Experiences of vaginal lengthening treatment and sexual well-being in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: An interview study.

OBJECTIVE: To explore how women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome experience dilation or surgical vaginal lengthening treatment, and their current sexual well-being. DESIGN: A qualitative interview study. SETTING: Denmark. POPULATION: Women aged ≥25 years diagnosed with MRKH syndrome. METHODS: Semi-structured video interviews were conducted with 18 women. Interviews lasted a median of 92 min and were digitally recorded, transcribed and anonymised. Data were analysed using thematic analysis. MAIN OUTCOME MEASURES: A qualitative analysis of women's experiences. RESULTS: The analysis identified three themes. Firstly, Experiences with dilation treatment revealed dilation as an awkward routine, especially for adolescents living with parents and yet to sexually debut. While some experienced successful vaginal lengthening, others faced treatment failure leading to frustration and self-blame. Secondly, Experiences with neovaginal surgery described the procedure as extremely painful but resulting in a 'normal size' vagina. Some women felt that the procedure had negatively impacted their self-confidence, and all underscored the importance of maturity before opting for surgery. Lastly, Current sex life and sexual well-being indicated a well-functioning sex life for many women, but with reported low sexual confidence and genital self-image due to the perceived 'deviance' of their genitalia. CONCLUSIONS: For women with MRKH syndrome, vaginal lengthening treatment, whether through dilation or surgery, may result in a 'normal size' vagina. However, according to the women's experiences, vaginal lengthening treatment does not adequately foster positive sexual esteem and genital self-image.

Motherhood and attitudes towards motherhood in women with Mayer-Rokitansky-Küster-Hauser syndrome.

OBJECTIVES: The aim of the study was to find out what proportion of women with MRKHS have decided to become mothers and have children or would like to have children and consider various options for motherhood. Additionally, the survey aimed at identifying factors that might influence the women's decisions and opinions regarding adoption, gestational surrogacy (GS) and uterus transplantation (UTx). MATERIAL AND METHODS: The study group consisted of 100 adult women with MRKHS who filled out questionnaires consisting of 56 questions. The survey was self-administered and anonymous. RESULTS: Most of the study participants were under 30, lived in large cities ( > 150 000 inhabitants) and declared to be heterosexuals in a steady relationship (p < 0.05). While 11 participants had children, 66 out of 89 childless women (74%) expressed a desire for motherhood, but as many as 80 surveyed women have felt pressured to have children. The number of participants for whom a biological relationship with offspring was significant and insignificant respectively equaled (p = 1.000). The majority of the study participants supported the process of legalizing GS in Poland (95 vs 4) yet would opt for commercial rather than altruistic GS (64 vs 31) (p < 0.05). Most respondents stated that UTx is consistent with their faith and conscience (91 vs 4) and found UTx ethical (88 vs 4) (p < 0.0001). CONCLUSIONS: The majority of Polish women with MRKHS express the need to become a mother, but only one in ten has a child. The women's interest in biological motherhood is significant.

Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: advancements and implications.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by agenesis/aplasia of the uterus and upper part of the vagina in females with normal external genitalia and a normal female karyotype (46,XX). Patients typically present during adolescence with complaints of primary amenorrhea where the diagnosis is established with significant implications including absolute infertility. Most often cases appear isolated with no family history of MRKH syndrome or related anomalies. However, cumulative reports of familial recurrence suggest genetic factors to be involved. Early candidate gene studies had limited success in their search for genetic causes of MRKH syndrome. More recently, genomic investigations using chromosomal microarray and genome-wide sequencing have been successful in detecting promising genetic variants associated with MRKH syndrome, including 17q12 (LHX1, HNF1B) and 16p11.2 (TBX6) deletions and sequence variations in GREB1L and PAX8, pointing towards a heterogeneous etiology with various genes involved. With uterus transplantation as an emerging fertility treatment in MRKH syndrome and increasing evidence for genetic etiologies, the need for genetic counseling concerning the recurrence risk in offspring will likely increase. This review presents the advancements in MRKH syndrome genetics from early familial occurrences and candidate gene searches to current genomic studies. Moreover, the review provides suggestions for future genetic investigations and discusses potential implications for clinical practice.

Magnetic resonance imaging features of complete androgen insensitivity syndrome in comparison to Mayer-Rokitansky-Küster-Hauser syndrome.

PURPOSE: Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS. METHOD: This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann-Whitney U and Fisher's exact tests. RESULTS: Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values. CONCLUSIONS: MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS.

A Cohort of 469 Mayer-Rokitansky-Küster-Hauser Syndrome Patients-Associated Malformations, Syndromes, and Heterogeneity of the Phenotype.

The Mayer-Rokitansky-Küster-Hauser syndrome is characterized by aplasia of the uterus and upper two-thirds of the vagina. While it can appear as an isolated genital malformation, it is often associated with extragenital abnormalities, with little still known about the pathogenetic background. To provide an overview of associated malformations and syndromes as well as to examine possible ties between the rudimentary tissue and patient characteristics, we analyzed a cohort of 469 patients with MRKHS as well as 298 uterine rudiments removed during surgery. A total of 165 of our patients (35.2%) had associated malformations (MRKHS type II). Renal defects were the most common associated malformation followed by skeletal abnormalities. Several patients had atypical associated malformations or combined syndromes. Uterine rudiments were rarer in patients with associated malformations than in patients without them. Rudiment size ranged from 0.3 cm3 to 184.3 cm3 with a mean value of 7.9 cm3. Importantly, MRKHS subtype or concomitant malformations were associated with a different frequency of uterine tissue as well as a different rudiment size and incidence of endometrial tissue, thereby indicating a clear heterogeneity of the phenotype. Further research into the associated molecular pathways and potential differences between MRKHS subtypes is needed.

Sexual health and sexual well-being of women with Mayer-Rokitansky-Kuester-Hauser syndrome after vaginal reconstruction: a qualitative analysis.

BACKGROUND: Contradictory findings on sexual health in women with Mayer-Rokitansky-Kuester-Hauser syndrome (MRKHS) after vaginal reconstruction point toward the need for more profound assessment of this subject, particularly as it is still unclear what constitutes sexual well-being, especially genital self-image or sexual self-esteem, in women with MRKHS and neovagina. AIM: The aim of this qualitative study was to assess individual sexual health and sexual well-being in the context of MRKHS after vaginal reconstruction, with an emphasis on genital self-image, sexual self-esteem, sexual satisfaction, and coping with MRKHS. METHODS: Qualitative semistructured interviews were conducted with women with MRKHS after vaginal reconstruction (n = 10) with the Wharton-Sheares-George surgical method and a matched control group without MRKHS (n = 20). Women were surveyed about their previous and current sexual activities, perception of and attitudes toward their genitals, disclosure to others, coping with the diagnosis, and perception of surgery. Data were analyzed through qualitative content analysis and compared with the control group. OUTCOMES: The primary outcomes of the study were major categories, such as sexual satisfaction, sexual self-esteem, genital self-image, and dealing with MRKHS, as well as subcategories related to the content analysis. RESULTS: Although half the women in the present study indicated that they were coping well with their condition and were satisfied with sexual intercourse, most felt insecure about their neovagina, were cognitively distracted during intercourse, and showed low levels of sexual self-esteem. CLINICAL IMPLICATIONS: A better understanding of expectations and uncertainties regarding the neovagina might help professionals to support women with MRKHS after vaginal reconstruction to increase sexual well-being. STRENGTHS AND LIMITATIONS: This is the first qualitative study focusing on individual aspects of sexual well-being, especially sexual self-esteem and genital self-image, in women with MRKHS and neovagina. The qualitative study indicates good interrater reliability and data saturation. The limitations of this study include the inherent lack of objectivity resulting from the method but also the fact that all the patients had a particular surgical technique, consequently resulting in limited generalizability of these findings. CONCLUSIONS: Our data indicate that integrating the neovagina into the genital self-image is a prolonged process that is essential for sexual well-being and should thus be the focus of sexual counseling.

Comparison of Sheares vaginoplasty, vaginoplasty using acellular porcine small intestinal submucosa graft and laparoscopic peritoneal vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to compare the perioperative, anatomical and functional outcomes of patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), undergoing Sheares vaginoplasty, vaginoplasty using acellular porcine small intestinal submucosa (SIS) graft or laparoscopic peritoneal (Davydov) vaginoplasty. METHODS: In this retrospective study, a total of 117 patients with MRKHS undergoing creation of a neovagina from 2017 to 2020 were retrospectively investigated. Comparisons between continuous variables were performed using Student's t-test and between qualitative variables using chi-squared tests. RESULTS: The operative time, return of bowel activity and return to work were the longest in the laparoscopic Davydov group (P < 0.001). The total cost was the highest in the SIS graft group (P < 0.001). The length of the neovagina was 7.9 ± 1.2 cm in the Sheares group, 7.1 ± 0.8 cm in the SIS graft group and 8.1 ± 1.1 cm in the laparoscopic Davydov group. The difference in the length of the neovagina was significant (P < 0.001). There was significant difference in the duration of continuous mould wearing (P < 0.001). There were no significant differences in the total female sexual function index (FSFI) scores or in the satisfaction scores of the male partner among the three groups. CONCLUSION: Sheares vaginoplasty and the vaginoplasty using SIS graft caused less trauma and provided similar functional results to laparoscopic peritoneal vaginoplasty. However, the patients in the Sheares group and SIS graft group needed to wear the mould for a longer duration post-surgery. Sheares vaginoplasty can provide a valuable and economic alternative method for the creation of a neovagina in patients with MRKHS.

Mayer-Rokitansky-Kuster-Hauser Syndrome: A rare case report from Nepal.

Introduction: Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKHS) is a rare congenital disorder with an incidence of 1 in 5000 females. It is characterized by uterovaginal aplasia with normal secondary sexual characteristics and genetic karyotype 46XX. The exact etiology of MRKH syndrome is not known. Case presentation: We report a case of type 2 MRKHS with agenesis of left kidney. Discussion: The diagnosis of MRKH mainly depends on imaging study. Transabdominal ultrasonography is the first line investigation but abdomino-pelvic MRI gives more precise and clear information than the prior. So, we suggested our patient to do MRI even though she had done ultrasonography earlier. The differential diagnosis includes congenital vaginal agenesis, low transverse vaginal septum, androgen insensitivity, and imperforate hymen. Conclusion: This case presents that MRKH syndrome can occur with normal endocrine function and secondary sexual characteristics. Surgical correction by creating a neovagina is a good treatment method in young females for sexual intercourse.

First-Line Therapy for Vaginal Atresia. Conservative Treatment vs Surgical Techniques: Quandaries Looking at Numbers.

Although it has been clearly stated that vaginal dilation must be considered the first-line treatment for clinical conditions characterized by an absent or hypoplastic vagina, mainly Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a great number of scientific papers on surgical vaginal reconstructions are reported every year. This wide variety of surgical techniques (more than 10) are recognized and performed worldwide, making it difficult to compare results and define an evidence-based approach. Standardized treatment should be considered even more important in the pediatric and adolescent population for the implications offered by the uterus transplantation scenario.

Psychological correlates of sexual self-esteem in young women with Mayer-Rokitansky-Küster-Hauser syndrome.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a difference (disorder) of sex development that results from Müllerian duct aplasia in 46,XX females. The diagnosis of MRKHS is usually established in late adolescence. The purpose of the study was to assess the impact of congenital absence of uterus and vagina (CAUV) on a patient's psychosexual functioning. PARTICIPANTS AND PROCEDURE: Thirty-two women with MRKHS (mean age 22.9 years) and 32 matched healthy controls (mean age 24.75 years) completed three study questionnaires: the Sexual Self-Esteem Inventory for Women, the Rosenberg Self-Esteem Scale, and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Statistical analysis was performed by IBM SPSS Statistics 22. RESULTS: There was no difference in global self-esteem between the two study groups. MRKHS females had lower sexual self-esteem and experienced higher intensity of some psychological functioning characteristics (paranoia, psychasthenia, schizophrenia) than their peers. Correlations between sexual self-esteem and results on depression, psychopathic deviate, schizophrenia, social introversion and anxiety scales were observed in patients with MRKHS. Global self-esteem and schizophrenia results were significant predictors of sexual self-esteem in the clinical group. Higher global self-esteem and lower results in the schizophrenia scale were associated with higher sexual self-esteem in patients with MRKHS. CONCLUSIONS: Psychological and medical counseling of women with MRKHS should address their impaired sexual self-esteem, especially sexual skills and experiences. While the number of diagnostic responses indicating the presence of specific symptoms in MRKHS females is statistically significantly different, the level of scores obtained does not exceed the threshold of clinical pathology.

Long Term Findings Concerning the Mental and Physical Condition, Quality of Life and Sexuality after Laparoscopically Assisted Creation of a Neovagina (Modified Vecchietti Technique) in Young MRKHS (Mayer-Rokitansky-Küster-Hauser-Syndrome) Patients.

The Mayer-Rokitansky-Küster-Hauser-syndrome (MRKHS) is characterized by a congenital uterine and vaginal aplasia. A large body of literature reports that a diagnosis of MRKHS has a variety of psychological effects on patients and doubts about female identity. The aim of the underlying study was to detect the patient-reported physical and mental health and sexual function before and after laparoscopically assisted creation of a neovagina. 160 women with MRKHS who underwent this type of surgery between September 2009 and December 2015 were invited to complete the questionnaires. Packages consisting of six questionnaires were handed out before surgery, six and 12 months after surgery. Data from 82 patients could be included in the study. Patients had a mean age of 19.9 years at inclusion in the study. We detected an impairment of the health-related mental quality of life. There was no higher risk for psychological disorders. MRKHS patients show similar self-acceptance and normal body image compared to the general population. The sexual function is limited before surgery and normalizes after surgery. Useful factors for coping with the disease are an interdisciplinary approach in diagnostics and treatment, psychosocial adaptation as well as a supportive social environment.

Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a comprehensive update.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics and a normal female karyotype (46,XX). MAIN BODY: The diagnosis is often made during adolescence following investigations for primary amenorrhea and has an estimated prevalence of 1 in 5000 live female births. MRKH syndrome is classified as type I (isolated uterovaginal aplasia) or type II (associated with extragenital manifestations). Extragenital anomalies typically include renal, skeletal, ear, or cardiac malformations. The etiology of MRKH syndrome still remains elusive, however increasing reports of familial clustering point towards genetic causes and the use of various genomic techniques has allowed the identification of promising recurrent genetic abnormalities in some patients. The psychosexual impact of having MRKH syndrome should not be underestimated and the clinical care foremost involves thorough counselling and support in careful dialogue with the patient. Vaginal agenesis therapy is available for mature patients following therapeutical counselling and education with non-invasive vaginal dilations recommended as first-line therapy or by surgery. MRKH syndrome involves absolute uterine factor infertility and until recently, the only option for the patients to achieve biological motherhood was through gestational surrogacy, which is prohibited in most countries. However, the successful clinical trial of uterus transplantation (UTx) by a Swedish team followed by the first live-birth in September, 2014 in Gothenburg, proofed the first available fertility treatment in MRKH syndrome and UTx is now being performed in other countries around the world allowing women with MRKH syndrome to carry their own child and achieve biological motherhood. CONCLUSION: Several advances in research across multiple disciplines have been made in the recent years and this kaleidoscopic review provides a current status of various key aspects in MRKH syndrome and provides perspectives for future research and improved clinical care.

Rare genital malformations in women's health research: sociodemographic, regional, and disease-related characteristics of patients with Mayer-Rokitansky-Küster-Hauser syndrome.

BACKGROUND: The Mayer-Rokitansky-Küster-Hauser syndrome, MRKHS, is a rare (orphan) disease characterized by the aplasia or hypoplasia of the uterus and the vagina. In women's health research, little is known as to how much care provision for patients with MRKHS takes into account their socio-demographic together with their clinical characteristics. This work examines the patients' socio-demographic characteristics, highlighting issues of inappropriate and deficient provision of care. METHODS: The study was carried out as part of the larger TransCareO project and included a group of N=129 MRKHS patients who underwent surgery between 2008 and 2012. Using a specially developed questionnaire, we analyzed MRKHS patients' data found both in the clinical documentation of the Department for Women's Health, University Hospital of Tübingen and the patient surveys of the Center for Rare Genital Malformations (CRGM/ ZSGF). Patients who took part in interviews were compared with non-respondents. RESULTS: Patient respondents and non-respondents did not differ as to the parameters of interest. In most cases, primary amenorrhea was reported as an admission reason. In 24% of patients, a medical intervention (hymenal incision or hormone treatment) already occurred before admission to the Center in Tübingen and proper diagnosis of MRKHS. About one third received in advance inappropriate treatment. During the therapy, more than half of the patients were in a solid partnership. 10% of the family anamneses documented the occurrence of urogenital malformations. CONCLUSIONS: Care provision for MRKHS patients is largely characterized by delayed proper diagnosis and in part, by inappropriate treatment attempts; there are also indications of regional differences. Anamnestic clues such as an asymptomatic amenorrhea or renal abnormalities of unclear origin still fail to result early enough in referral to a center on the basis of suspected MRKHS diagnosis. Urogenital malformations in the family are more common in patients than in the general population. For patients, a wide range of burdens are associated with the diagnosis. Abnormalities compared to their female peers occur, for instance, in the partnership status: MRKHS patients have more rarely a partner.

Sexual Experience before Treatment for Vaginal Agenesis: A Retrospective Review of 137 Women.

STUDY OBJECTIVE: To summarize the self-reported sexual experiences of women with vaginal agenesis before treatment and discuss the clinical implications. DESIGN: A retrospective review of pretreatment baseline sexuality data and medical records of women with vaginal agenesis seeking vaginal construction. SETTING: A specialist multidisciplinary center for women with genital differences associated with diverse sex development. PARTICIPANTS: One hundred thirty-seven women with untreated vaginal agenesis associated with Mayer-Rokitansky-Küster-Hauser Syndrome and complete androgen insensitivity syndrome aged 15 to 41 years (mean age, 20 years). INTERVENTIONS: Gynecological examination and completion of questionnaires. MAIN OUTCOME MEASURES: (1) Sexual Experiences Questionnaire; (2) Multidimensional Sexuality Questionnaire; (3) Vaginal Self-Perceptions; and (4) vaginal length. RESULTS: A sizable proportion of women reported having had sexually intimate experiences before any medical intervention on the vagina. Vaginal length, which ranged from dimple to 7 cm and averaged 2.7 cm for the cohort, was unrelated to the range of sexual experiences. Most women perceived their vagina as being too small, but less than half believed that a sexual partner would notice this. Two-thirds of the cohort subsequently completed the dilation program, which was not predicted by pretreatment vaginal length or sexual experience. CONCLUSION: Contrary to the assumption that a vagina of certain dimensions is a prerequisite for women to "have sex," many women with Mayer-Rokitansky-Küster-Hauser syndrome and complete androgen insensitivity syndrome reported having experienced genital and nongenital sexual activities with no medical interventions. It is recommended that treatment providers affirm women's capacity for sexual intimacy, relationships, and enjoyment before they introduce the topic of vaginal construction as a non-urgent choice.

Array-comparative genomic hybridization 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 HNF1ß 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.

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.