Vulva Research Articles

Identification of novel variants and candidate genes in women with 46,XX complete gonadal dysgenesis.

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. 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. 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. 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.

Bilateral Ectopic Ureters with Vaginal Insertion in a Duplex Collecting System: A Case Report of a Rare Case

Abstract The usual opening of the ureters is in the trigone of the bladder. However, it may open in an infrasphincteric location causing urinary incontinence with normal voiding. This is more commonly associated with a duplex collecting system in females, albeit, a bilateral occurrence of ectopic ureters with drainage into the vagina is rare. We report a rare case of bilateral occurrence of a duplex collecting system with drainage into the vagina. She was a 3-year-old girl with a complaint of continuous dripping of urine despite normal voiding. There was no history of fever, difficulty with micturition, fecal soiling, back swelling, or pelvic surgery in the past. She had normal female external genitalia with two openings in the vestibule. A computerized tomography urography showed a bilateral duplex collecting system with prompt and symmetric excretion of contrast, and dilated ureters of the upper renal moiety draining into the vagina bilaterally. We reimplanted the ectopic ureters with a resolution of urinary incontinence.

New species of Eupolyphaga Chopard, 1929 and Pseudoeupolyphaga Qiu & Che, 2024 (Blattodea, Corydioidea, Corydiinae), with notes on their female genitalia.

Two new species of Eupolyphaga (E.bicolor Han, Che & Wang, sp. nov. and E.nigra Han, Che & Wang, sp. nov.) and six new species of Pseudoeupolyphaga (P.flava Han, Che & Wang, sp. nov., P.deficiens Han, Che & Wang, sp. nov., P.magna Han, Che & Wang, sp. nov., P.longiseta Han, Che & Wang, sp. nov., P.latizona Han, Che & Wang, sp. nov., and P.baimaensis Han, Che & Wang, sp. nov.) are described and illustrated. The female external genitalia and spermathecae of these two genera are reported and the role of these characters in species delimitation is discussed.

Characterization of urethra closure in female neonatal mice at histological and molecular levels.

Female hypospadias is a little-known and poorly studied birth defect. This research establishes an anatomical and molecular foundation for future research to investigate the origins of this defect. Hypospadias is a congenital anomaly of the external genitalia where the urethra does not properly close. In humans, hypospadias is mostly reported in male newborns, whereas in females hypospadias is rare, although it is generally considered to be under-reported. Improper urethra closure in the female genitalia can cause recurrent genitourinary tract infections and infertility. In mice, female hypospadias was induced by exposure to exogenous estrogenic compounds. Aside from the link between estrogen exposure and female hypospadias, the process of female urethra closure is largely unstudied, with the precise timing of urethra closure and associated molecular mechanisms remaining poorly understood. To address this gap, we determined when urethra closure occurs and identified gene expression patterns during the process of urethra closure in female neonatal mice from postnatal day (PND) 5 to 10. Using whole mount imaging and histology, we discovered that the initiation of urethra closure begins at PND7, and urethra closure is fully completed by PND10. To identify the genes associated with urethra closure, we conducted bulk RNA sequencing on female external genitalia prior to and after urethra closure. Gene ontology analyses revealed an increase in steroidogenic gene expression (Star, Hsd3b6, and Cyp17a1) during urethra closure, suggesting that the female genitalia locally produce steroids which could facilitate steroid signaling within the genitalia. With this study, we establish an anatomical timeline of female urethra closure and hypothesize a paracrine steroid signaling mechanism of urethra closure. These observations provide entry points to aid in further understanding external genital abnormalities, like hypospadias, in females.

Mixed Gonadal Dysgenesis: A Narrative Literature Review and Clinical Primer for the Urologist.

Mixed gonadal dysgenesis is a difference of sex development that is often confused with other conditions. Individuals have a 45,X/46,XY karyotype. Gonads are characterized by a streak gonad and a dysgenetic testis at varying levels of descent. Persistent Müllerian structures are typical (eg, hemi-uterus). There is significant phenotypic heterogeneity of the internal and external genitalia that, together with different interpretations of the definition, have contributed to a poor understanding of the condition among pediatric urologists. Mixed gonadal dysgenesis is one manifestation of the 45,X/46,XY karyotype. 45,X/46,XY mosaicism can also be associated with typical female or male external genitalia. This review aims to clarify the mixed gonadal dysgenesis definition and to provide urologists with diagnostic and management considerations for affected individuals. We searched 3 medical databases for articles related to mixed gonadal dysgenesis. Two hundred eighty-seven full-text abstracts and manuscripts were reviewed for content pertinent to: (1) clarifying the definition of mixed gonadal dysgenesis, and (2) describing the following related to the care of affected individuals: prenatal and neonatal evaluation and management, genital surgery, gonadal malignancy risk and management, fertility, gender dysphoria/incongruence, puberty and long-term outcomes, systemic comorbidities, and transitional care. Fifty articles were included. Key points and implications for each of the above topics were summarized. Mixed gonadal dysgenesis exists on a wide phenotypic spectrum and management considerations reflect this heterogeneity. Care for individuals with mixed gonadal dysgenesis is complex, and decisions should be made in a multidisciplinary setting with psychological support.

(136) LABIA MINORA: A COMPREHENSIVE REVIEW

Abstract Introduction The labia minora (LM) is a part of the external female genitalia that varies greatly in form and appearance, and changes at each developmental stage of a woman. Its highly neurovascular nature and proximity to the clitoris allows it to play a vital role in sexual function. Along with the labia majora, it helps to protect the opening of the urethra and vagina. The perception of a normal LM is dependent on cultural and social context and influences the kinds of procedures that are done on the LM. Objective This study aims to comprehensively review labial anatomy, development, pathology, its role in sexual function, perceptions of labial appearance, and labial procedures. The goal is to understand the mechanism and purpose of the evolution of the LM and its effects on anatomical and sexual function. Methods We reviewed journal articles from 1988 to 2023 concerning labial anatomy, physiology, pathology, piercings, tattoos, and labial procedures such as labiaplasty, genital mutilation, episiotomies. We also reviewed cultural perceptions of its structure, its role in sexual function and its composition and function in the transgender population. Results The LM is highly neurovascular and engorges with blood with sexual stimulation. The structural changes are influenced by hormone levels. Perception of normal appearance varies by cultural and societal norms, influencing procedures performed in the area. Due to the histological composition of the LM, it has many manifestations of dermatological diseases. The LM is also susceptible to infectious, neoplastic, drug-induced, inflammatory, autoimmune and other systemic diseases. Limited information exists on LM piercing and tattoos. The size discrepancies of the LM may cause psychological distress, with conflicting research on its impact on sexual sensitivity or function. Labial procedures such as labiaplasty may enhance sexual satisfaction while female genital mutilation may reduce sexual satisfaction. There is a lack of comprehensive documentation of techniques of LM creation in transgender women and a lack of long-term follow-up studies post-vaginoplasty. The lymphatic structure within the LM is poorly understood, emphasizing the need for further research. Conclusions The labia minora is important for arousal and sexual function and its changes over time is dependent on hormone levels. The appearance and structure drive the kinds of labial procedures that are conducted and significantly affects sexual health. There is a need for further studies of the labia minora to understand its complexities and evolution. Disclosure No.

(005) MRI TECHNIQUES FOR IMAGING BIOMARKERS OF RADIATION-INDUCED DAMAGE TO FEMALE ERECTILE TISSUES AND OTHER GENITOPELVIC ORGANS

Abstract Introduction Difficulties with arousal and orgasm are common in female patients after pelvic radiation. Yet, current classifications of toxicity and normal tissues in radiation oncology account poorly for the anatomy and critical function of female erectile tissues (arousal and orgasm) with respect to patients’ capacities to continue to engage in pleasurable sexual behaviors after cancer treatment. MRI imaging biomarkers of dose-volume dependent radiation damage can provide objective measures of the impact of interventions, help predict sexual dysfunction, and allow for re-optimization of therapy for early mitigation of radiation damage to female erectile tissues. Objective The aim of this project is to develop and optimize MRI imaging techniques for female erectile tissues and other genitopelvic organs. Optimization of this MRI protocol will allow us to establish quantitative and qualitative indices of radiation damage to specific sexual organs, providing mechanistic insights into how to measure radiation damage of current and future therapies. Methods This prospective study includes two female-identifying volunteers with healthy female pelvic anatomy who underwent MRI scans using a 3.0T MRI (Prisma, Siemens Healthcare) scanner. The protocol (Table 1) included 2D T2-weighted turbo spin-echo (TSE) sequences in the axial (spatial resolution 0.5x0.5x2mm), coronal (spatial resolution 0.5x0.5x3mm), and sagittal planes (spatial resolution 0.3x0.3x2mm), T2-weighted with fat saturation in the axial plane (spatial resolution: 0.8x0.8x4mm) diffusion-weighted tensor imaging (DTI, axial plane with 30 diffusion directions and b-values 0s/mm2 and 400s/mm2, TR/TE: 3000/57ms, spatial resolution 1.3x1.3x5mm). Protocol optimization in healthy volunteers consisted of imaging without gadolinium contrast, while future imaging in patients will also include dynamic contrast-enhanced MRI (3D T1-weighted radial acquisition in the axial plane, with 4.7s temporal resolution, 20 slices, spatial resolution 0.8x0.8x2mm) and T1 mapping (axial plane variable flip angle, B1-corrected acquisition with 5 flip angles: 5, 10, 15, 20, 30 degrees, TR/TE: 5.9/2.4ms, with 0.8x0.8x2mm spatial resolution). The sexual regions of interest (ROIs) included the female external genitalia, vagina, bulboclitoris (clitoris and vestibular bulbs), pelvic neurovasculature, and pelvic floor muscles which were visualized and contoured per standard protocols. Results The axial T2-weighted TSE sequences in 2mm slices provided clear visualization of the female erectile tissues for contouring the bulboclitoris, vaginal canal, and external genitalia (Figure 1). The T2-weighted sequences with fat saturation allows us to conduct MR neurography to evaluate the three-dimensional visibility of the nerves (plexus, pudendal and cavernous), enabling us to localize and characterize nerve abnormalities with dose-dependent radiation damage (Figure 2). Perfusion time intensity curves created with the T1 DCE scans can assess changes in vasculature, and the initial areas under the time to signal intensity curve (IAUC) will act as biomarkers for erectile tissue perfusion and permeability. Additional biomarkers include ROI intensity and volume/thickness for both erectile tissues and the vagina wall, as well as fractional anisotropy for the vagina alone. Lastly, we explore the clinical applications of DTI with fiber tractography to evaluate pelvic floor musculature. Conclusions These MRI techniques will be the first to validate normal tissue toxicity imaging biomarkers for radiation damage, allowing us to objectively measure dose-dependent inflammatory, fibrotic and vasculogenic effects of radiotherapy. Disclosure No.

Understanding Professionals' Knowledge Regarding Factors Influencing Changes in Attitudes toward Female Genital Mutilation/Cutting in Post-Migration Communities in Geneva, Switzerland.

Female genital mutilation or cutting (FGM/C) is a practice involving the partial or complete removal of the external female genitalia for non-medical reasons. To facilitate attitude changes, the ecological model of behavior change considers multiple levels of influence and their relationships with environmental and behavioral factors. The combined effects of migration and cultural adaptation result in a transformative process that leads to decreased support for FGM/C. This qualitative study aimed to gain knowledge from FGM/C field professionals regarding the factors promoting behavioral changes in migrant communities in Geneva, Switzerland. Between September and October 2023, we conducted semi-structured interviews using a reflexive thematic analysis. Our qualitative research is reported in accordance with the COREQ criteria. A data analysis was performed using NVivo 14 software. Four influential dimensions were identified, each with associated factors. The first dimension, the social level, includes (1) the impact and implementation of anti-FGM/C laws. The second dimension, the community level, encompasses four factors such as (2) religion, (3) a multifaceted examination of social aspects, (4) navigating language barriers and raising awareness, and (5) cultural adaptation processes. The third dimension, the interpersonal level, includes factors such as (6) changing views on the marriage prerequisite. Finally, the fourth dimension, the personal level, is associated with (7) women's experiences and perspectives regarding FGM/C. The findings highlight seven environmental factors, both within and across dimensions of the ecological model, that interact with human behavior to enable an adaptive cultural process. This process influences changes in attitudes and behaviors regarding FGM/C.

"A part of my life". A qualitative study about perceptions of female genital mutilation and experiences of healthcare among affected women residing in Sweden.

Female genital mutilation (FGM) is defined as all procedures involving partial or total removal of the external female genitalia, or other injuries to them for non-medical reasons. Due to migration, healthcare providers in high-income countries need to better understand the consequences of FGM. The aim of this study was to elucidate women's experiences of FGM, with particular focus on perceived health consequences and experiences of healthcare received in Sweden. A qualitative study was performed through face-to-face, semi-structured interviews with eight women who had experienced FGM in childhood, prior to immigration to Sweden. The transcribed narratives were analyzed using content analysis. Three main categories were identified : "Living with FGM", "Living with lifelong health consequences" and "Encounters with healthcare providers". The participants highlighted the motives behind FGM and their mothers' ambivalence in the decision process. Although the majority of participants had undergone FGM type 3, the most severe type of FGM, the lifelong health consequences were diverse. Poor knowledge about FGM, insulting attitude, and lack of sensitive care were experienced when seeking healthcare in Sweden. Our findings indicate that FGM is a complex matter causing a diversity in perceived health consequences in women affected. Increased knowledge and awareness about FGM among healthcare providers in Sweden is of utmost importance. Further, this subject needs to be addressed in the healthcare encounter in a professional way.

Cosmetic Gynecology

Cosmetic Gynecology (CG) is a rapidly emerging subspecialty. With the large media coverage, it had gained popularity in last few years. This review aims to provide an overview of the advancements, techniques, and considerations in aesthetic gynecology. We discuss common procedures such as labiaplasty, vaginal rejuvenation, and clitoral hood reduction, highlighting their indications, surgical techniques, outcomes, and patient satisfaction. Additionally, we explore emerging trends such as non-surgical treatments using laser therapy and Platelet-Rich Plasma (PRP) for tissue rejuvenation. Ethical considerations, patient education, and the importance of a multidisciplinary approach are also discussed. GC addresses both functional as well as aesthetic aspect of female external genitalia and is being considered as an excellent opportunity to address psychosexual issues if present. Overall, aesthetic gynecology offers valuable options to improve women’s confidence, comfort, and quality of life.

Phenotypic variability and management of patients with mosaic monosomy X and Y chromosome material: a case series

Backgroundwe aim to discuss the origin and the differences of the phenotypic features and the management care of rare form of disorder of sex development due to Mosaic monosomy X and Y chromosome materiel.MethodsWe report our experience with patients harboring mosaic monosomy X and Y chromosome material diagnosed by blood cells karyotypes and cared for in our department from 2005 to 2022.ResultsWe have included five infants in our study. The current average age was 8 years. In four cases, the diagnosis was still after born and it was at the age of 15 years in one case. Physical examination revealed a variable degree of virilization, ranging from a normal male phallus with unilateral ectopic gonad to ambiguous with a genital tubercle and bilateral not palpable gonads in four cases and normal female external genitalia in patient 5. Karyotype found 45, X/46, XY mosaicism in patient 1 and 2 and 45, X/46, X, der (Y) mosaicism in patient 3, 4 and 5. Three cases were assigned to male gender and two cases were assigned to female. After radiologic and histologic exploration, four patients had been explored by laparoscopy to perform gonadectomy in two cases and Mullerian derivative resection in the other. Urethroplasty was done in two cases of posterior hypospadias. Gender identity was concordant with the sex of assignment at birth in only 3 cases.ConclusionBecause of the phenotypic heterogeneity of this sexual disorders and the variability of its management care, then the decision should rely on a multidisciplinary team approach.

INTERROGATING THE PERSISTENCE OF FEMALE GENITAL MUTILATION IN ILORIN, KWARA STATE, 2000-2020

Female genital mutilation is also known as female genital cutting and female circumcision which comprises all procedures involving a partial or total removal of the external female genitalia either for cultural or other non-therapeutic reasons. FGM is a sensitive topic and issue because it cuts across several cultures and needs to be addressed with great care, without affecting people’s feelings as it touches on other people’s cultures. The practice is, therefore, still deeply entrenched in the Nigerian society. Despite efforts to raise awareness of FGM’s medical complications through governmental and non-governmental organizations, the practice persists in some communities, and this makes one ponder on the factors that seem to preserve the practice. This paper using both primary and secondary sources of historical research methodology assesses the socio-cultural and religious factors that contributed to the continuous practice of female genital mutilation in Ilorin despite the international condemnation. In Nigeria, the South-south (77 percent) has the highest incidence of Female Genital Mutilation among adult women, followed by the South-east (68 percent), and the South-west (65 percent). However, it was only lightly practised in the North, surprisingly leaning toward a more extreme form. At the national level, 41 percent of adult women have had Female Genital Mutilation typically carried out by a traditional circumciser using a blade. There was a significant relationship between the persistence of the practice of FGM and social structures, cultural, and religious beliefs. The study shows that the continuous practice of female genital mutilation in Ilorin is not due to ignorance, but a longstanding tradition and religious belief.

Review of the genus Carriola Swinhoe, 1922 (Lepidoptera, Erebidae, Lymantriinae), with descriptions of four new species

The genus Carriola Swinhoe, 1922, which is considered a recent synonym of Arctornis Germar, 1810, is revised on the basis of the wing pattern, the absence of abdominal tymbal organs and the genitalia of both sexes. Diagnostic and faunistic data are provided for the five known species previously classified as Carriola. In addition, four new species are described: C. wittisp. nov. from Borneo, C. polyakovisp. nov., C. shorokhovisp. nov., and C. zolotuhinisp. nov. from the Philippines. Comparative diagnoses, illustrations of external characters, including male and female genitalia, and information on distribution are provided for all species.

A theoretical model of cross-flow heat transfer for the cooling process in a horizontal moving bed of high-temperature particles

ABSTRACT Besides waste gas and liquid, high-temperature particles are important media of waste heat and their temperature exceeds 1000°C on many occasions. The cross-flow heat transfer is important in this waste heat recovering process, but there are few references reported about the theoretical modeling. Therefore, a theoretical model was developed for the cooling process in a horizontal moving bed of high-temperature particles. The purpose of the study is to estimate the influence of temperature field and flow field on heat transfer and bed resistance in the cross-flow cooling process. Three modes such as conduction, convection and radiation are considered in the model. This model was used to analyze heat transfer in a horizontal moving bed of cement clinker and was verified by comparing some simulative results with the tested and collected data from an actual cement clinker plant in China. The simulative temperature of cement clinker was 200°C as same as that collected in the actual cement clinker plant. In the moving bed, the highest pressure drop occurs at the front top and the strongest heat transfer occurs at the front bottom. In the considered conditions with even distribution of cooling air, the highest pressure drop is 3205.9 Pa/m, the biggest specific heat transfer rate of 1683.1 kW/m3. Thermal radiation plays a minor role in this cooling process with the biggest radiation proportion is only 0.149 at the front top. This mode plays a minor role in this cooling process of the cement clinker, comparing with the thermal convection. With constant flow rate of cooling air, the distribution can regulate the local cooling rate rather than the final temperature of the cement clinker.

A rare case report of ambiguous genitalia

An ambiguous genitalia is a commonly referred clinical scenario to endocrinology outpatient department. Accurate diagnosis is paramount to prevent associated salt-wasting crisis, direct the gender of rearing in the short-term, and monitoring for the development of malignancy in the gonads in the long-term. 17 beta-hydroxysteroid dehydrogenase 3 deficiency (17 β HSD 3) is one of the causes of defective testosterone biosynthesis. 17β-HSD3 deficiency should be suspected in children with female external genitalia with inguinal hernias or mild clitoromegaly; as well as males with ambiguous genitalia who develop virilization and gynecomastia at puberty. A hormonal evaluation may not always be diagnostic which makes genetic confirmation essential.

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

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

The unbroken chain of female genital mutilation: a qualitative assessment of high school girls’ perspectives

BackgroundFemale Genital Mutilation (FGM) is defined as any procedure that involves damage to the female external genitalia. This practice is majorly prevalent in Sudan, as it is estimated that over 12 million Sudanese women are circumcised. This study uncovers rural females’ knowledge and insights about FGM domestically.MethodsA qualitative, deductive study with thematic analysis was conducted. A total of 42 female high school students were recruited and divided into five focus groups, each of which included girls from four different high school classes in the main school of the study area. A topic guide was prepared and used to lead the focus groups. Thematic analysis was used, and the study data had been categorized into four themes: knowledge, procedure and performance, experience, and practice. The condensed meaning units of each theme were identified, then classified to formulate sub-themes.ResultsAll the participants indicated that FGM is a traditional practice in the village. The vast majority have heard about it from family members, mainly mothers and grandmothers. Regarding the procedure, all the participants agreed that midwives perform FGM, but most of them don’t know what exactly is being removed. According to all participants, mothers and grandmothers are the decision-makers for FGM. The majority of the participants stated that they do not discriminate between the circumcised and uncircumcised women and most of them agreed that circumcision has negative side effects. They have mentioned pain, difficult urination, and walking as early side effects, while psychological impacts and labor obstruction as late ones. Generally, the majority of the participants agreed that circumcision is not beneficial and should stop.ConclusionKnowledge regarding the dangers of FGM among high school girls is better than expected given the high prevalence of the practice. Generally, the process is well understood, the performers are known, the experience is universal, and the side effects are acknowledged. Nevertheless, a majority still showed an intent to circumcise their daughters in the future.

46,XX males with congenital adrenal hyperplasia: a clinical and biochemical description.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males. This study aims to describe the clinical and biochemical characteristics of a unique cohort of untreated male-reared 46,XX classic CAH patients from Indonesia and discusses treatment challenges. Nine untreated classic CAH patients with 46,XX genotype and 21OHD (n=6) or 11OHD (n=3), aged 3-46 years old, were included. Biometrical parameters, clinical characteristics, and biochemical measurements including glucocorticoids, renin, androgens, and the pituitary-gonadal axis were evaluated. All patients had low early morning serum cortisol concentrations (median 89 nmol/L) without significant increase after ACTH stimulation. Three patients with salt wasting 21OHD reported one or more periods with seizures and/or vomiting in their past until the age of 6, but not thereafter. The remaining patients reported no severe illness or hospitalization episodes, despite their decreased capacity to produce cortisol. In the 21OHD patients, plasma renin levels were elevated compared to the reference range, and in 11OHD patients renin levels were in the low-normal range. All adult patients had serum testosterone concentrations within the normal male reference range. In 21OHD patients, serum 11-oxygenated androgens comprised 41-60% of the total serum androgen concentrations. Glucocorticoid treatment was offered to all patients, but they refused after counseling as this would reduce their endogenous androgen production and they did not report complaints of their low cortisol levels. We describe a unique cohort of untreated classic 46,XX male CAH patients without overt clinical signs of cortisol deficiency despite their cortisol underproduction and incapacity to increase cortisol levels after ACTH stimulation. The described adolescent and adult patients produce androgen levels within or above the normal male reference range. Glucocorticoid treatment will lower these adrenal androgen concentrations. Therefore, in 46,XX CAH patients reared as males an individual treatment approach with careful counseling and clear instructions is needed.

NR5A1-related 46,XY partial gonadal dysgenesis: A case report and literature review

Rationale: Disorders/differences of sex development (DSD) include a diverse group of congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is discordant. It involves several variant genes, and one of them is NR5A1. NR5A1 encodes a signal transduction regulator in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal pathway, and pathogenic mutation in this gene is a cause of 46,XY DSD. Patient concerns: A 12-year-old individual raised as a girl was admitted to the hospital due to hirsutism and a deep voice that began at 11 years old. The individual exhibited testicular hypoplasia, clitoral hypertrophy, and female external genitalia. Diagnoses: The patient was diagnosed 46,XY partial gonadal dysgenesis. The cytogenetics revealed a 46,XY karyotype and DNA sequencing shown a variant in NR5A1. Pelvic magnetic resonance imaging showed absence of uterus and ovaries. The abdominopelvic ultrasound revealed bilateral testicle in bilateral groin. Pathology confirmed testes dysgenesis. Interventions: The patient underwent bilateral orchiectomy at age 12 years and was given a feminizing hormonal treatment of 0.5 mg/day of estradiol valerate tablets. Outcomes: The patient recovered well after surgery and hormonal treatment and had a regression in hirsutism and clitoromegaly. Lessons: 46,XY DSD is a rare disease that the development of chromosomal, gonadal, or anatomical sex is discordant, when diagnosed 46,XY DSD, the identification of an NR5A1 variant should be considered.

In Silico Analysis of Functional SNPs in Genes of Complete Androgen Insensitivity Syndrome (CAIS): A Retrospective, Case-Control Study.

Complete androgen insensitivity syndrome (CAIS) is one of the categories of androgen insensitivity syndrome (AIS) described as complete failure of the cell to react to androgens with external genitalia of a normal female. People with AIS condition are genetically male, with XY karyotype in each cell, but their bodies are unable to respond to male sex hormones (called androgens). It is associated with infertility as well as developing cancerous conditions. The genetic association of CAIS involves polymorphism of genes such as NR5A1, SOX9, SRD5A2, CBX2, GATA4, and SRY. Their mutation and participation in genetics of CAIS can be studied by Single Nucleotide polymorphism (SNP) analysis which is a way to detect genetic variations. SNP in coding region leads to synonymous and non-synonymous mutations. Hence, this study highlights analysis of SNPs associated with CAIS. Our aim is to study SNP analysis of NR5A1, SOX9, SRD5A2, CBX2, GATA4, SRY genes in Complete Androgen Insensitivity Syndrome. SIFT and Polyphen analysis was performed for all the genes and samples were subjected for PCR-SSCP technique. SNPs were analyzed for the genes associated with CAIS. Benign and damaging SNPs were identified. DNA Samples were amplified using PCR technique and they will be analyzed using Single-strand conformation polymorphism (SSCP). As SNPs have decreased stability, damaging and benign character, they can be used as candidate hallmarks in study of Complete Androgen Insensitivity Syndrome.