patient [69].
Bladder
If the sub‐umbilical portion of the anterior abdominal wall fails to meet in the midline above the genital tubercles, the anterior bladder wall is partially or completely absent, leading to incomplete or total bladder exstrophy. It is always associated with epispadias and other abnormalities of the external genitalia. The clitoral bodies are bifid, and the mons pubis and labia protrude anteriorly. The vaginal introitus is situated anteriorly and is frequently stenosed. Magnetic resonance imaging can be very helpful in identifying the anatomical abnormalities and is used prior to surgery, which is usually done in stages [70,71]. Most patients require vaginoplasty in the teenage years.
A more severe form of this structural defect is cloacal exstrophy, in which there are defects of the urorectal structures, bladder, and terminal gastrointestinal tract [72]. Advances in neonatal surgery can now result in survival rates of up to 100%, and guidelines exist for management which should be undertaken by specialist multidisciplinary teams [73].
Urethra
Failure of the urogenital septum to reach the cloacal membrane leaves the urethra, vagina, and rectum converging into a single channel with a solitary opening on to the perineum.
Congenital abnormalities of the urethra are much less common in females than in males, but duplication of the urethra is a cause of incontinence. The accessory urethra usually arises from the trigone of the bladder and opens onto the anterior wall of the vagina. Mild forms of epispadias may occur in the female, giving rise to disturbance of bladder control and urinary incontinence. The urethral opening lies deep to the mons, and a bifid clitoris is seen [74]. Hypospadias in the female occurs in association with 46,XX DSD. In both epispadias and hypospadias, the female urethra is congenitally short [75]. Meatal stenosis is uncommon in females but can mimic bladder neck obstruction, and urethral cysts of the para‐urethral Skene’s glands can lead to recurrent urinary symptoms. A prolapse of the urethral mucosa occurs only in females [76]. An ectopic ureter may open into the urethra, and any of these urethral abnormalities may present with urinary incontinence, which leads to an irritant contact vulval dermatitis.
Vulval and intestinal abnormalities
A perineal groove is a rare ano‐perineal malformation, but the cause is unclear. It may be due to a failure of the genital folds to fuse or a defect in the urorectal septum. Exposed mucosa extends from the fourchette to the anus and most resolve spontaneously [77]. An imperforate anus or anal stenosis may be associated with a variety of abnormalities of the genital tract and vulva [78]. An ectopic opening of the lower gastrointestinal tract may be found in the vagina or elsewhere in the perineum. When a rectovaginal fistula is formed, there are often urinary tract abnormalities present as well [79].
Patient Support Groups
Turner Syndrome Foundation
www.turnersyndromefoundation.org
Turner Syndrome Support Society
Turner Syndrome Society of the United States
Disorders of sexual differentiation
MRKH UK
Congenital adrenal hyperplasia
Last accessed September 2021.
References
1 2 Biason‐Lauber, A. WnT4, RSPO1 and FoxL2 in sex development. Semin Reprod Med. 2012; 30(5): 387–395.
2 3 Wilhelm, D., Palmer, S. and Koopman, P. Sex determination and gonadal development in mammals. Physiol Rev. 2007; 87: 1–28.
3 4 Mullen, R.D. and Behringer, R.R. Molecular genetics of Mullerian duct formation, regression and differentiation. Sex Dev. 2014; 8: 281–296.
4 5 Sajjad, Y. Development of the genital ducts and external genitalia in the early human embryo. J Obstet Gynecol Res. 2010; 36: 929–937.
5 6 O’Rahilly, R. and Muller, F. Developmental Stages in Human Embryos. 1987. Carnegie Institution of Washington, Washington DC.
6 18 Cunha, G.R., Cao, T.K., Shen, M. and Robboy, S.L. Molecular mechanisms of development of the human fetal female reproductive tract. Differentiation. 2017; 97: 54–72.
7 19 Robboy, S.J., Karita, T., Baskin, L. and Cunha, G.R. New insights into human female reproductive tract development. Differentiation. 2017; 97: 9–22.
8 21 Witchel, S.F. Disorders of sex development. Best Pract Res Clin Obstet Gynecol. 2018; 48: 90–102.
9 22 Creighton, S., Chernausek, S.D., Romao, R. et al. Timing and nature of reconstructive surgery for disorders of sex development. J Paediatr Urol. 2012; 8: 602–610.
10 23 Ahmed, S.F., Achermann, J.C., Avit, W. et al. Society for Endocrinology UK guidance on the initial evaluation of an infant or adolescent with a suspected disorder of sexual development (Revised 2015). Clin Endocrinol. 2016; 84(5): 771–788.
11 24 Hughes, I.A. Disorders of sexual development: New definition and classification. Best Pract Res Clin Endocrinol Metab. 2008; 22: 119–134.
12 26 Mavridi, A., Ntali, G., Theodora, M. et al. A spontaneous pregnancy in a patient with Turner syndrome with 45,X/47,XXX mosaicism: A case report and review of the literature. J Pediatr Adolesc Gynecol. 2018; 31(6): 651–654.
13 27 Gravholt, C.H., Viuff, M.H., Brun, S. et al. Turner syndrome: Mechanisms and management. Nat Rev Endocrinol. 2019; 15(10): 601–614.
14 28 Gravholt, C.H., Andersen, N.H., Conway, G.S. et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: Proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017; 177(3): G1–G70.
15 29 Schoemaker, M.J., Swerdlow, A.J., Higgins, C.D. et al. Cancer incidence in women with Turner syndrome in Great Britain: A national cohort study. Lancet Oncol. 2008; 9: 239–246.
16 30 Matsumoto, F., Matsuyama, S., Matsui, F. et al. Variation of Gonadal dysgenesis and Tumor risk in patients with 45,X/46, XY mosaicism. Urology. 2020; 137: 157–160.
17 33 Falhammar, H., Frisén, L., Hirschberg, A.L. et al. Increased cardiovascular and metabolic morbidity in patients with 21‐hydroxylase deficiency: A Swedish population‐Based National Cohort Study. J Clin Endocrinol Metab. 2015; 100(9): 3520–3528.
18 36 Conlon, J.L. Diethylstilbestrol: Potential health risks for women exposed in utero and their offspring. JAAPA. 2017; 30(2): 49–52.
19 37 Brunskill, P.J. The effects of fetal exposure to danazol. Br J Obstet Gynaecol. 1992; 99(3): 212–215.
20 39 Xue, M., Wang, X., Li, C. et al. Novel pathogenic mutations in disorders of sex development associated genes cause 46,XY complete gonadal dysgenesis. Gene. 2019; 718: 144072.
21 42 Oppelt, P.G., Lermann, J., Strick, R. et al. Malformations in a cohort of 284 women with Mayer‐Rokitansky‐Küster‐Hauser (MRKH) syndrome. Reprod Biol Endocrinol. 2012; 10: 57.
22 43 Rall, K., Eisenbeis, S., Henninger, V. et al. Typical and atypical associated findings in a group of