Disorders Of Sexual Differentiation Research Articles

A rare form of persistent Mullerian duct syndrome: Transverse testicular ectopia with germ cell testis cancer and hernia uteri inguinalis

Persistent Mullerian duct syndrome is a rare form disorder of sexual differentiation characterised by the persistence of Mullerian derivatives (fallopian tubes, uterus and the proximal vagina) in males with an XY karyotype and normal virilisation. We report a case of a 29-year-old man with right transverse testicular ectopia, mix germ cell cancer at ectopic right testis and left-sided obstructed inguinal hernia containing a uterus and fallopian tube. We performed orchiectomy and hysterectomy on the patient.

PD15-01 KANK1 GENETIC AND GENOMIC ANOMALIES AFFECT GENITOURINARY (GU) DEVELOPMENT IN HUMANS

You have accessJournal of UrologyPediatric Urology I (PD15)1 Sep 2021PD15-01 KANK1 GENETIC AND GENOMIC ANOMALIES AFFECT GENITOURINARY (GU) DEVELOPMENT IN HUMANS Marisol O'Neill, and Dolores Lamb Marisol O'NeillMarisol O'Neill More articles by this author , and Dolores LambDolores Lamb More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001997.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 9p24.3 is a chromosome hotspot for human GU anomalies with micro-deletions or -duplications associated with ambiguous genitalia and gonadal dysgenesis. One gene in 9p24.3, DMRT1, is needed for normal testicular fetal development. Using array comparative genomic hybridization (aCGH) together with retrospective literature/database analysis, locus mapping identified 60 patients with 9p24.3 CNVs of 37 duplications and 23 microdeletions. 50 of these patients had disorders of sexual differentiation, 7 had congenital anomalies of the kidney and urinary tract (CAKUT). We identified a second gene candidate in the minimal overlap region of 9p24.3 5' to DMRT1 that encompasses KN Motif and Ankyrin Repeat Domain Containing Protein 1 (KANK1). We used human and mouse models to test the hypothesis that genetic and genomic defects of KANK1 also resulted in anomalies of the external genitalia and CAKUT. METHODS: A mouse model of haploinsufficiency was generated using CRISPR-Cas9 to delete Kank1 and mice phenotyped. Penile and renal anomalies were defined by micro-CT analysis. Patients with upper and lower tract genitourinary birth defects underwent phenotypic analysis, genetic and genomic analysis by aCGH and whole exome sequencing. RESULTS: A mouse model of Kank1 haploinsufficiency exhibited renal dysfunction, penile anomalies and subfertility. KANK1 genetic variants were identified by Whole Exome Sequencing (WES) in patients with GU anomalies-2 had novel variants; one individual with an absent cervix, vaginal atresia and two novel variants resulting in nonsynonymous changes of two consecutive amino acids (p.C1187F and p.N118Y) both predicted to be deleterious. 14 individuals were identified with 10 rare variants, five of which (rs61737971, rs148744436, rs143675911, rs74458120, rs370051574) were present in individuals with CAKUT, renal insufficiency, focal segmental glomerulosclerosis, abnormal reproductive track development, hypospadias, bladder exstrophy- glomerular fibrosis, renal dysfunction, penile anomalies were also present in the Kank1 haploinsufficient mouse models. CONCLUSIONS: This study identifies a novel mechanism that underlies some GU birth defects which are usually surgically repaired with the etiology defined as idiopathic. This study identified renal dysfunction and a potentially severe kidney phenotype, as well as developmental anomalies of the penis caused by KANK1 haploinsufficiency in humans & mouse models. Source of Funding: T32 DK007763 (MO was a trainee) & R01DK078121 from NIDDK & Frederick J. and Theresa Dow Wallace Fund of the NY Community Trust (awarded to DJL) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e272-e272 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marisol O'Neill More articles by this author Dolores Lamb More articles by this author Expand All Advertisement Loading ...

The influence of sports policies on the right to fair competition for women

PurposeCompetitions in high-performance sports are based on the premise of fairness and the absence of advantages for participants. Therefore, several metrics were created to divide participants into categories and neutralize the advantages of some athletes. The division by sex is justified in the face of differences in body development between men and women due to testosterone levels. Faced with the difficulties of determining a single unequivocal criterion for determining sex, major sports entities periodically change the rules that guide the inclusion criteria to compete in the female category. The purpose of this study is to assess whether changes in gender metric rules bring female sports performance closer to male performance, reducing the equality of conditions for female competitors.Design/methodology/approachThis is a retrospective study that compared female and male results from the past 5 Olympic games in the 100-metre dash, high jump and javelin throw.FindingsThe performance in the men's category in the 100-metre dash was superior to the women's in the Olympic Games in Sydney by 8.78% (± 0.16), in Athens by 9.88% (± 0.21), in Beijing by 10.11% (± 0.29), in London by 9.25% (± 0.59) and in Rio de Janeiro by 8.6% (± 0.23). The male high jump was higher than the female by 17.24% (± 1.18) in Sydney, 16.61% (± 1.83) in Athens, 17.01% (± 1.79) in Beijing, 15.47% (± 1.96 higher) in London and 19.67% (± 1.09) in Rio de Janeiro. In the javelin throw, the male superiority was 34.87% (± 2.35) in Sydney, 29.88% (± 4.15) in Athens, 31.87% (± 4.15) in Beijing, 29.44% (± 3.24) in London and 32.31% (± 2.69) in Rio de Janeiro.Research limitations/implicationsAs limitations of the study, this study mentions the lack of hormonal dosage of the athletes involved, the non-evaluation of other modalities with different dynamics of execution and muscular requirements and the non-evaluation of the rules in sexual metrics during the qualifying stages for the games.Practical implicationsIn this manuscript, the authors show that interference of the International Olympic Committee in the sex metric influences the athletic performance of women in some sports. Rules that facilitate participation of transgender athletes, or with sexual differentiation disorder and other forms of hyperandrogenism, improve female athletic performance overall.Originality/valueThe authors believe that this manuscript is appropriate for publication by International Journal of Human Rights in Healthcare because it is an original paper that fits the goals of the publication. This manuscript creates a paradigm for future policies that rule the sex determination metrics in competitive sports.

A rare case of male sex reversal syndrome (46, XX) with negative SRY gene: a disorder of sexual differentiation (DSD)

BackgroundMale sex reversal syndrome is a rare genetic cause of male infertility with an overall incidence of 1/20,000–1/100,000 males. There is mismatching between the genetic make-up and the apparent clinical features. The clinical presentation of such cases is variable ranging from ambiguous genitalia at birth, failed puberty, up to normal male phenotype with infertility and hypogonadism. The exact molecular and genetic bases of this syndrome are still unclear. Most of the recorded cases were SRY positive (i.e. representing 80–90% of all cases), and they showed translocated SRY gene on the Y chromosome. Moreover, fewer cases of male sex reversal (46, XX) were SRY negative.Case presentationHerby, we report a rare case of a 35-year-old infertile male patient who presented with azoospermia, hypergonadotropic hypogonadism, and abnormal classical (46, XX) karyotype, as well as negative FISH for SRY gene. He had a previous negative biopsy and was asking for redoing micro-TESE, whoever he was discouraged as chances to find sperm is eventually nil, and instead, he was prescribed testosterone replacement therapy to correct hypogonadism.ConclusionTherefore, any case of non-obstructive azoospermia should be offered genetic testing trying to exclude non-treatable cases and for genetic counseling.

Diseases of the endocrine system in children in Ukraine and the provision of specialized care to pediatric patients in 2020

The articles provide information and analysis of statistical indicators on the state of endocrinological care for children in 2020 in general in Ukraine and in some regions, their dynamics for 2014—2020. Providing data on staffing of the pediatric endocrinology service; the state of inpatient care for children with endocrine diseases; disability due to endocrine pathology, which has been carried out in recent years, is constantly growing, in particular diabetes, hypothyroidism and others; diseases and prevalence of malignant diseases of the endocrine glands in children. It is also possible to provide data from the register of children with active endocrine diseases, namely, diabetes mellitus, including its various forms, pathological short stature, the disorders of sex differentiation (DSD). The problematic issues of specialized care for children with diseases of the endocrine system are highlighted.It is estimated that according to the register of children with diabetes mellitus (DM) in 2020, 10,743 patients under the age of 18 were registered (14.26 per 10,000 children), including 10,598 children receiving insulin therapy (with DM Type 1, other types of diabetes requiring insulin treatment) (14.07), 51 — with DM type 2, 66 children with neonatal diabetes, of which 36 diagnoses are genetically confirmed, and MODY is genetically confirmed in 48 children. The prevalence of diabetes among children aged 0—18 years in 2020 increased compared to 2014 by 34.9 %.For patients with DSD conduct a detailed cytognetic examination in the leading genetic laboratories. Responding to the database of such children, to which 654 patients were includ, in particular with chromosomal DSD — 347 children (53.1 %, 303 patients with Turner syndrome); of 46, XY DSD — 102 patients (15.6 %); of 46, XX — 205 patients (31.3 %), as well as 185 children with DSD due to congenital adrenal hyperplasia.It is reported that in 2020, 1,630 children with short stature under the age of 18 who need treatment with growth hormone were registered in Ukraine, including 1,223 children with pituitary and pituitary-cerebral dwarfism, 255 children with Turner syndrome, 65 — with Russell—Silver syndrome, 43 — with Prader—Willi syndrome, 21 children with short stature, born small for their gestational age (SGA), as well as 22 children with dwarfism due to chronic renal failure. The number of such volumes increases by an average of 10 %. These children receive treatment with growth hormone drugs at the expense of the state budget.

Ovarian yolk sac tumor in a patient with sexual differentiation disorder: a case description.

Yolk sac tumor (YST), also called endodermal sinus tumor, is a rare malignant tumor accounting for less than 1% of all ovarian malignancies and is the second most common malignant ovarian germ cell tumor (MOGCT) (1,2). Disorder of sexual differentiation (DSD), once known as hermaphroditism, is also a rare cause of intersexuality disorders, where an individual has both male and female gonads (3,4). Due to the rarity of the condition, most articles about DSD are case reports and are limited in number (3,5). To the best of our knowledge, the YST of the ovary in adult DSD has rarely been reported in the literature. Here, we report a case of an adult DSD patient with an ovarian YST and their follow-ups after surgical treatment and chemotherapy.

Severe Hemophilia A in a Patient with Sexual Differentiation Disorder: A Case Report

Hemophilia A is an inherited X-linked disease where the VIII Factor (FVIII) production is altered, causing hemorrhagic diathesis. It can be classified into mild, moderate or severe, depending on the levels of circulating FVIII. It is suffered by males with an incidence of 1 in 5000 live births. Women are carriers, and they transmit the mutation in 90% of the cases, whereas 10% are de novo mutations. Females are usually asymptomatic, showing normal or intermediate FVIII factor, although it is estimated that 1 in 100.000 carriers will show severe bleeding manifestations due to FVIII severe deficit. For this to occur, some of the following physiopathologic mechanisms should be present: 1) heterozygous compound mutations affecting both alleles of the FVIII; 2) Homozygous mutations; 3) Extreme lionization of all the normal X chromosomes; 4) Numerical or structural alterations of the X chromosomes, as in Turner´s syndrome; 5) Genetical mutation in a patient with XY genotype and female phenotype.The objective of this report is to describe the case of a girl with severe Hempohilia A and XY cariotype.Case report:A 2-year-old female patient presented to consultation, with no remarkable previous perinatal history nor family history of hematologic diseases, referred due to spontaneous hematomas and bleeding events of difficult medical management with a 4 ISTH score. Coagulation studies were performed, showing a FVIII level of less than 1%, with the rest of the blood parameters being normal. Coagulation studies of the mother showed FVIII levels of 30%, Von Willebrand antigen of 59% and ristocetin cofactor of 43%. The genetic analysis of both the child and mother informed a type I inversion of the 22 intron. A karyotype analysis of the patient is done. She is phenotypically a female, but she has a 46XY genotype. At present she is being studied to rule out if the sexual differentiation disorder is due to the lack of SRY gen (Swyer´s syndrome) or to insensitivity to androgens (Morris´syndrome).From the moment of the diagnosis, the patient started prophylaxis with recombinant FVIII factor, not showing complications.DiscussionThe severe manifestations of the X linked diseases are infrequent in females. Approximately 30% of the carriers of hemophilia have an activity of the FVIII of less than 40%, with the consequent risk of bleeding. The most common cause for this is the selective inactivation of the normal X chromosome, that usually occurs in a balanced and randomized fashion. The diagnosis of hemophilia is made based on the FVIII activity dosage, and is confirmed with the molecular study of the mutations of the gene. In asymptomatic carriers, the status of homozygous or heterozygous mutation must be determined.Similarly, it is important to know what is the patient´s karyotype, because although its frequency is low, the disease can be the result of a sexual differentiation disorder, as it is the case presented here, or a chromosomopathy. In both cases is important to follow up the patient interdisciplinary with endocrinology, to treat the hormonal disorders related to each situation.ConclusionIt is of paramount importance to obtain a complete clinical and molecular diagnosis, to perform a correct treatment and follow up, and also offer an adequate genetic counseling. DisclosuresNo relevant conflicts of interest to declare.

Surgical outcomes and socio-demographic pattern of hypospadias patients treated in a tertiary care center in Kabul, Afghanistan

Hypospadias is a congenital anomaly of male external genitalia and is the second most common congenital anomaly of male newborns after cryptorchidism. Although its prevalence in Afghanistan is unknown, anecdotal evidence shows that hypospadias is an important clinical and psychosocial problem in Afghanistan. There is no data available regarding the socio-demographic pattern of the disease and age at the time of surgery in Afghanistan context. The aims of this study were to identify socio-demographic pattern of hypospadias among patients and to determine surgical outcomes of hypospadias patients operated in a tertiary care center in Kabul. A descriptive case series design and non-probability consecutive sampling were used. Study population was 86 patients undergone urethroplasty during January 2018 to September 2019. A structured questionnaire was used to assess the dependent and independent variables. Follow up notes of patients' medical record files were reviewed to assess post-operative condition of the patients along with presence of any post-operative complications. The mean age at the time of repair was 6.2 years. Family history was positive in 16.3% and consanguinity in almost 56% of the patients. The most common type of hypospadias was distal shaft type (30.2%), penile chordae was present in 25.6% and pinhole meatus in 32.6% of the cases. The most common associated anomaly was cryptorchidism (9.3%) followed by inguinal hernia (2.3%). Peno-scrotal transposition was the most common sexual differentiation disorder (11.6%), however majority didn't have any disorder of sexual differentiation (83.7%) The most common complication was urethral stricture and meatal stenosis (9.3% each) followed by urethra-cutaneous fistula (7%) in this study, although remarkable majority (74.4%) was complication free. Urethral advancement procedure was more practiced in distal type (94.7%) and 2-stage repair for the proximal type (70%) of hypospadias. Findings showed that the age at repair for hypospadias in our center is much higher than the recommended age. Different than the literature, the most common complication was meatal stenosis. Majority of patients were result of consanguineous marriages. Procedure choice was different according to the type of hypospadias and preference of the surgeon.

Recently defined epileptic encephalopathy related to WWOX gene mutation: six patients and new mutations

ABSTRACT Purpose: Pathogenic variants of the WWOX gene have been linked to sexual differentiation disorders, spinocerebellar ataxia, and epileptic encephalopathy (EE). We evaluated the clinical and molecular data from six newly diagnosed patients with WWOX-related EE. Methods: Clinical and molecular findings in six patients with EE were investigated, and biallelic pathogenic variants in the WWOX gene were identified. Clinical exome sequencing and Sanger sequencing were performed. Results: Three variations, as well as two novel mutations, in the WWOX gene were detected. Conclusion: Pathogenic WWOX mutations are associated with early-onset EE. Here, we report the case of six children with WWOX-related EE.

Sex Determination and Sex Differentiation

Sex determination is arguably the most defining moment of our lives, the point where we inherit X or Y chromosome from our father. This initiates a cascade of events that sets in a train of morphological changes, genetic regulations and molecular mechanisms. Following this, our fate is further sealed during sex differentiation and gonadal development owing to the action of sex-specific gonadal hormones. Therefore, the profoundly divergent journeys of male and female lives are decided just by the toss of a genetic coin. The existence of a third gender is also an undeniable aspect of our society. The understanding of the functioning and genetic regulation of the complex process of sexual determination and differentiation is pivotal in comprehension of the basis of human life. Any deviation from the usual mechanisms in the critical stages of development leads to disorders of sexual differentiation leading to sexual ambiguity among individuals. This review discusses the mechanisms that contribute to female and male sex determination and gonadal development, in an attempt to understand the basics of human sex.

Linear and Nonlinear Heart Rate Variability Analysis in Gonadal Dysgenesis (Swyer Syndrome): A Case Report

Swyer syndrome is one of the disorders of sexual differentiation. Previous studies have demonstrated increased sympathetic activity with heart rate variability (HRV) analysis with decreasing estradiol levels. One patient presented a pure 46, XY gonadal dysgenesis with female phenotype. Cardiac autonomic modulation was assessed through HRV analysis while at rest. This research analyzed linear and nonlinear indexes. HRV analysis showed reduced parasympathetic and global modulation with an apparent increase in sympathetic tone and a loss of HR fractal dynamics [...]

Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility.

To identify the contribution of mutations in the Desert Hedgehog (DHH) gene to the disorders of sexual differentiation (DSD) and male infertility. The study included a total 430 subjects, including 47 gonadal dysgenesis cases, 6 patients with undescended testis and infertility characterized by azoospermia, 125 infertile male patients characterized by oligoasthenozoospermia, 24 patients with oligoasthenoteratozoospermia, and 200 ethnically matched normozoospermic fertile men who had fathered a child in the last two years. Sequencing of the complete coding region of the DHH gene was undertaken to find its contribution to the DSD and male infertility. We observed four novel mutations in the DHH gene in the cases with different reproductive anomalies. A synonymous substitution, c. 543C>T (p.His181His) was observed in 6.6% oligoasthenozoospermic infertile males and 1.5% normozoospermic fertile control samples (RR = 4.4077, 95%CI 1.19-16.29). Another synonymous substitution, c.990G>A (p.Ala330Ala) was observed in an infertile patient with unilateral undescended testis (case #12). Insertion of G at c.1156insG (p.Arg385fs) was observed in a case with bilateral undescended testis and azoospermia (case #23). In gonadal dysgenesis category, two mutations, insertion of G at c.1156insG (p.Arg385fs) and c.997A>G (p.Thr333Ala) substitution were observed in one case (case #34). These mutations were completely absent in control samples. Mutations in the DHH gene impact reproduction with mild mutations affecting fertility, and severe or multiple mutations resulting in gonadal dysgenesis.

168 Non invasive prenatal testing and ultrasound fetal sex discrepancy: what are we missing?

Non invasive prenatal testing (NIPT) for fetal sex chromosomes has a sensitivity of 99%. However, discordant fetal sex results on NIPT and anatomical ultrasound (US) have been reported at a rate of 0.0-0.9%. These results are commonly attributed to sampling errors, a vanishing twin, placental mosaicism, or disorders of sexual differentiation. The aim of this study was to identify additional genetic causes of this discordance. This was a retrospective observational study from 8/2015 -1/2020. A database was queried to identify discordance between fetal sex reported on NIPT and the observed genital phenotype on US. Pregnancies with anomalies and ongoing multifetal gestations were excluded. The NIPT brand, fetal fraction, invasive testing results, and pregnancy outcomes were reviewed. Twenty seven cases of discordance were identified, representing 0.2% of patients. NIPT was normal in 24 cases, and 45X was predicted in 3. Cases were classified into 5 categories (Table 1). Invasive testing was performed in 13 cases, with abnormal genotypes identified in 7 cases, including abnormal karyotypes in all 3 cases with NIPT consistent with 45X and male genitalia (Table 2). In 5 cases, the patient chose pregnancy termination. In cases with normal NIPT and discordant genitalia, invasive testing identified abnormal genotypes in 4 cases, with karyotype consistent with US in the remaining 6 cases. In 14 cases without invasive testing, 7 had normal anatomy at birth, with genitalia consistent with US. Five of these cases were likely secondary to “vanishing twin” based on early US demonstrating an additional non-viable gestation. In 2 cases without invasive testing, ambiguous genitalia was noted at birth, with presumptive diagnoses of partial androgen insensitivity. In most pregnancies with normal NIPT results and phenotypically normal appearing but discordant genitalia, the genotype is consistent with phenotype. However, some have genetic abnormalities. All pregnancies with discordant NIPT/US results should be offered invasive testing to inform counseling and pregnancy management.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Role of Transperineal Ultrasound (TPUS) in Children with Ambiguous Genitalia.

Objectives Accurate delineation of anatomy in children with ambiguous genitalia early in life is important. This commonly involves conventional fluoroscopic genitogram (traumatic to the child) and magnetic resonance imaging (MRI) examination (involves sedation). In this study, our objectives were twofold: (1) to describe the findings on transperineal ultrasound (TPUS) in normal children and (2) to describe the findings on TPUS in children with ambiguous genitalia and correlate them with conventional genitogram. Materials and Methods TPUS was prospectively performed in 10 children without genital ambiguity (5 girls and 5 boys). Subsequently, 15 consecutive children having disorders of sex differentiation (DSDs) with genital ambiguity underwent TPUS. The presence or absence of müllerian structures was documented. Of these patients, 14 also underwent conventional genitogram as a part of routine evaluation. The gold standard was established either by comparison with surgical findings (in patients who underwent surgery) or by comparison with a combination of findings on genitogram and transabdominal ultrasound in patients who did not undergo surgery. Results In all normal children, lower urogenital tracts could be clearly delineated on TPUS. Out of the 15 children with ambiguous genitalia, TPUS could establish the presence/absence of müllerian structures in 14. This was concordant with findings on conventional genitogram/surgery. In one patient, müllerian structure was missed on TPUS but demonstrated on genitogram. In two children, TPUS showed the müllerian structure, which was not seen on genitogram. When both the controls and the cases were combined, TPUS had an accuracy of 95% and specificity of 100% in the detection of müllerian structures. Conclusion TPUS is feasible and accurate in demonstration of lower urogenital tract anatomy in children with DSDs having ambiguous genitalia. It can be performed without sedation, and is suitable for use as a screening modality in children with ambiguous genitalia.

Early diagnosis of CYP17A1 compound heterozygous mutations in a 46, XY child with disorders of sexual development

17-Hydroxylase/17,20-lyase deficiency is a rare congenital disorder accounting for 1% of congenital adrenal hyperplasia. This disease is recessively expressed as autosomal inheritance through mutations in the CYP17A1 gene, leading to defective levels of glucocorticoids and sex hormones. Individuals with loss-of-function mutations usually present with phenotypic female genitalia, primary amenorrhea, or hypertension in puberty caused by excessive production of mineralocorticoids. In this report, we describe a girl with CYP17A1 mutations diagnosed even though the pathognomonic symptoms had not developed. Herein, we report a case of a 3-year-old girl who prenatally diagnosed as a 46, XY female. After birth, the baby had normal female-type external genitalia without symptoms. She underwent a gonadectomy at the age of 3 years. To explore the pathogenesis of her condition, her genomic data were reviewed for genes involved in disorders of sexual differentiation (DSDs) using high-throughput sequence data from a whole-exome study. Pathogenic variants causing frameshift mutation involving codon 329 of CYP17A1 and a concomitant missense mutation involving codon 358 of the same gene were detected, mutations which are likely to result in loss of function of the enzyme. Each mutation was inherited from each of the parents, both holding carrier status. In addition, her younger sister (46, XX) acquired those identical variants without any abnormal phenotypical traits. Loss-of-function mutations of CYP17A1 which may cause secondary hypertension are not commonly identified in early life because of the wide spectrum of clinical manifestations and various pathophysiologies, which manifest in different sexes. Affected cases usually present later in life with hypertension or primary amenorrhea. High-throughput sequencing is suggested in DSD cases as it may give a precise diagnosis, enabling a proactive treatment plan and prevention of sequelae that potentially occur in puberty.

Congenital Adrenal Hyperplasia in Patients with Disorders of Sexual Differentiation

Congenital Adrenal Hyperplasia (CAH) is considered to be the most common cause of genital ambiguity in children. According to World’s literature, 90-95% of this disease is caused by 21-hydroxylase deficiency that impairs the synthesis of cortisol and aldosterone. The consequent excess in androgen production leads to virilization in the affected females. This study was aimed to find the number of cases with CAH (21-hydroxylase deficiency) in the children presented with disorders of sexual differentiation. For this purpose, 100 patients presented to The Children’s hospital for gender assessment were taken and their 17- OH progesterone levels were measured to confirm 21-hydroxylase deficiency, and chromosomal analysis was done to confirm chromosomal sex. Results indicated that out of 100 patients 49 were suffering from CAH. 63.2% of CAH patients were initially presented as males. Out of these, 44.8% were reassigned female gender on chromosomal analysis. So, it is concluded that the majority of patients presented with genital ambiguity in the tertiary care health facility have the ambiguity due to congenital adrenal hyperplasia.

Morocco's First Biobank: Establishment, Ethical Issues, Biomedical Research Opportunities, and Challenges.

Background Biobanks are highly organized infrastructures that allow the storage of human biological specimens associated with donors' personal and clinical data. These infrastructures play a key role in the development of translational medical research. In this context, we launched, in November 2015, the first biobank in Morocco (BRO Biobank) in order to promote biomedical research and provide opportunities to include Moroccan and North African ethnic groups in international biomedical studies. Here, we present the setup and the sample characteristics of BRO Biobank. Methods Patients were recruited at several departments of two major health-care centers in the city of Oujda. Healthy donors were enrolled during blood donation campaigns all over Eastern Morocco. From each participant, personal, clinical, and biomedical data were collected, and several biospecimens were stored. Standard operating procedures have been established in accordance with international guidelines on human biobanks. Results Between November 2015 and July 2020, 2446 participants were recruited into the BRO Biobank, of whom 2013 were healthy donors, and 433 were patients. For healthy donors, the median age was 35 years with a range between 18 and 65 years and the consanguinity rate was 28.96%. For patients, the median age was 11 years with a range between 1 day and 83 years. Among these patients, 55% had rare diseases (hemoglobinopathies, intellectual disabilities, disorders of sex differentiation, myopathies, etc.), 13% had lung cancer, 4% suffered from hematological neoplasms, 3% were from the kidney transplantation project, and 25% had unknown diagnoses. The BRO Biobank has collected 5092 biospecimens, including blood, white blood cells, plasma, serum, urine, frozen tissue, FFPE tissue, and nucleic acids. A sample quality control has been implemented and suggested that samples of the BRO Biobank are of high quality and therefore suitable for high-throughput nucleic acid analysis. Conclusions The BRO Biobank is the largest sample collection in Morocco, and it is ready to provide samples to national and international research projects. Therefore, the BRO Biobank is a valuable resource for advancing translational medical research.

Symptomatic prostatic utricle: various approaches for treatment

BackgroundPediatric presentations of a prostatic utricle have received only little attention. The incidence of symptomatic prostatic utricle has been reported but most cases are asymptomatic. The purpose of this study is to highlight the various clinical presentations and surgical approaches to treat a symptomatic prostatic utricle.ResultsThis study includes a series of 7 cases over a period of 5 years. The diagnosis of prostatic was made on the basis of clinical presentations, ultrasonography, micturating cystourethrogram, and cystoscopy.Of the 7 patients, the newborn patient had antenatally detected abdominal cystic mass which presented with postnatal urinary retention, 5 patients had various urinary complaints, and 1 older child with disorder of sexual differentiation (DSD) had urinary incontinence. Depending upon the grade of prostatic utricle, treatment was done in the form of laparoscopic-assisted excision in 1, laparotomy and excision in 1, perineal excision in 2, and cystoscopic fulguration in 3 patients. Postoperative period was uneventful. All the patients were followed for a period of 1–2 years. Most of them were asymptomatic except one child who had recurrent episodes of epidydimo orchitis which was treated conservatively, and he was also asymptomatic at the end of 1 year. Five patients who had associated hypospadias were observed for one year for any urinary complaints before they underwent definitive repair for hypospadias.ConclusionProstatic utricle is a vestigial remnant of müllerian duct most commonly associated with posterior hypospadias. High index of suspicion for prostatic utricle in cases with recurrent urinary complaints helps in timely detection and appropriate treatment can prevent further complications. Cystoscopy and micturating cytourethrogram remains the gold standard for diagnosis.

Disorders of sex differentiation: state of the problem 15 years after the Chicago consensus

It is well known that the nomenclature and classification were changed in 2005 at the international consensus conference on intersex disorders, held in Chicago, where, among others, the following recommendations were proposed: (1) all children should be assigned a gender identity, and this should be done as quickly as possible, taking into account the time required for the examination. (2) all infants with congenital adrenal hyperplasia and 46,XX karyotype, including those with pronounced masculinization, must be raised as women. (3) Surgical treatment should be performed early and in cases of feminizing genitoplasty, clitoral reduction should be performed simultaneously with reconstruction of the urogenital sinus (separation of the vagina and urethra). An analysis of contemporary literature shows that all these theories, proposed 15 years ago at the Chicago meeting, failed to stand the test of time. New nomenclature and classification are constantly being revised. Currently, many groups of patients want to abolish the term «sexual maturity disorders.» Recommendations regarding gender reassignment and appropriate early surgical treatment have been completely ignored in some countries. All this was largely facilitated by the confrontational activities of a number of support groups.

46, XX male syndrome- testicular disorder of sexual differentiation

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)