an ALT flap without integrated urethra because he is dependent on a long-term suprapubic catheter due to a hypocontractile bladder. Intraoperative vascular doppler identified 3 perforators from the descending branch of the lateral circumflex iliac artery of the left leg. The flap was designed centred on the perforators with dimensions of 14cm (length), 13cm (width at base) and 12cm (width at tip). The flap was raised carefully and transferred to the recipient groin. The neophallus was constructed and microsurgical anastomosis of the lateral cutaneous of the thigh to one of the dorsal penile nerves with 8/0 nylon was completed. The partially divided left vastus lateralis muscle was re-approximated and the skin edges drawn in and flattened. The left thigh was then resurfaced with a 14/1000 of an inch split-thickness skin graft from the contralateral thigh. All wounds were dressed. Results The man had an uneventful post-operative course with careful vascular monitoring, and he was discharged on day 10. He is currently awaiting glans-sculpting and will eventually proceed with insertion of an inflatable erectile device. Conclusions Penile reconstruction using an ALT flap can be offered to a well-informed and motivated man with a micropenis following appropriate assessment. As shown, the technique requires careful dissection of the perforator vessels and can usually be transferred as a pedicled flap. Pedicled flaps do not require microvascular anastomosis and therefore have a lower risk of vascular compromise. Further esthetic and functional refinements like the insertion of an erectile device are possible in later stages, if desired. Disclosure No

46 XY disorder of sex development: Case report

Disorders of sexual differentiation in 46, XY patients cover a wide spectrum of clinical pictures (female phenotype, posterior hypospadias, cryptorchidism). Their causes are varied and affect the stages of testicular determination (gonadal dysgenesis) or defects in testosterone production or action (testosterone secretion abnormalities, androgen insensitivity, 5⍺-reductase deficiency). They require rational and rapid management, within a multidisciplinary team. We report a rare case of this disorder in a patient of 18 years with the therapeutic obstacles that we faced in its management.

Anti-Müllerian hormone - clinical use and future possibilities.

Anti-Müllerian hormone (AMH) is a protein produced already in human fetus. It has an essential role in the differentiation of the reproductive tract, regulation of the ovaries and testes. The determination of serum AMH levels is used in clinical practice. Today, especially in reproductive medicine in the assessment of ovarian reserve and in the prediction of the response to ovarian stimulation. However, in young cancer patients, it can also predict the risk of ovarian failure after anticancer treatment. It finds further use in pediatric endocrinology in the diagnosis of sexual differentiation disorders. In oncology, it is used as a tumor marker for monitoring patients with granulosa tumors. In the future, however, it is also promising to use the knowledge of AMH function for the treatment of gynecological as well as other solid malignancies expressing a tissue-specific receptor for AMH.

V11-03 PENILE RECONSTRUCTION FOR CONGENITAL MICROPENIS WITH THE ANTEROLATERAL THIGH PEDICLED FLAP

You have accessJournal of UrologyCME1 Apr 2023V11-03 PENILE RECONSTRUCTION FOR CONGENITAL MICROPENIS WITH THE ANTEROLATERAL THIGH PEDICLED FLAP Aurélie Schirmann, Nim Christopher, David Ralph, and Wai Gin Lee Aurélie SchirmannAurélie Schirmann More articles by this author , Nim ChristopherNim Christopher More articles by this author , David RalphDavid Ralph More articles by this author , and Wai Gin LeeWai Gin Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003337.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Congenital micropenis is defined as a normally formed penis with a stretched penile length less than 2.5 standard deviations below the mean for that man’s age and ethnicity. Micropenis may present as an isolated condition or with other genital or multi-system abnormalities. Penile reconstruction or phalloplasty may be required where topical and systemic hormonal treatment have failed. The most common flap used for phalloplasty is the radial artery forearm free flap phalloplasty. Other alternatives include the anterolateral thigh (ALT), musculocutaneous latissimus dorsi and abdominal flaps.The aim of this video is to illustrate the technique for penile reconstruction using a pedicled ALT flap without integrated urethra. METHODS: A 21-year-old man with micropenis and hypospadias from a disorder of sexual differentiation (46XY) presents for penile reconstruction following multiple failed attempts at hypospadias repair. He requested an ALT flap without integrated urethra because he is dependent on a long-term suprapubic catheter due to a hypocontractile bladder.Intraoperative vascular doppler identified 3 perforators from the descending branch of the lateral circumflex iliac artery of the left leg. The flap was designed centred on the perforators with dimensions of 14cm (length), 13cm (width at base) and 12cm (width at tip). The flap was raised carefully and transferred to the recipient groin. The neophallus was constructed and microsurgical anastomosis of the lateral cutaneous of the thigh to one of the dorsal penile nerves with 8/0 nylon was completed. The partially divided left vastus lateralis muscle was re-approximated and the skin edges drawn in and flattened. The left thigh was then resurfaced with a 14/1000 of an inch split-thickness skin graft from the contralateral thigh. All wounds were dressed. RESULTS: The man had an uneventful post-operative course with careful vascular monitoring, and he was discharged on day 10. He is currently awaiting glans-sculpting and will eventually proceed with insertion of an inflatable erectile device. CONCLUSIONS: Penile reconstruction using an ALT flap can be offered to a well-informed and motivated man with a micropenis following appropriate assessment. As shown, the technique requires careful dissection of the perforator vessels and can usually be transferred as a pedicled flap. Pedicled flaps do not require microvascular anastomosis and therefore have a lower risk of vascular compromise. Further aesthetic and functional refinements like the insertion of an erectile device are possible in later stages, if desired. Source of Funding: None declared © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e999 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aurélie Schirmann More articles by this author Nim Christopher More articles by this author David Ralph More articles by this author Wai Gin Lee More articles by this author Expand All Advertisement PDF downloadLoading ...

A 10-YEAR STUDY OF CHILDREN WITH GONADAL TUMORS AND DISORDERS OF SEX DIFFERENTIATION, IN ROMANIA.

Children having gonadal tumors and disorder of sex differentiation (DSD) are rare. To investigate the presentation of DSD children with malignant gonadal tumors. A retrospective study from 2010-2020, that evaluated 17 children with DSD, including 13 females, eight months to 16 years, with congenital adrenal hyperplasia, 5-alpha reductase deficiency, androgen insensitivity syndrome, Turner, Sywer, and Klinefelter syndromes. Ten children had malignant gonadal tumor; nine had germ cell tumors and one person granulosa cell tumors, while seven children with non-malignant tumor had gonadoblastoma, cystadenoma (five children), and cysts. Systemic malformations, obesity, elevated tumor markers, and psychosocial issues were observed in 90%, 90%, 70%, and 50% of children with malignancy unlike 28.6%, 42.9%, 14.35%, and 57.1% children without malignancy respectively. Most (9/10) children >12 years, had psychosocial issues, unlike 0/7 children ≤12 years. From 8/17 children presenting with symptoms suggestive of tumor, 75% had malignancy, while from 9/17 children with DSD presentation, 44% had malignant tumors. Malignancy was observed in 3/10 children between eight months to age six, while 7/10 children had stage 1-2 tumors. We reported a child, identified as female, aged 13 years, with partial androgen insensivity syndrome (PAIS) 46,XY, and testicular papillary serous cystadenoma with genomic variant AR NM_000044.4:c.2750del. p.(F917Sfs*27) chromosome Xq12, never published in people with PAIS nor population databases (GnomAD). DSD diagnosis raises numerous challenges. People with DSD have increased risk of malignancy, especially when obesity and, systemic malformations are present; also, psychosocial issues in these children are associated with postpubertal age.

Prevalence, distribution, and risk markers for the development of gonadal germ cell tumors in patients with certain types of disorders of sexual differentiation with Y chromosome - A retrospective study.

To study the prevalence, subtypes, and risk markers for the development of gonadal germ cell tumors (GCT's) among disorders of sexual differentiation (DSD) patients with the Y chromosome. Design: A retrospective review of the patient's case records from 2010 to 2020 in Government Medical College, Thiruvananthapuram, India was studied. The study participants included 54 subjects with DSD containing the Y chromosome. Demographic data, external masculinization scoring, associated congenital anomalies, karyotyping, intraoperative findings such as gonadal location and internal genital ducts, histopathology of the resected gonads, and its immunohistochemistry were collected. The prevalence of gonadal GCT's was estimated from paraffin-embedded gonadectomy samples (S = 82). The median age of occurrence of gonadal GCT's was 18 years. The prevalence of malignant gonadal GCT's was highest among the PAIS group (19.2%) followed by gonadal dysgenesis (15.8% each in MGD and CGD) and least among CAIS (7.7%) (p < 0.01). The most common type of malignant gonadal GCT's in the descending order of frequency was dysgerminoma, seminoma, mixed GCT, and yolk sac tumor. Multivariance logistic analysis showed post-puberty and the presence of congenital anomalies were associated with the occurrence of gonadal GCT's ( P < 0.01). The overall prevalence of gonadal GCT's (malignant and premalignant) among DSD with Y chromosomes is nearly 25%. Dysgerminoma is the most common malignant gonadal GCT's. Age at or above 18 years and the presence of congenital anomalies like renal agenesis, retroperitoneal vascular defects, and congenital diaphragmatic hernia were independent risk markers for the development of gonadal GCT's.

Posterior Sagittal Approach for Nonanorectal Malformation: Widening Spectrum.

Posterior sagittal is a very well accepted approach in the treatment of anorectal malformations. This approach provides good access and exposure through the perineum to the deep pelvic structures. It reduces risk of injury to important structures as dissection remains in midline. To access feasibility of posterior sagittal approach for non-anorectal malformation indications and to widen the spectrum. We present a series of 10 cases of non-anorectal malformations operated by this approach for 4 years. Six patients included in the study were of Disorders of Sexual Differentiation with pseudovagina, three of Y duplication of the urethra, and one of cervical atresia. All patients had good results. Posterior sagittal approach is feasible, safe with minimal bleeding, and no postoperative incontinence. It can safely be used for non-anorectal indications.