Disorders of Sex Development: Experience at a Tertiary Care Hospital in Bangladesh.

In newborns, it is an emergency to decide the appropriate sex for rearing and eventual prevention associated metabolic disturbances. The birth of a baby with ambiguous genitalia inevitably precipitates a crisis for the baby and its family. This retrospective analysis of hospital data was designed to determine the chromosomal and etiological diagnosis of children presented with suspected disorders of sex development (DSD) according to the newer DSD consensus document. We retrospectively analyzed the available medical records of all patients admitted into the inpatient departments of Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh from January 2014 to December 2019, and all patients with the diagnosis of DSD in the hospital record were initially selected for the study. A total of 60 admitted cases with a disorder of sex development were classified according to the new DSD classification. 46XX DSD were 63.3% (n=38), 46XY DSD were 33.3% (n=20), sex chromosome DSD were 3.3% (n=2). Among 38 cases of 46XX DSD, the most common cause was congenital adrenal hyperplasia (97.0%, n=37), one was 46XX testicular DSD. However, among 46XY DSD cases, partial androgen insensitivity/5α-reductase deficiency (50.0%, n=10) was most common disorder. Other causes of 46XY DSD included congenital adrenal hyperplasia (20.0%, n=4), testosterone synthesis defect (20.0%, n=4), testicular regression syndrome (n=1) and persistent Mullerian duct syndrome (n=1). Sex chromosome disorders are mixed gonadal dysgenesis (n=1), chimeric ovotesticular DSD (n=1). In this study, 46XX DSD was the commonest of all, showing the predominance of congenital adrenal hyperplasia, especially salt-losing type. Early detection and prompt treatment may help reduce mortality and morbidity from these acute life-threatening conditions.

A prospective study on disorders of sex development in Duhok city, Kurdistan region, Iraq: Genetic, etiology and clinical presentation.

Disorders of Sexual Development (DSD) encompass all types of intersex cases and have been reported globally. However, in Iraq, studies related to DSD are scanty.  The current single-center prospective study was carried out to find out the frequency, genetic and clinical presentation of different types of DSDs in the sample population of Duhok, Iraq. The sample comprises 40 DSD patients who have been referred to Hivi Pediatric Teaching Hospital in Duhok, Kurdistan region, Iraq, from June 2017 to June 2022. We conducted karyotype-based classification, laparoscopic-based internal organ diagnosis and abdominal ultrasound to diagnose DSDs in the target population. Of the total 40 cases, 19 (47.5%) were males, and 21 (52.5%) were females. Among them, 85 % were diagnosed as peno- scrotal hypospadias, 10% had clitoromegaly and the remaining were diagnosed as under-developed female-like genitalia. The majority of the patients were diagnosed with congenital adrenal hyperplasia (CAH) (55%), 37.5% were Testicular Feminization Syndrome (TFS) and the remaining were rare categories that we did not reach final diagnosis. Laparoscopy was done for 77.5 % of the participants of whom 30% had small uterus and ovaries, 25% had Intra-abdominal testes and the remaining had testes &ovaries, Mullerian Inhibitory Factor (MIF) deficiency and TFS. The study found different types of DSDs in the target population that requires both physical and psychological intervention. Future studies should focus on evaluating DSDs in larger populations and at multi-centers to understand the condition's trajectory in the Iraqi population.

Disorders of sex development: Challenges in a low-resource country.

AIM: We aimed to identify the challenges in the management of sexual development abnormalities in a low-resource country. METHODS: The study was retrospective from January 2000 to December 2017 based on patient records from two pediatric surgery departments. Epidemiological, clinical, paraclinical, treatment, and outcome data were studied. RESULTS: We collected data on 13 patients (average age = 7.95 years). The sex of rearing was as follows: three females (23%), 10 males (77%). Atypical genitalia other than hypospadias represented the reason for consultation in 92% of the cases. We could not find complete hormonal analyses; testosterone levels were studied in 69.23% of cases. We found the following disorders of sexual development (DSD): four patients with 46,XX karyotype (30.77%), eight patients with 46,XY karyotype (61.53%), and one patient with 46,XX/XY karyotype. Four patients had medical treatment only, four had surgical treatment only, and one patient had medical and surgical treatment. The medical treatment comprised topical administration of androgen. The surgical treatment consisted of feminizing genitoplasty for one patient and masculinizing genital surgeries for two patients. Six of the 13 patients were lost to follow-up. CONCLUSION: The socioeconomic difficulties of the population and the lack of access to basic diagnostic and paraclinical methods, coupled with the negative cultural representations of the pathology, constitute the challenges in the management of DSD in our practice.

Condition openness is associated with better mental health in individuals with an intersex/differences of sex development condition: structural equation modeling of European multicenter data.

BACKGROUND: Openness on one's health condition or (stigmatized) identity generally improves mental health. Intersex or differences of sex development (DSD) conditions have long been kept concealed and high levels of (internalizing) mental health problems are reported. This study examines the effects of condition openness on anxiety and depression and the role of mediating concepts in this population. METHODS: Cross-sectional data of individuals of 16 years and older with an intersex/DSD condition was collected in 14 specialized European clinics as part of the dsd-LIFE study. Patient-reported measures were taken on openness and shame (Coping with DSD), self-esteem (Rosenberg Self-Esteem Scale), satisfaction with care (CSQ4), anxiety and depression (HADS). Scores were compared per clinical group and data were analyzed via structural equation modeling (SEM) to calculate prediction and mediation models. RESULTS: Data of 903 individuals were included in this study (Turner syndrome (n = 284), 46, XY DSD (n = 233), CAH (n = 206) and Klinefelter syndrome (n = 180)). Participants were moderately open on their condition. High levels of both anxiety and depression were observed across the sample. In SEM analysis, the tested models predicted 25% of openness, 31% of anxiety and 48% of depression. More condition openness directly predicted lower anxiety and depression symptoms, as well as indirectly through increased self-esteem, self-satisfaction and satisfaction with social support. CONCLUSIONS: Condition openness is associated with lower anxiety and depression in individuals with an intersex/DSD condition. Healthcare may provide the necessary knowledge and skills to employ one's optimal level of self-disclosure in order to improve mental health.

First Adolescent Romantic and Sexual Experiences in Individuals With Differences of Sex Development/Intersex Conditions.

PURPOSE: Adolescence is an important period for sexual development, including sexual debut. The purpose of this study was to assess first romantic and sexual experiences and debut age in individuals with differences of sex development (DSD/intersex) and compare these with age-matched and gender-matched population control values. METHODS: Questionnaire data on sociodemographic characteristics, romantic and sexual milestones (e.g., masturbation, dating), satisfaction with sexual life and sexual activity at follow-up, self-esteem, and feelings of femininity or masculinity were collected from 976 participants in Europe with a DSD condition. Participants were divided into six diagnostic subgroups based on their diagnostic classification: women with Turner syndrome, congenital adrenal hyperplasia, 46XY-DSD nonvirilized, and 46XY-DSD female partially virilized conditions and men with 46XY-DSD male or Klinefelter syndrome. Age-specific and gender-specific reference values were retrieved from a Dutch population sample. RESULTS: Individuals with DSD were less likely to reach each of the romantic and sexual milestones compared to their peers without these conditions and they were significantly older when reaching these milestones. Between clinical subgroups, individuals with Klinefelter were significantly older when reaching milestones and in the female groups and individuals with Turner were the least likely to reach milestones. Furthermore, a higher age when reaching several romantic and sexual milestones was correlated with lower self-esteem, lower satisfaction with sexual life, and lower sexual frequency at follow-up. DISCUSSION: Due to a difference in biopsychosocial context, individuals with DSD often experience a different and/or delayed sexual development during adolescence. Healthcare providers should be aware of these differences in adolescents with DSD and their sexual development to optimize affirmative counseling.

Mental health status of children with disorders of sexual development and their correlates.

Disorders of sexual development (DSD) refer to the congenital abnormalities of chromosomes, gonads, or gender anatomy. Children with DSD usually experience more stress. The present study aims to evaluate the mental health status of children with DSD, and to explore the potential relevant factors. We included 30 children with DSD and 30 age- and gender-matched children without DSD as the control group. All the children and their parents completed the scales of the Hamilton Anxiety Scale (HAMA). Children over 8 years old (n = 22) completed the Screen Scale for Child Anxiety Related Emotional Disorders (SCARED), the Depression Self-rating Scale for Children (DSRSC), and the Egna Minnen av Barndoms Uppfostran-own memories of parental rearing practices in childhood. DSD children had significantly higher somatic anxiety, mental anxiety, and total anxiety scores than the control group (p < 0.001). The scores of the SCARED, anxiety, and depression subscales of DSD children were higher than those of control children (p < 0.05 and p < 0.001, respectively). The correlation analysis showed that the score of generalized anxiety was positively related to age and entertainment. The regression analysis showed that age was a major factor that affected generalized anxiety in DSD children, and neuroticism was a major factor of anxiety disorder and separation anxiety in DSD children. Children with DSD have obvious anxiety problems, which are associated with family environmental factors (entertainment, success, and conflicts) and age. It is important to focus emphasis on emotional stability in children with DSD for detecting anxiety-related emotional disorders early.

Disorders of Sex Development in a Large Ukrainian Cohort: Clinical Diversity and Genetic Findings.

Background: The clinical profile and genetics of individuals with Disorders/Differences of Sex Development (DSD) has not been reported in Ukraine. Materials and Methods: We established the Ukrainian DSD Register and identified 682 DSD patients. This cohort includes, 357 patients (52.3% [303 patients with Turner syndrome)] with sex chromosome DSD, 119 (17.5%) with 46,XY DSD and 206 (30.2%) with 46,XX DSD. Patients with sex chromosome DSD and congenital adrenal hyperplasia (CAH, n=185) were excluded from further studies. Fluorescence in situ hybridization (FISH) was performed for eight 46,XX boys. 79 patients underwent Whole Exome Sequencing (WES). Results: The majority of patients with 46,XY and 46,XX DSD (n=140), were raised as female (56.3% and 61.9% respectively). WES (n=79) identified pathogenic (P) or likely pathogenic (LP) variants in 43% of the cohort. P/LP variants were identified in the androgen receptor (AR) and NR5A1 genes (20.2%). Variants in other DSD genes including AMHR2, HSD17B3, MYRF, ANOS1, FGFR11, WT1, DHX37, SRD5A1, GATA4, TBCE, CACNA1A and GLI2 were identified in 22.8% of cases. 83.3% of all P/LP variants are novel. 35.3% of patients with a genetic diagnosis had an atypical clinical presentation. A known pathogenic variant in WDR11, which was reported to cause congenital hypogonadotropic hypogonadism (CHH), was identified in individuals with primary hypogonadism. Conclusions: WES is a powerful tool to identify novel causal variants in patients with DSD, including a significant minority that have an atypical clinical presentation. Our data suggest that heterozygous variants in the WDR11 gene are unlikely to cause of CHH.

Differences or Disorders of sex development in Boys: impact on fertility.

Differences or disorders of sex development (DSD) include various congenital conditions in which chromosomal, gonadal, or anatomical sex development is atypical. The incidence varies according to the category of DSD but the total incidence is high if hypospadias and undescended testes are included. Fertility prospects may be a concern for DSD patients and their parents. With the development of modern medical technologies and treatment opportunities, fertility diagnostics, information, and treatment have changed. Assisted reproductive technology has developed during the past decades and has become more available with an improving success rate. Intracytoplasmic sperm injection and testicular sperm retrieval, have further improved the possibilities for men with DSD to become biological parents. Some studies have determined the presence of germ cells in the gonads of patients with DSD suggesting that the potential for fertility may be higher than previously thought. However, fertility outcomes among individuals with DSD have not been fully investigated. Moreover, previous study showed that information on fertility problems and treatment possibilities given to patients with DSD needs to be improved. The use of registries to study fertility outcomes is essential for a better knowledge of fertility in patients with these rare conditions.

A Nationwide Study of the Prevalence and Initial Management of Atypical Genitalia in the Newborn in Scotland.

Provision of optimum healthcare for infants with atypical genitalia requires a clear understanding of the occurrence of this condition. The objective of this study was to determine the prevalence of atypical genitalia and its initial management. A prospective, electronic survey of clinicians within managed clinical networks in Scotland was undertaken between 2013 and 2019. Notification from clinicians was sought for term neonates requiring specialist input for atypical genitalia. Additional information was also sought from the 4 regional genetics laboratories that provided details for neonates who had an urgent karyotype performed for atypical genitalia or sex determination. In total, the study identified 171 term infants who required some investigation for atypical genitalia in the neonatal period, providing a birth prevalence of 1:1,881 term births. Of the 171 infants, 97 (57%) had specialist input over the first 3 months of life, providing a birth prevalence of 1:3,318 term births that received specialist input for atypical genitalia. A total of 92 of these 97 cases had complete 3-month follow-up data, 62 (67%) presented within 24 h of birth, and age at presentation ranged from birth to 28 days. Age at sex assignment ranged from birth to 14 days, and in 63 cases (68%), sex assignment occurred at birth. Thus, the birth prevalence of a case of atypical genitalia where sex assignment was reported to be delayed beyond birth was estimated at 1:11,097 births. In 1 case sex was re-assigned at 3 months. Atypical genitalia requiring specialist input within the first month of life are rare in term newborns, and in only a third of these cases, sex assignment is delayed beyond birth. This study provides new clinical benchmarks for comparing and improving the delivery of care in centres that manage these conditions.

Categorization of differences of sex development among Egyptian children and the role of antimullerian hormone and inhibin B.

Background: Differences of sex development (DSD) are congenital conditions linked to atypical development of chromosomal, gonadal, or anatomical sex. Objective: The aim of this study was to demonstrate our experiences at the Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU), Faculty of Medicine, Cairo University in the field of DSD by focusing on the clinical presentation, laboratory profile, classification, and etiological diagnosis of these conditions. In addition, the present study intended to delineate the importance of serum anti-Müllerian hormone (AMH) and inhibin B in detecting the presence of functioning testicular tissue. Methods: This cohort study included 451 infants and children with various clinical presentations of DSD. The study performed a retrospective analysis on medical records of established DSD cases to evaluate the clinical importance of AMH and inhibin B. In addition, newly diagnosed patients were prospectively analyzed. Results: Three hundred thirty-six (74.5%) patients were 46,XY DSD, 98 (21.7%) were 46,XX DSD, 14 patients had other karyotypes and 3 had missing karyotypes. Among the 46XY DSD patients, the most common cause was partial androgen insensitivity. In contrast, congenital adrenal hyperplasia constituted the most common diagnosis in 46,XX DSD cases. The cut off value of serum AMH was 14.5 ng/ml with 100% sensitivity and 55.1% specificity. Conclusion: Partial androgen insensitivity was the most important cause of 46,XY DSD in Egyptian children, and congenital adrenal hyperplasia was the most common cause of 46,XX DSD. AMH was valuable in detecting functioning testicular tissue.

The introduction of clinical genetic testing in Ethiopia: Experiences and lessons learned.

Limited data are available on genetic testing laboratories in low- and middle-income countries including those in sub-Saharan Africa (SSA). To characterize the need for genetic testing in SSA we describe the experience of MRC-ET Advanced Laboratory, a genetic testing laboratory in Ethiopia. Test results were analyzed based on indication(s) for testing, referral category, and diagnostic yield. A total of 1311 tests were run using the full MRC-Holland catalogue of Multiplex-Ligation Probe Amplification assays. Of all samples, 77% were postnatal samples, 15% products of conception (POC), and 8% amniotic samples. Of postnatal samples, the most common testing categories were multiple congenital anomalies (32%), disorders of sex development (17%), and Obstetrics/Gynecology (16%). Forty-three percent of postnatal samples were diagnostic, 11% were variants of uncertain significance (VUS), and 46% were normal with Trisomy 21 the most common diagnosis. Of POC samples, 10% were diagnostic, 34% revealed VUSs, and 55% were normal with Trisomy 18 the most common diagnosis. Of amniotic samples 17.5% were diagnostic, 3% revealed VUSs, and 79% were normal with Trisomy 18 the most common diagnosis. There is increasing demand for genetic testing in Ethiopia. Diagnostic genetic testing in SSA deserves increased attention as testing platforms become more affordable.

Gonadectomy in conditions affecting sex development: a registry-based cohort study.

OBJECTIVES: To determine trends in clinical practice for individuals with DSD requiring gonadectomy. DESIGN: Retrospective cohort study. METHODS: Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019. RESULTS: Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries. CONCLUSIONS: The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.

Molecular genetics of disorders of sex development in a highly consanguineous population.

Consanguinity increases the risk of hereditary diseases including disorders of sex development (DSD). There are minimal data on DSD in the highly consanguineous population of Saudi Arabia. This study reports the molecular genetics of a series of patients with different types of DSD. METHODS: We enrolled 77 patients from 47 families with DSD. DNA was isolated from peripheral leucocytes. Genes of interest were amplified by polymerase chain reaction and subsequently sequenced. RESULTS: Overall, 77 patients from 47 families (44 of them are consanguineous) had a total of 29 mutations; 16 of them were described before and 13 were novel mutations. The most common condition was 5-α reductase (SRD5A2) deficiency (25 patients from 18 families) and the most common mutation was a splice site mutation in intron 1 (c.282-2A>G). The next most common condition was 11-ß hydroxylase (CYP11B1) deficiency where 19 patients from 10 families had 8 mutations (7 of them are novel). Other mutations affected CYP17A1 with 2 novel and 2 known mutations in 7 patients; HSD3B2 with 2 known mutations in 11 patients of 4 families; StAR with 1 novel and 1 known mutations in 4 patients; NR0B1 with 1 novel mutation in 2 siblings; HSD17B3 with 1 known mutation in 3 siblings; LHCGR with 1 novel mutation in 2 siblings; and AR with 1 novel and 3 known mutations in 4 unrelated patients. CONCLUSION: In the highly consanguineous and homogeneous population of Saudi Arabia, SRD5A2 and CYP11B1 deficiencies are common causes of DSDs. Other DSDs occur less frequently but often with novel mutations.

Gender identity disorder (GID) in adolescents and adults with differences of sex development (DSD): A systematic review and meta-analysis.

Gender assignment in infants born with a difference in sexual development (DSD) remains one of the many difficult decisions faced by the multi-disciplinary treatment team as some of these children develop gender identity disorder (GID) when they become adults. In this systematic review and meta-analysis we have analyzed the prevalence of GID in adolescent and adults with DSD. The secondary outcome of this review is to help physicians in appropriate sex assignment of DSD children so that development of GID in later life can be reduced. METHODS: Pubmed/Index medicus were searched for "intersex" [All fields] OR "disorders of sexual differentiation AND "gender identity disorder OR gender dysphoria" [MeSH] for articles published between 2005 and 2020. Typical diagnoses included were congenital adrenal hyperplasia (CAH); complete androgen insensitivity syndrome (CAIS); partial androgen insensitivity syndrome (PAIS); 5 alpha reductase deficiency (5ARD); 17-hydroxysteroid dehydrogenase deficiency (17HSD); mixed gonadal dysgenesis (MGD) and complete gonadal dysgenesis (CGD). GID or gender dysphoria (a strong feeling of dissatisfaction about oneself as male or female) prevalence in DSD patients older than 12 years of age was extracted. Within each condition, GID percentage was compared between female and male rearing. RESULTS: The I2statistics for prevalence of GID in DSD showed high heterogeneity with I2 of 93% (95% C.I 90-95%) among the 20 articles included. The overall prevalence of GID among those with DSD was 15% (95% C.I 13-17%). CAH reared females had 4% GID while CAH reared males had significantly higher GID at 15% (p = 0.0056). All CAIS patients were raised as females and the prevalence of GID was 1.7%. GID prevalence was 12% in PAIS raised as females while 25% in those raised as males with no significant difference (p = 0.134). GID was significantly high in 5ARD (53%) and 17HSD (53%) reared as females with half of them virilizing at puberty forcing a gender change. Among sex chromosome DSD 22% of those reared as females had GID while none in those raised as male with no significant difference. CONCLUSIONS: GID is low in women with CAH, CAIS and CGD favoring female sex of rearing in these conditions. GID is high in women with 5ARD/17HSD favoring male sex of rearing in these conditions. GID is variable in PAIS or MGD and no recommendations on sex of rearing could be made in these conditions. Each DSD patient is unique and they warrant multi-disciplinary care and long term psycho sexual support.

The Nomogram of Clitoral Length and Width in Iranian Term and Preterm Neonates.

Background and Objectives: Clitoromegaly is an important parameter in the evaluation of ambiguous genitalia in neonates, but the normative data for clitoral size in newborns have racial/ethnic differences. The present study aimed to determine clitoral length (CL) and clitoral width (CW) values and establish cutoff measurement to define clitoromegaly in both term and preterm Iranian neonates for the first time. Methods: A total number of 580 female newborn infants delivered at 28-42 weeks of gestation were enrolled in the study, and their CL and CW were measured on the first 72 h of birth. Data about birth weight (BW), body length (BL), and head circumference (HC) of newborns; mothers' age; and gestational age (GA) were recorded, too. Results were presented as mean ± standard deviation (SD) for quantitative variables and were summarized by frequency (percentage) for categorical variables. Backward stepwise regression analysis was used for prediction of CL and CW. Results: Among 580 Iranian female newborns studied, 187 were term neonates and the other 393 newborns were preterm. Mean ± SD values of CL were 6.11 ± 0.39 mm in term infants and 5.45 ± 0.64 mm in preterm infants (P < 0.001). Mean ± SD values of CW were 4.22 ± 0.43 in term infants and 3.68 ± 0.53 in preterm infants (P < 0.001). Regression analysis showed that CL was correlated with GA considered by last menstrual period, BL, BW, and HC; and CW was associated with GA, BL, and BW. Conclusion: This study suggests normative values (mean + 1, 2, and 3 SD) of CL and CW according to GA, which can be used as a reference for Middle East's newborns, especially Iranian newborn babies.

Breast Cancer and Major Deviations of Genetic and Gender-related Structures and Function.

We have searched the literature for information on the risk of breast cancer (BC) in relation to gender, breast development, and gonadal function in the following 8 populations: 1) females with the Turner syndrome (45, XO); 2) females and males with congenital hypogonadotropic hypogonadism and the Kallmann syndrome; 3) pure gonadal dysgenesis (PGD) in genotypic and phenotypic females and genotypic males (Swyer syndrome); 4) males with the Klinefelter syndrome (47, XXY); 5) male-to-female transgender individuals; 6) female-to-male transgender individuals; 7) genotypic males, but phenotypic females with the complete androgen insensitivity syndrome, and 8) females with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (müllerian agenesis). Based on this search, we have drawn 3 major conclusions. First, the presence of a Y chromosome protects against the development of BC, even when female-size breasts and female-level estrogens are present. Second, without menstrual cycles, BC hardly occurs with an incidence comparable to males. There is a strong correlation between the lifetime number of menstrual cycles and the risk of BC. In our populations the BC risk in genetic females not exposed to progesterone (P4) is very low and comparable to males. Third, BC has been reported only once in genetic females with MRKH syndrome who have normal breasts and ovulating ovaries with normal levels of estrogens and P4. We hypothesize that the oncogenic glycoprotein WNT family member 4 is the link between the genetic cause of MRKH and the absence of BC women with MRKH syndrome.

Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development.

We present key points from the updated Dutch-Flemish guideline on comprehensive diagnostics in disorders/differences of sex development (DSD) that have not been widely addressed in the current (inter)national literature. These points are of interest to physicians working in DSD (expert) centres and to professionals who come across persons with a DSD but have no (or limited) experience in this area. The Dutch-Flemish guideline is based on internationally accepted principles. Recent initiatives striving for uniform high-quality care across Europe, and beyond, such as the completed COST action 1303 and the European Reference Network for rare endocrine conditions (EndoERN), have generated several excellent papers covering nearly all aspects of DSD. The Dutch-Flemish guideline follows these international consensus papers and covers a number of other topics relevant to daily practice. For instance, although next-generation sequencing (NGS)-based molecular diagnostics are becoming the gold standard for genetic evaluation, it can be difficult to prove variant causality or relate the genotype to the clinical presentation. Network formation and centralisation are essential to promote functional studies that assess the effects of genetic variants and to the correct histological assessment of gonadal material from DSD patients, as well as allowing for maximisation of expertise and possible cost reductions. The Dutch-Flemish guidelines uniquely address three aspects of DSD. First, we propose an algorithm for counselling and diagnostic evaluation when a DSD is suspected prenatally, a clinical situation that is becoming more common. Referral to ultrasound sonographers and obstetricians who are part of a DSD team is increasingly important here. Second, we pay special attention to healthcare professionals not working within a DSD centre as they are often the first to diagnose or suspect a DSD, but are not regularly exposed to DSDs and may have limited experience. Their thoughtful communication to patients, carers and colleagues, and the accessibility of protocols for first-line management and efficient referral are essential. Careful communication in the prenatal to neonatal period and the adolescent to adult transition are equally important and relatively under-reported in the literature. Third, we discuss the timing of (NGS-based) molecular diagnostics in the initial workup of new patients and in people with a diagnosis made solely on clinical grounds or those who had earlier genetic testing that is not compatible with current state-of-the-art diagnostics.

Observational study of disorders of sex development in Yaounde, Cameroon.

Introduction According to the current classification of the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society for Pediatric Endocrinology (ESPE) of Disorders of Sex Development (DSD), etiologies vary around the world. Ethnic or genetic diversity probably explains this variability. We therefore conducted the present study on etiologies of DSDs in a country from central Africa. Methods We carried out an observational retrospective study at the Pediatric Endocrinology Unit of the Mother and Child Centre of the Chantal Biya Foundation in Yaounde, Cameroon from May 2013 to December 2019. All patients diagnosed with a DSD were included, and incomplete files excluded. Results We included 80 patients diagnosed with DSD during the study period. The 46,XX DSD were the most frequent in our study population (n = 41, 51.25%), with congenital adrenal hyperplasia (CAH) as the main diagnosis. The 46,XY DSD accounted for 33.75% and sex chromosome DSD group represented 15% of the study population. Conclusions DSDs are not an exceptional diagnosis in a Sub-Saharan context. 46,XX DSD are the most prevalent diagnosis in our setting. The diagnosis of all these affections is late compared to other centers, justifying advocacy for neonatal screening of DSDs in our context.