Unexpected Diagnosis of Complete Androgen Insensitivity Syndrome (CAIS) During Inguinal Hernia Repair in 11-year-old-girl

Complete Androgen Insensitivity Syndrome (CAIS) is an X-link recessive genetic mutation of androgen receptor (AR) gene leading to complete inability of cell to respond to the androgens. CAIS occurs in 1 out of 20,400 XY live-birth babies, and affects about 1–2% of prepubertal girls that present with an inguinal hernia. Although individuals with CAIS have XY, those with grades 6 and 7 on the Quigley scale are born phenotypically female, without any signs of genital masculinization. Thus, individuals affected by CAIS develop a normal external female phenotype with normal female external genitalia, well-developed breast, absent uterus, and bilateral undescended testicles. The question of CAIS diagnosis does not come forward until the absent menses at the puberty is noted or accidentally during an inguinal hernia repair in a premenarchal girl. The present study reports a case of inguinal hernia repair on 11year-old girl, which led to unexpected intraoperative notion of CAIS. The diagnostic work-up, genetic counseling, sex assignment, and the need for preoperative CAIS screening in girls with bilateral inguinal hernia are described and discussed.


Introduction
Complete Androgen Insensitivity Syndrome (CAIS) is a rare disorder of sex development (DSD). It is manifested due to mutation in androgen receptor (AR) gene which has been mapped to Xq11-12 [1]. AR gene mutation is maternally inherited in 70% of the cases, whereas the remaining 30% are de novo mutations. The disease is characterized by feminization of external genitalia and bilateral undescended testes in a 46,XY individual [2].
Although, CAIS is easily diagnosed after puberty, it can be seen accidentally during surgical repair in girls with bilateral inguinal hernia. However, controversy exists about the need to screen premenstrual girls with bilateral inguinal hernia, the best methods of the screening, and the suitable time for gonadectomy. This report describes unexpected intraoperative findings (testis) during a repair of inguinal hernia in 11-year-old girl, which was later diagnosed as CAIS.  at the age of early adolescence. However, her expected removal of gonads will be explained on the lines of hernial repair. She should be taken in confidence when she is over 18 years old with the help of her parents and a religious leader. Professional news breaking should be exercised to her and further to whoever would marry her that she will not bear children.

Discussion
The aforementioned case represents the dramatic scenario of intraoperative finding It has been suggested that all premenstrual girls with inguinal hernias should undergo chromosomal study to rule out the possibility of an early diagnosis of CAIS [3]. This idea originates from the increased prevalence (0.8-2.4%) of CAIS in phenotypic females presenting with inguinal hernias [4]. Contrastingly, other authors argue that the 2.4% prevalence does not justify chromosomal screening since the vast majority (>97%) of phenotypic female cases presenting with inguinal hernia are less likely to have CAIS.
Moreover, in areas with limited health resources such as Africa, screening methods such as sonography and/or chromosomal analysis are not available or otherwise are very costly. In fact, the reported incidence of CAIS has not been convincing enough to support the routine use of such investigations even if they are available [5]. This view is supported by Hurme et al.'s study in which they diagnosed CAIS in only one case following karyotype analyses of 109 premenstrual females who had undergone inguinal hernia repair [6]. In fact, most authors agree on the unnecessity for chromosome analysis in girls with inguinal hernia and instead consider ultrasonography capable of revealing the uterus and/or the ovaries in most cases [7].
Considering Sudanese culture on sex assignment and orientation in rural community, parents easily accepted the decision not to reassign an opposite sex to the patient.This was evident in the unusual management in this reported case, where both parents were adamantly demanding early gonadectomy. The fear of social stigma may justify the concern of the parents stressing the surgeon to comply and perform early gonadectomy.
According to the statistics, most of the patients with CAIS present late with primary amenorrhea leading to delayed diagnosis, in some cases, post marriage. In fact, early diagnosis may help appropriate scheduling of gonadectomy as well as systematic parental counseling regarding several long-term issues of hormone-replacement therapy and fertility [8,9]. Early diagnosis of CAIS is equally essential for better management of psychosocial comorbidities and genetic counseling including carrier detection and pre-implantation genetic test with 100% chance for carrier females to bear healthy children; putting end to the transmission of the mutated X chromosome to the coming generations.