Müllerian Agenesis in a patient with Rubinstein-Taybi Syndrome: A Case Series and Review of the Overlapping Developmental Biologic Pathways.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multi-system neurodevelopmental condition caused by deficiency of CREBBP (16p13.3) or EP300 (22q13.2). Müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, is defined as congenital agenesis of the uterus, cervix, and upper vagina without a definite genetic cause. INDEX CASE AND CASE SERIES: We present a 14-year-old female with RSTS type 1 (CREBBP, c.4395-2A>C) and MRKH, the first documented in the literature. Following presentation to Gynecology for anticipatory guidance regarding future menstrual suppression and follow-up of previously diagnosed labial adhesions, exam under anesthesia revealed a single urogenital opening with cystoscopy demonstrating a normal urethra and bladder. Laboratory evaluation was consistent with peripubertal female gonadotropins and estradiol, 46,XX karyotype, and normal microarray, and a pelvic MRI confirmed Müllerian agenesis. Given this case, we assessed our cohort of females with RSTS and found that 4 of 12 individuals also had Müllerian anomalies. CONCLUSION: Gynecologic evaluation should be a part of medical care for females with RSTS, particularly in individuals with delayed menarche or abnormal menstrual history, on the basis of the observed association between RSTS and Müllerian anomalies in this case series. Although several candidate genes and copy number variants are associated with MRKH, no candidate genes in close proximity to the 16p13.3 region have been identified to explain both RSTS and MRKH in the index patient. Due to the regulatory nature of CREBBP during embryonic development, we theorize that CREBBP may play a role in the migration of Müllerian structures during embryogenesis.

International Experiences with Vaginal Lengthening Treatment Among Individuals with Müllerian Agenesis: A Mixed-Methods Study.

STUDY OBJECTIVE: To understand variations and experiences of vaginal lengthening internationally in individuals with congenital underdevelopment of the uterus, cervix, and upper vagina or Müllerian agenesis METHODS: In this study, we used a cross-sectional mixed-methods design incorporating quantitative and qualitative questionnaires. Adults with Müllerian agenesis completed questionnaires with quantitative and open-ended qualitative questions about their vaginal lengthening experiences. Data were analyzed using descriptive statistics and inductive thematic analysis. RESULTS: Of 616 respondents meeting inclusion criteria (representing 40 countries), 46% (n = 284) reported no vaginal lengthening intervention. Vaginal lengthening was commonly reported by participants from North America and Europe (59%) and less commonly by participants from Africa, Asia, and South America (16%). Of those who had undergone vaginal lengthening, 72% reported dilator use, 34% coital dilation, and 39% surgery. Four major themes were identified in response to the open-ended vaginal lengthening experience question: (1) difficult physical symptoms, (2) practical and psychosocial challenges, (3) intimate relationships and sexual satisfaction, and (4) impact of experiences with healthcare providers. CONCLUSION: This study highlights vaginal lengthening practices internationally and shared themes related to significant challenges and positive experiences. The findings show room for improvement in the counseling and care surrounding vaginal lengthening. Future research should investigate factors that influence decision-making about vaginal lengthening and work toward international consensus on best care practices in Müllerian agenesis.

Multidisciplinary Clinical Considerations in the Treatment of Pediatric Epithelial Ovarian Cancer.

BACKGROUND: Epithelial ovarian cancers are a rare subset of the less than 1% of ovarian cancers diagnosed in children. This case highlights considerations when caring for these patients. CASE: Evaluation of a 12-year-old postmenarchal girl who presented with suprapubic pain revealed a solid/cystic pelvic mass involving bilateral adnexa and elevated Cancer Antigen 125 (CA-125) level. Diagnostic laparoscopy pathology confirmed low-grade papillary serous ovarian carcinoma. Treatment involved surgical tumor debulking, hysterectomy, bilateral salpingo-oophorectomy, and omentectomy; adjuvant chemotherapy with no residual disease, and normalization of Cancer Antigen 125 (CA-125) level; and an aromatase inhibitor for maintenance. SUMMARY AND CONCLUSION: In children with adult-type gynecologic cancers necessitating treatments including surgical sterilization and hormone-modulating therapy, psychological support and developmentally informed collaboration between adult and pediatric services is essential. Clinical decisions for long-term bone and sexual health present opportunities for future research.

Prevalence of urinary, prolapse, and bowel symptoms in Mayer-Rokitansky-Küster-Hauser syndrome.

BACKGROUND: Müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser syndrome, occurs in 1 in 4500 to 5000 individuals assigned female sex at birth. Pelvic floor symptoms among individuals with Mayer-Rokitansky-Küster-Hauser syndrome have not been well studied, and it is unknown how vaginal lengthening treatments affect these symptoms. OBJECTIVE: This study aimed to assess urinary, prolapse, and bowel symptoms in individuals with Mayer-Rokitansky-Küster-Hauser syndrome and to determine whether symptoms vary by vaginal lengthening treatment. STUDY DESIGN: We conducted a cross-sectional study in 2019 using an online survey distributed by the Beautiful You MRKH Foundation via social media to individuals with Mayer-Rokitansky-Küster-Hauser syndrome. Demographics, age at and timing of diagnosis, information about vaginal lengthening treatment, urinary symptoms (Michigan Incontinence Symptom Index), prolapse symptoms (Pelvic Organ Prolapse Distress Inventory short-form version), and bowel symptoms (Bristol Stool Form Scale) were obtained. The inclusion criteria included self-reported diagnosis of müllerian agenesis and female sex. Respondents with a history of renal transplant or dialysis, completion of <85% of the survey, and non-English survey responses were excluded. Descriptive analyses were used to describe the sample population. Logistic regression, Kruskal-Wallis, and Fisher exact tests were used to compare the prevalence of pelvic floor symptoms and vaginal lengthening treatments. Associations between age and genitourinary symptoms were investigated with Spearman correlations. RESULTS: Of 808 respondents, 615 met the inclusion criteria, representing 40 countries. 81% of respondents identified as white. The median age of the participants was 29 years (interquartile range, 24-36), with a median age at diagnosis of 16 years (interquartile range, 15-17). Among the 614 respondents, 331 (54%) had vaginal lengthening treatment, 130 of whom (39%) had undergone surgical vaginal lengthening. Of individuals with Mayer-Rokitansky-Küster-Hauser syndrome, 428 of 614 (70%) reported having had one or more urinary symptoms, and 339 of 428 (79%) reported being bothered by these symptoms. Urinary symptoms included urinary incontinence (210 of 614 [34%]), urinary frequency (245 of 614 [40%]), urinary urgency (248 of 614 [40%]), pain with urination (97 of 614 [16%]), and recurrent urinary tract infections (177 of 614 [29%]). Prolapse symptoms included lower abdominal pressure (248 of 612 [41%]), pelvic heaviness or dullness (177 of 610 [29%]), and vaginal bulge (68 of 609 [11%]). In addition, constipation was reported by 153 of 611 respondents (25%), and anal incontinence was reported by 153 of 608 (25%) respondents. Beside recent urinary incontinence (P=.003) and anal incontinence (P<.001), the prevalence of pelvic floor symptoms (P>.05) did not differ significantly between those with and without vaginal lengthening. Among those with surgical vaginal lengthening, symptomatic vaginal bulge was highest in individuals who underwent a bowel vaginoplasty procedure. CONCLUSION: Urinary, prolapse, and bowel symptoms are common among individuals with Mayer-Rokitansky-Küster-Hauser syndrome and should be evaluated in this population. Overall, compared with no vaginal lengthening treatment, having vaginal lengthening treatment is not associated with substantial differences in the prevalence of pelvic floor symptoms, with the exception of recent urinary incontinence and anal incontinence. Our data suggested that bowel vaginoplasty may be associated with greater symptoms of vaginal bulge. More robust studies are needed to determine the impact of various vaginal lengthening treatments on pelvic floor symptoms.

Interdisciplinary Care and a Focus on Fertility Preservation When Multi-cystic Ovaries Cause Ovarian Torsion: A Case of a 9-year-old Girl with Severe, Undiagnosed Hypothyroidism.

BACKGROUND: Ovarian torsion can occur in Van Wyk Grumbach syndrome, a disorder characterized by severe primary hypothyroidism and ovarian enlargement. To date, all documented cases of torsion in this setting describe oophorectomy, which has significant hormonal and fertility implications. CASE: A 9-year-old pubertal girl presented to the emergency room with abdominal pain. Magnetic resonance imaging demonstrated bilateral, multi-cystic ovaries. Operative laparoscopy confirmed unilateral adnexal torsion, and detorsion without oophorectomy was accomplished. Postoperative laboratory tests revealed severe primary hypothyroidism. Ovarian size was reduced with hormone replacement therapy. SUMMARY AND CONCLUSION: This case demonstrates that prompt interdisciplinary intervention and awareness of severe hypothyroidism as a cause of ovarian torsion related to enlarged, multi-cystic ovaries may reduce the rate of oophorectomy, allowing preservation of pediatric patients' future fertility, and reducing morbidity postoperatively through prompt, long-term thyroid supplementation.

Outpatient Management of Heavy Menstrual Bleeding in Adolescent and Young Women with Inherited Platelet Function Disorders.

STUDY OBJECTIVE: To assess the treatment patterns and efficacy of hormonal (HM) and non-HM (NHM) management of heavy menstrual bleeding (HMB) in young women with inherited platelet function disorders (IPFDs). DESIGN, SETTING, AND PARTICIPANTS: A retrospective chart review was performed of outpatient treatment of HMB in female patients age 9-25 years who were diagnosed with IPFDs and referred to gynecology and/or hematology at a tertiary care hospital between 2006 and 2018. INTERVENTIONS: The study sample was identified using billing codes for IPFDs. Data on HM and NHM treatments and outcomes over a one- to two-year period were collected. Initial treatment was defined as the first treatment prescribed after referral. Descriptive statistics, Pearson χ2, and t tests were used for analysis. MAIN OUTCOME MEASURES: Treatment failure was defined as a change in treatment method because of continued bleeding. RESULTS: Thirty-four girls met inclusion criteria. After their initial visit, 19/34 (56%) were treated with HM, 12/34 (35%) with NHM, 2/34 (6%) with a combination of methods, and 1/34 (3%) were untreated. Initial treatment failed in 19/34 (56%) and those patients subsequently required a mean of 2 additional treatments during follow-up. Of the 34 included, 6/34 (18%) remained uncontrolled despite numerous treatment changes and 2/34 (6%) because of noncompliance. When control was achieved, 7/26 (27%) of patients were receiving combined oral contraceptives and 6/26 (23%) desmopressin acetate. CONCLUSION: HMB in girls with IPFDs can be difficult to control despite ongoing follow-up and treatment changes. Although the most effective treatment for HMB in young women with IPFDs was not identified, these findings will help providers and patients with setting expectations. Prospective studies are needed to develop recommendations on best practices.

Prolonged Vaginal Bleeding in an Adolescent Secondary to a Foreign Body: Need for a Comprehensive Assessment and Complex Surgery.

BACKGROUND: Heavy, prolonged menstrual bleeding is common in adolescents and results from a variety of etiologies. CASE: A 13-year-old, virginal girl was referred for prolonged, heavy vaginal bleeding despite combined oral contraceptive use and elected management with a levonorgestrel intrauterine device. A preprocedure exam revealed a plastic foreign body embedded in the posterior vaginal fornix, however, attempted removal in the office was unsuccessful. Subsequent computed tomography imaging of the pelvis revealed a vaginal foreign body, complex adnexal mass, and hydroureter. The patient underwent exam under anesthesia and diagnostic laparoscopy, but required conversion to exploratory laparotomy for removal of a foreign body because of vaginal perforation abutting the rectum. SUMMARY AND CONCLUSION: Foreign bodies not easily removed in the outpatient setting should be considered for surgical removal with consideration of preoperative multidisciplinary coordination when imaging reveals intra-abdominal pathology, such as tubo-ovarian abscess and hydroureter.

Use of Isoquercetin in the Treatment of Prurigo Nodularis.

Atopic dermatitis and prurigo nodularis result from complex interactions between the skin, the immune system, and the external environment. The pruritus associated with these conditions greatly impacts patients' quality of life and lacks uniformly effective treatment. A 57-year-old patient presented with severe atopic dermatitis and subsequent prurigo nodularis refractory to numerous standard therapies. The supplement isoquercetin was initiated and he noted significant, sustained reduction in his pruritus after only four weeks. Isoquercetin is a glycoside derivative with antihistamine properties of quercetin, a natural polyphenol flavonoid found in many plants. It may offer itch relief in patients who have failed more conventional therapies.

J Drugs Dermatol. 2017;16(11):1156-1158.