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46,XY partial gonadal dysgenesis (PGD) is a rare cause of disorder of sexual development (DSD) and characterized by a range of testicular dysgenesis, ambiguous genitalia, and absent/rudimentary Müllerian structures 1,2.We present the surgical management of a 21-year-old patient with 46,XY PGD,who has predominantly female external genitalia with clitoral enlargement and complete vaginal agenesis. Our patient presented with primary amenorrhea and lack of breast development. Clitoral enlargement was present with a single urethral opening and absence of an external vaginal opening (Fig.1)Laboratory evaluation revealed low testosterone concentrations (0.3 ng/ml) with elevated FSH and LH leves.Total testosterone/dihydrotestosterone and androstenedione ratios were normal. While pelvic imaging showed no uterus and vagina, bilateral streak gonadal tissue were observed within the distal part of inguinal canals.The genetic evaluation showed a 46, XY karyotype with FISH analyses positive for the SRY gene.Detailed genetic analysis performed for a 46,XY DSD panel with targeted next generation sequencing (NGS) failed to reveal any identified mutation.Our patient was raised a female and expressed no gender identity confusion. Bilateral gonadectomy with open inguinal incisions, reduction clitoroplasy and McIndoe vaginoplasty were performed during the same session.The small dysgenetic gonads in the inguinal canals were determined preoperatively.Two full-thickness skin grafts were harvested from the bilateral inguinal incision. Reduction clitoroplasty was performed by reducing the corpus cavernosum while preserving the glans clitoris and neurovascular structures3.In the presence of a wide urethral opening without a vaginal introitus, creating the appropriate vaginal opening with a perineal approach was meticulously performed.The operation was completed by placing skin grafts into the created vaginal cavity.Pathological findings was significant for seminoma in the right testicle.A vaginal mold was left in place all day for the first 3 months and only at night for an additional 3 months. She was started on estrogen replacement for pubertal induction.Significant reduction in size of the glans and no vaginal stenosis were observed 3 months after the procedure (Fig.2). 46,XY DSD patients, especially those with genital ambiguity, are complex cases in terms of both clinical and surgical management. 46,XY PGD should be considered as a rare cause in these cases where other possible causes have been excluded. Achieving a good cosmetic result without functional loss requires a well-planned and meticulous surgical intervention. Creating a neovaginal space requires great care, especially in cases where there is no vaginal introitus. [ABSTRACT FROM AUTHOR]

46XY pure gonadal dysgenesis (Swyer syndrome) is a rare disorder of sexual development. Patients have a 46XY karyotype, though phenotypically they appear female with normal external genitalia and vagina. Although patients exhibit normal Müllerian structures (uterus, fallopian tubes, and vagina), they possess a pair of bilateral undifferentiated gonad streaks. Delayed puberty and primary amenorrhea are the common presentations. There is an increased risk of developing tumors in the gonads and therefore a bilateral gonadectomy is recommended. A 16-year-old girl who presented with primary amenorrhea was diagnosed with Swyer syndrome. She underwent prophylactic bilateral gonadectomy and salpingectomies. She was discovered to have no gonadal malignancy, conversely dysgerminoma solely within the fallopian tube. Both bilateral salpingectomies and bilateral gonadectomies should be recommended as the operation of choice in patients with Swyer Syndrome. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) mutations, which cause androgen insensitivity syndrome, impair the actions of 5α-dihydrotestosterone and testosterone, resulting in abnormal sexual development. In most cases, genetic aberrations of the AR are caused by substitutions, but also can result from mutations in splicing regions and deletions in the AR gene. Our present report describes a female patient with 46,XY karyotype and normal female external genitalia. A novel de novo c.1669_1670insC insertion in the AR gene caused androgen insensitivity syndrome. This report provides a detailed clinical characterization of the patient and a possible pathogenic mechanism leading to androgen insensitivity syndrome and should be particularly useful in genetic counseling. [ABSTRACT FROM AUTHOR]

A crucial part of patient management is effective delivery of unfavorable information, in a manner that will not affect future engagement with them, their coping strategies and their compliance to treatment. We present a case report detailing how to communicate a life-changing diagnosis to patients. Two siblings, aged 20 and 18, presented with primary amenorrhea to our Pediatric and Adolescent Gynecology Unit. They were female phenotype with 46XY karyotype. The elder sister had bilateral herniorrhaphy at 14 years with Breast Tanner 4, Pubic Hair Tanner 2, and normal female external genitalia. The younger one had left herniorrhaphy at 12 years, with Breast Tanner 3, Pubic Hair Tanner 1 and normal female external genitalia. They were accompanied by their mother unaware of their diagnosis. Our senior most clinician reviewed their laboratory and imaging results and led the diagnosis disclosure of Complete Androgen Insensitivity Syndrome to the siblings and their mother. Her opening statement was, "We are all different." She then explained the five factors that contribute to gender and then described their diagnosis, what it meant and how it came about. Further, she discussed the cultural and religious implication and informed them of support groups available. Despite the comprehensive discussion and the opportunity to ask questions at any point, the patients seemed perturbed by the news and remained silent. The clinic visit was finalized by answering the concerns raised by their mother and scheduling a follow-up appointment to allow for further conversation and debriefing. Bad news is information that has potential to negatively alter a patients view of their future. Both the process of breaking the news and the content have a profound effect on the patient therefore the delivery has to be well thought out. It is a critical advanced communication skill for clinicians. One can opt to use a non-structured approach, like we did, or employ predefined communication strategies on breaking bad news. One example of these frameworks is the SPIKES protocol: an acronym that details consideration of the Setting, Perception, Invitation, Knowledge, Empathy and Summary. Such protocols have been cited to improve clinicians confidence in breaking bad news and improve patient involvement in the decision-making process. However, effective communication must allow for deviations from the sequence to allow patient expression of emotions, rather than a strict focus on the process of breaking bad news. In addition, breaking bad news should not be seen as a singular event. As seen in our case, the revelation of the diagnosis can 'numb' the patients and hence require follow-up sessions to debrief and chart a care plan. [ABSTRACT FROM AUTHOR]

Infants with differences of sex development (DSD) are often diagnosed at birth due to ambiguous genitalia or incongruence between karyotype and external genitalia. In some cases, the degree of virilization varies significantly within the same condition. This can lead to confusion and distress with the gender assignment process, especially in the immediate postnatal period. This is a retrospective cohort study of patients presenting for care from 2007-2021 with a diagnosis of 45X/46XY or 46XX/46XY mixed gonadal dysgenesis (MGD) or 46XY complete gonadal dysgenesis (CGD), identified by ICD-9 and ICD-10 codes. These are two common DSD conditions with confusion around sex assignment at birth. Descriptive statistics were used to summarize the data. This study was IRB approved. Sixty-two patients met inclusion criteria and were included in the study, including 42 patients with MGD, 20 CGD. Of the patients with MGD, 48% were assigned male at birth and 52% female. No patients reported a gender identity incongruent with sex assigned at birth at the time of most recent clinic visit. The average age at most recent visit was 13 years (range 0-32 years). Of the male-assigned patients, 80% underwent hypospadias repair, the remainder had typical male external genitalia. The majority (16/22) of female-assigned patients had typical female external genitalia, 4 underwent feminizing genitoplasty, and 2 had clitoromegaly with no immediate plans for surgery. All surgeries were performed at age ≤5 years, except for one feminizing vaginoplasty which was performed at age 11 years. The two patients with clitoromegaly were age 1 and 12 years at the time of the last visit, respectively. Of the patients with CGD, 15% were assigned male at birth and 85% female. Similarly, no patients reported gender dysphoria. The average age at most recent visit was 15.7 years (range 0-30 years). Of the male patients, 2/3 underwent hypospadias repair and 1/3 had micropenis. Seventy-six percent of female patients had typical female external genitalia, 2 underwent feminizing genitoplasty, and 2 had clitoromegaly with no immediate plans for surgery. All surgeries were performed within two years of age. The two patients with clitoromegaly were age 2 and 30 years at time of last visit, respectively. Gender identity of all patients remained congruent throughout this study. Patients with increased virilization were likely to be assigned male sex and identify with male gender. Those with less virilization were more likely to identify as female. Parents can be counseled that with careful and thoughtful decision making in the newborn period, the potential for inappropriate sex assignment is low in children with MGD and CGD. [ABSTRACT FROM AUTHOR]

The case report describes the case of 16-year-old girl who came to the pediatric-gynecologist's for primary amenorrhea. She was of normal height 155 cm, with female external genitalia, secondary sexual characteristics according to Tanner M2,A3,Ph 4. In ultrasound we detected uterus of infantile type, without endometrium, ovaries not visualized. In functional cytology was only basal and para-basal cells. As part of the differential diagnosis of primary amenorrhea were taken a hormonal profile, genetic examination. In the laboratory was diagnosed hypergonadotropic hypogonadism, in genetic examination mosaic karyotype 45 × 0/46XY. Concluded as mixed gonadal dysgenesis syndrome. Induction of puberty started by the gynecologist with estrogens. Due to the karyotype, bilateral laparoscopic adnexectomy is indicated as prevention of tumor transformation of dysgenetic gonads, especially of gonadoblastoma. Intraoperatively striated gonads were removed. Continued induction of puberty with estrogens, added progestogens after sufficient growth. After hormonal stimulation, the patient menstruates. Plan to continue combined hormonal contraception. In the future, when planning a pregnancy, it is necessary to use methods of assisted reproduction with a donated oocyt. Mixed gonadal dysgenesis is one of the possible causes of primary amenorrhoea with an incidence of 1:15,000 live births. Its diagnosis is possible only with the help of genetic testing. [ABSTRACT FROM AUTHOR]