Ali et al. J Med Case Reports (2021) 15:362 https://doi.org/10.1186/s13256-021-02914-2 CASE REPORT Open Access Ambiguous genitalia: clinical management of adult female with male assigned gender: a case report Mahamudu Ayamba Ali1,2, Raymond Saa‑Eru Maalman1, Yaw Otchere Donkor1* and James Edward Mensah3,4 Abstract Background: Disorders of sex development are anomalies in which the development of urogenital ridge is undif‑ ferentiated for the male and female child. Imaging plays a vital role in investigating the gross anatomy and associated anomalies. Ultrasonography, such as genitography and magnetic resonance, is the primary modality for demonstrat‑ ing internal gonads and genitalia. Early multidisciplinary approach in the management of ambiguous genitalia includ‑ ing early surgical intervention is the predominant practice, with few current considerations on deferral of genital reconstruction until adolescent age. Case presentation: We report the rare case of a 24‑year‑old adult female from a majority ethnic group of the Volta region, Ghana who was diagnosed and raised as male, now requiring surgical restoration to the female gender. The surgical team decided to assign external genitalia to correspond with the already intact internal organs, thus con‑ structing the vulva. Consent was given by the client and her family members for management and surgical interven‑ tion. The surgery was scheduled and duly performed with a successful outcome. Understanding and consent was sought from the patient for the purpose of using her images for teaching, scientific publication, and demonstrations. Conclusion: The advantages of deferring surgical reconstruction with psychological counseling after early assess‑ ment need to be considered to prevent inappropriate gender assignment. Keywords: Disorders of sex development, Ambiguous genitalia, Clinical management, Surgical approach, Adult female Background sex is atypical [4, 5], and before 2006, DSD was termed as The term ambiguous genitalia describes the most com- intersex [2]. Based on the karyotype, three main groups mon clinical presentation of a variety of congenital con- of DSDs are identified using the new nomenclature pro- ditions classified as disorders of sexual development posed by the Chicago Consensus (Table 1). (DSD) or differences in sex development [1, 2]. DSDs Disorders of sex development are a major pediatric are associated with atypical development of the internal issue, accounting for approximately 1% of all live births and external genital structures as a result of variations in [5]. However, the incidence varies between developed genes, developmental programming, and hormones [3]. and developing countries [6]. In Ghana, there is a pau- DSDs occur when chromosomal, gonadal, or anatomical city of information, but in other developing countries such as Saudi Arabia incidence is reported as 1 in 2500 live births and in Egypt 1 in 3000 live births [2, 6]. In a *Correspondence: dotchere@uhas.edu.gh 1 developed country such as Germany, the incidence is Department of Basic Medical Sciences, School of Medicine, University of Health and Allied Sciences, Ho, Volta Region, Ghana as low as 2 per 10,000 live births. The high rate of DSD Full list of author information is available at the end of the article was hypothesized to result from higher consanguinity © The Author(s) 2021. 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J Med Case Reports (2021) 15:362 Page 2 of 5 Table 1 Disorders of sex development: Chicago Classification of sex [4] Sex chromosome DSD 46, XY DSD 46, XX DSD 45, XO (Turner syndrome and variants) Disorders of gonadal (testicular) development Disorders of gonadal (ovarian) development Complete gonadal dysgenesis (Sawyer syndrome) Ovotesticular DSD Partial gonadal dysgenesis, gonadal regression, ovotesticu‑ Testicular DSD (SRY+, dup SOX9) lar DSD • Gonadal dysgenesis 47, XXY (Klinefelter syndrome and variants) Disorders in androgen synthesis or action • Androgen Androgen excess biosynthesis defect (17‑hydroxysteroid dehydrogenase Fetal (21‑or 11‑hydroxylase deficiency) deficiency, 5α‑reductase deficiency) 45, X/46, XY (mixed gonadal dysgenesis, Defect in androgen action (complete androgen insensitivity Fetoplacental (aromatase deficiency, P450 ovotesticular DSD) syndrome) oxidoreductase) 46, XX/46, XY (chimeric, ovotesticular DSD) LH receptor defects (Leydig cell hypoplasia) Maternal (luteoma, exogenous) Disorders of AMH and AMH receptor (persistent Müllerian duct syndrome) DSD: Disorders of Sex development, LH: Luthenizing hormone, AMH: Antimulerian hormone, SRY: Sex region Y chromosome among populations of developing countries than in the diagnosis as well as management of DSDs, as in among those from developed countries [2]. The under- the case reported herein. lying cause of ambiguous genitalia in a newborn/child needs extensive and urgent investigation to avoid Case presentation missing a life-threatening problem such as congenital A 24-year-old from a majority ethnicity of Volta region adrenal hyperplasia (CAH), which is a major presenta- Ghana was referred on account of 7 years cyclical total tion of DSD [2]. painless hematuria, which lasted about 2–3  days per Clinical management of DSDs is carried out per the episode for the past 3 years. This was often preceded by classification proposed by the Paediatric Endocrinol- mild lower abdominal pain and malaise. There was no ogy Society Lawson Wilkins and the European Society identifiable risk factor for bladder carcinoma (habits or of Paediatric Endocrinology [7]. The management of exposure). The patient is the eldest of five siblings, who patients with DSD and related conditions is focused on are all alive and had normal pregnancy and delivery peri- four aspects: (1) etiological diagnosis, (2) assignment ods. The mother was on the routine antenatal medica- of gender, (3) indication for and timing of genital sur- tions as always prescribed in Ghana. Two of her siblings gery, and (4) disclosure of medical information to the also had a similar genital appearance and were undergo- patient [8]. Thorough clinical, hormonal, radiological, ing medical examinations. She was christened and raised chromosomal, and molecular evaluations are there- as a male from infancy to adolescence when she noticed fore essential. However, a prompt evaluation of these the development of female secondary sexual character- assignments may be challenging for accurate diagno- istics (breast, changes in voice, hair distribution pattern, sis and appropriate therapy, especially in resource- and general hip enlargement). She stopped her educa- deprived countries. Satisfactory management of these tion and migrated to the city where she has been residing children does not merely demand early diagnosis and since then. Physical examination reveals feminine figure appropriate treatment, but gender assignment will appearance, well-developed breast, female hair distribu- produce a positive impact on the outcome. Failure of tion pattern, and a feminine voice. She had a mega clit- the appropriate approach causes great discomfort for oris without vaginal opening (Fig.  1), and the vagina or family and healthcare providers [9]. labial/scrotal area shows a solid perineal mass. The ure- Genetic tools such as microarray analyses and next- thral opening was underneath the clitoris (Fig. 2). generation sequencing techniques have identified novel genetic variants among patients with DSD. Most Management of the case importantly, patient management needs to be indi- The management of the DSD in this case was focused vidualized especially for decisions related to the sex on first ascertaining the etiological diagnosis. This of rearing, surgical interventions, hormone treatment, was done by performing an abdominopelvic ultra- and potential for fertility preservation [3]. In countries sound scan, which showed normal uterus and ova- with an inadequate health system, there are challenges ries. Urethrocystoscopy demonstrated a normal bladder mucosa, ureteric orifices, and a poorly Ali et al. J Med Case Reports (2021) 15:362 Page 3 of 5 Fig. 1 A mega clitoris without vaginal opening Fig. 3 Vaginal and urethral catheters during separation Fig. 2 Mega clitoris with hypospadias visualized dimple in the urethral mucosa distal to the sphincter. A diagnosis of 46, XX DSD secondary to androgen excess was made (Table  1). Since all the internal female genital organs were found to be nor- Fig. 4 Post vaginoplasty and neoclitoroplasty mal, the second decision of the surgical team was the assignment of the external genitalia to correspond with the internal organs; thus, construction of the vulva separation, vaginoplasty, and neoclitoroplasty, as seen was indicated (Fig. 3). The client and her family were in Figs.  3 and 4. The patient’s follow-ups and review informed of the diagnosis and the treatment option after treatment were scheduled for monitoring of the arrived at by the team. Consent was given by the client aftermath of the surgery. Her review revealed that the and her family members in a signed form. The surgery procedure had been successful, with no adverse event. was scheduled and duly performed with successful Understanding and consent were sought from the Ali et al. J Med Case Reports (2021) 15:362 Page 4 of 5 patient for the purposes of using her images for teach- 4. There is an advantage to conducting a limited inves- ing, scientific publication, and demonstrations. tigation (concentrating on the urogenital area and internal organs) since secondary sexual features have Discussion already developed and directed the biological gender, The formation of a typical male or female sex organ especially in hospitals with limited diagnostic abili- involves numerous and complex genetic and physiologi- ties. cal events such as sex determination during fertilization, 5. It demonstrates the relative ease of surgical interven- development at the gonadal ridge, expression of the mes- tion as a result of well-developed structures at the onephric or paramesonephric ducts, differentiation into perineal area for dissection and raising of flaps dur- internal and external organs during the zygotic phase, ing vaginoplasty and neoclitoroplasty. growth of these reproductive organs to phenotypic rec- 6. It shows reduced postoperative complications in ognition, and masculinization or feminization from birth terms of infections and reconstructive breakdown. to puberty under the influence of hormones and tran- 7. It resulted in good functional outcome and patient scription factors [10, 11]. satisfaction. Managing an adult with ambiguous external genita- lia requiring surgical intervention is extremely rare as patients with various spectra of the disease requiring surgical intervention most probably would have received Conclusion it during childhood or adolescence [12, 13]. The current The advantages of deferring surgical reconstruction practice for managing these diseases is an early multi- with psychological counseling after early assessment disciplinary approach that often includes early surgical need to be considered to prevent inappropriate gender evaluation and possible reconstruction, at most deferring assignment. until adolescence [14]. The early approach in assigning gender is influenced by the desire to limit identity crisis, Abbreviations which is believed to help reduce parental anxiety, satisfy DSDs: Disorders of sex development; CAH: Congenital adrenal hyperplasia. some unique sex-related cultural practices, and above all, help in the sociocultural growth of the child [14]. Acknowledgements Authors are grateful and duly acknowledge Margaret Marquart Catholic Advocates for deferral of surgical intervention raise Hospital, Kpando, Ghana nurses, and all medical team for the opportunity and concern that the influence of high maternal estrogen lev- support. We are also thankful to the patient for having confidence in us for a els that causes clitoromegaly could be mistaken for male successful outcome. phallus, leading to wrong gender assignment. Continuous Authors’ contributions psychological counseling while delaying vaginoplasty is All authors participated in the design of the study, acquired data, performed currently considered. This approach is believed to allow literature review, drafted the manuscript, and edited the manuscript. Dr. Ali Ayamba and Dr. James Mensah helped in the patient’s management. All for tissue growth that will make surgery relatively easy. authors read and approved the final manuscript. Full patient participation in the evaluation and treatment, as in this case under review, is critical. The optimal tim- Funding The authors have no funding to declare. ing of the surgery remains unclear. This case report has taught us many lessons associated with the timing of Availability of data and materials DSD management, including: The published information is available from the corresponding author on reasonable request. 1. It confirms the difficulty associated with early bio- Declarations logical sex determination among ambiguous genitalia neonates. Ethics approval and consent to participate 2. It lays out the social consequences of raising a child This study was conducted in accordance with the fundamental principles of the Declaration of Helsinki. This is a retrospective report of a successful with a wrong gender, including predisposition to bul- management of DSDs. Thus, ethical approval and consent to participate are lying and mockery by peers, withdrawal from school, not applicable. need for relocation, and change of name and dressing Consent for publication style when the secondary sex organs become promi- Written informed consent was obtained from the patient for the publica‑ nent. tion of this case report and any accompanying images. A copy of the written 3. It emphasizes the heightened anxiety of the patient consent is available for review by the Editor‑in‑Chief of this journal. and relatives over the delay in correction and the Competing interests need for prolonging psychological counseling if a The authors declare that they have no competing interests. delay is contemplated. Ali et al. J Med Case Reports (2021) 15:362 Page 5 of 5 Author details 7. García‑Acero M, Moreno O, Suárez F, Rojas A. Disorders of sexual develop‑ 1 Department of Basic Medical Sciences, School of Medicine, University ment: current status and progress in the diagnostic approach. Cur Urol. of Health and Allied Sciences, Ho, Volta Region, Ghana. 2 Consultant Urologist, 2019;13(4):169–78. Department of Surgery, School of Medicine, University of Health and Allied 8. Öcal G, Berberoğlu M, Şiklar Z, Bilir P, Uslu R, Yağmurlu A, Tükün A, Akar N, Sciences, Ho, Volta Region, Ghana. 3 Consultant Urologist, Department of Sur‑ Soygür T, Gültan S, Gedik VT. 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