Karina Kapczuk

Mutations in WNT9B are associated with Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS) is a well‐known malformation pattern of the Müllerian ducts (MDs) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b‐/‐ mice show a MRKHS‐like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs, including 109 patients with MRKHS, as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B. Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6. We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model.

Variations in RBM8A and TBX6 are associated with disorders of the müllerian ducts.

OBJECTIVE To identify genetic causes of malformations of the müllerian ducts. DESIGN Retrospective laboratory study. SETTING University hospital. PATIENT(S) A total of 167 patients with disorders of the müllerian ducts: 116 patients with Mayer-Rokitansky-Küster-Hauser syndrome and 51 patients with fusion disorders of the müllerian ducts. The control group was composed of 94 fertile women with at least one child. INTERVENTION(S) Sequential analysis of RBM8A and TBX6 in a group of 167 clinically well-defined patients with disorders of the müllerian ducts. MAIN OUTCOME MEASURE(S) Identification of rare variants in RBM8A and TBX6. RESULT(S) In total, we detected four RBM8A variants in 13 patients with disorders of the müllerian ducts and two heterozygous TBX6 variants in 5 of 167 patients. CONCLUSION(S) Mutations of RBM8A and TBX6 are associated with disorders of the müllerian ducts.

Nine–month nutritional intervention improves restoration of menses in young female athletes and ballet dancers

BackgroundWe hypothesized that an intervention designed to increase the energy and nutrient intake could serve as an efficacious method to restore normal menstrual functions in athletes and ballet dancers.MethodsIn this study, a 9-month nutritional intervention (NI) was conducted in 21 dancers and 31 athletes with menstrual disorders. Analyses of the body composition were performed, and the levels of LH, FSH, P, E2, TSH, T, PRL, SHBG, leptin, resting metabolic rate (RMR), energy and nutrient intake, total energy expenditure were estimated. The NI was based on an individual diet. The effects of the NI were controlled after 3, 6 and 9 months of use.ResultsThe NI resulted in a significant change of the energy and nutrient intake. After 9 months, a significant increase in the LH level among dancers was observed, while in female athletes this effect was seen after 3 months of the NI use. The 9-month NI resulted in the restoration of regular menses in 3 dancers and 7 athletes, respectively. Women with regular cycles had a higher percentage of the fat mass (FM).ConclusionsA non-pharmacological intervention in female athletes and ballet dancers with menstrual disorders can restore regular menstrual cycles, although restoration of menses may take more than 1 year. An increase in the body fat mass may be one of the most important predictors of restoration of menses.

Testosterone concentrations in female athletes and ballet dancers with menstrual disorders

Abstract Menstrual disorders are common among female athletes and ballet dancers. Endocrine changes, such as high testosterone (HT) levels and high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios, may suggest functional ovarian hyperandrogenism which may induce such dysfunction. The aim of this study was therefore to evaluate endocrine status in female athletes and ballet dancers with menstrual disorders. Their nutritional status and dietary habits were analysed in relation to the testosterone levels. In a cross-sectional approach, 31 female athletes (18.1 ± 2.6 years) and 21 ballerinas (17.1 ± 0.9) with menstrual disorders participated in the study. The levels of serum LH, FSH, progesterone (P), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone, testosterone (T) and sex hormone-binding globulinwere measured to assess hormonal status. In addition, the free androgen index (FAI) was calculated. Nutritional status, total daily energy expenditure and nutritional habits were evaluated. Girls were assigned to one of the following groups: low testosterone (LT) level, normal testosterone level or HT level. There were significant differences between ballerinas and other female athletes in terms of testosterone levels, FAI, age at the beginning of training, length of training period and age at menarche. The PRL level was lowest in the LT group while the FAI index was highest in the HT group. Daily energy and carbohydrate intakes were significantly lower in the HT group. T levels in the study subjects were found to be associated with nutritional factors, energy availability, age at the beginning of training and frequency of training. This is the first report of HT levels being associated with the status of a female ballet dancer, the age of menarche and the length of the training history. Further research is necessary to confirm the results in a larger study group.

Array-CGH Analysis in Patients with Müllerian Fusion Anomalies

Fusion anomalies of the Müllerian ducts are associated with an increased risk for miscarriage and premature labor. In most cases polygenic‐multifactorial inheritance can be assumed but autosomal‐dominant inheritance with reduced penetrance and variable manifestation should be considered. We performed array‐comparative genomic hybridization (CGH) analysis in a cohort of 103 patients with Müllerian fusion anomalies. In 8 patients we detected microdeletions and microduplications in chromosomal regions 17q12, 22q11.21, 9q33.1, 3q26.11 and 7q31.1. The rearrangement in 17q12 including LHX1 and HNF1β as well as in 22q11.21 have already been observed in MRKHS (Mayer‐Rokitansky‐Küster‐Hauser syndrome). In summary, we (1) detected causative micro‐rearrangements in patients with Müllerian fusion anomalies, (2) show that Müllerian fusion anomalies and MRKHS may have a common etiology, and (3) identified new candidate genes for Müllerian fusion anomalies.

Obstructive Müllerian Anomalies in Menstruating Adolescent Girls: A Report of 22 Cases

STUDY OBJECTIVE To assess the clinical course of obstructive Müllerian anomalies found in girls after menarche. DESIGN A retrospective case series of adolescents who, between 2009 and 2016, were treated for vaginal or uterine obstructive malformations diagnosed after menarche. SETTING Division of Gynecology, Poznań University of Medical Sciences, Poznań, Poland. PARTICIPANTS AND INTERVENTIONS Twenty-two patients who, at the age range between 11.4 and 18.2 (median, 13.1) years, between 2 and 74 (median 7.5) months after menarche, underwent surgical repair of obstructive genital anomaly. MAIN OUTCOME MEASURES Müllerian defect type, presentation, radiologic findings, pre- and postoperative course. RESULTS Eighteen patients (18 of 22; 81.8%) were diagnosed with obstructed hemivagina ipsilateral renal anomaly syndrome. One patient (1 of 22; 4.5%) was diagnosed with uterus didelphys and unilateral cervical atresia. Three patients (3 of 22; 13.6%) had unicornuate uterus with a cavitated, noncommunicating rudimentary horn. The right side was affected in 13 patients (13 of 22; 59.1%), and the left side in 9 patients (9 of 22; 40.9%; P > .05). All but 1 patient had renal agenesis on the side of obstruction. Before repair of the obstructive genital anomaly, 4 patients underwent unnecessary surgeries for misdiagnosed ovarian cysts. Serious complications (pelvic inflammatory disease, vesicovaginal fistula) occurred in 2 patients with microperforated pyocolpos. Pelvic endometriosis was found in 4 of our patients. CONCLUSION Our case series suggests that obstructed hemivagina ipsilateral renal anomaly syndrome is the most common obstructive Müllerian anomaly diagnosed in adolescents after menarche. The differential diagnosis for unilateral kidney agenesis accompanied by dysmenorrhea in adolescent girls should include obstructive genital tract anomaly. Accurate diagnosis of an obstructive genital anomaly early after menarche might help prevent unnecessary surgeries and infection-related complications. Meanwhile, prompt surgical correction of an obstructive genital tract anomaly results in relief of symptoms and might reduce the risk of endometriosis.

Congenital malformations and other comorbidities in 125 women with Mayer-Rokitansky-Küster-Hauser syndrome

OBJECTIVE To describe congenital malformations and coexisting disorders occurring in 125 Polish women with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS). The syndrome is defined as uterovaginal aplasia in female with normal 46,XX karyotype. STUDY DESIGN A retrospective analysis of the clinical data of MRKHS patients diagnosed or treated at the Gynecology and Obstetrics Clinical Hospital of Poznan University of Medical Sciences between 2010 and 2015. RESULTS Sixty-eight patients (54,4%) were found to have one or more coexisting anomalies. Thirty-eight patients (55,9% of cases with concomitant malformations, 30,4% of the entire study group) had coexisting anomalies of at least two organ systems. The most frequent extragenital malformations were skeletal anomalies found in 40 patients (32%) and renal anomalies found in 36 patients (28,8%). Fifty-seven patients (45,6%) were diagnosed with typical form (type 1) and 16 (12,8%) with the atypical form (type 2) of MRKHS. In the other 52 patients (41,6%) we diagnosed MURCS association. Five of our patients (4%) had karyotype abnormalities. CONCLUSIONS Our study confirms complexity and clinical heterogeneity of MRKHS. Concomitant congenital malformations are present in about half of MRKHS women. A significant proportion of patients have coexisting anomalies of at least two organ systems. The most common coexisting findings are musculoskeletal and renal abnormalities. Chromosomal aberrations may be present in patients with either typical or atypical form of MRKHS.

[Sexuality of a woman with Mayer-Rokitansky-Küster-Hauser syndrome--case report].

Aplasia or hypoplasia of the uterus and the vagina are pivotal elements of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Psychosexual functioning of women with MRKH syndrome remains to be fully elucidated. Detailed analysis of sexuality of a 31-year-old woman with MRKH syndrome (type MURCS) and with a history of surgical creation of the vagina was performed. Both, biological and psychosocial determinants were investigated in great detail. Genital malformations were found to have significant impact on the sexual identity and sexual behavior of the patient.