21 results on '"46, XX Disorders of Sex Development epidemiology"'
Search Results
2. Prevalence of urinary, prolapse, and bowel symptoms in Mayer-Rokitansky-Küster-Hauser syndrome.
- Author
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Pennesi CM, English EM, Bell S, Lossie AC, Quint EH, and Swenson CW
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- Adult, Constipation epidemiology, Cross-Sectional Studies, Female, Gynecologic Surgical Procedures methods, Humans, Mullerian Ducts surgery, Quality of Life, Surveys and Questionnaires, Urinary Tract Infections epidemiology, Urination Disorders epidemiology, Vagina surgery, 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development surgery, Congenital Abnormalities epidemiology, Congenital Abnormalities surgery, Fecal Incontinence epidemiology, Mullerian Ducts abnormalities, Pelvic Floor Disorders epidemiology, Pelvic Organ Prolapse epidemiology, Urologic Diseases epidemiology
- Abstract
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., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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3. Clinical Characteristics of 46,XX Males with Congenital Adrenal Hyperplasia
- Author
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Savaş-Erdeve Ş, Aycan Z, Çetinkaya S, Öztürk AP, Baş F, Poyrazoğlu Ş, Darendeliler F, Özsu E, Şıklar Z, Demiral M, Unal E, Özbek MN, Gürbüz F, Yüksel B, Evliyaoğlu O, Akyürek N, and Berberoğlu M
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Educational Status, Female, Follow-Up Studies, Hormone Replacement Therapy, Humans, Infant, Male, Retrospective Studies, Sex Reassignment Surgery, Young Adult, 46, XX Disorders of Sex Development diagnosis, 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development therapy, Adrenal Hyperplasia, Congenital diagnosis, Adrenal Hyperplasia, Congenital epidemiology, Adrenal Hyperplasia, Congenital therapy, Virilism diagnosis, Virilism epidemiology, Virilism therapy
- Abstract
Objective: To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male., Methods: A national database was created. The data of patients were asked to be recorded in the data form., Results: The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%., Conclusion: It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage.
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- 2021
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4. Perspectives of 281 patients with Mayer-Rokitansky-Küster-Hauser Syndrome on uterine transplantation.
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Fischer N, Xun H, Lossie A, Fadavi D, Darrach H, Yesantharao P, Kraenzlin F, Singh B, Sacks JM, and Segars JH
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- 46, XX Disorders of Sex Development epidemiology, Adolescent, Adult, Congenital Abnormalities epidemiology, Cross-Sectional Studies, Female, Humans, Infertility, Female epidemiology, Mullerian Ducts surgery, Surveys and Questionnaires, Young Adult, 46, XX Disorders of Sex Development psychology, 46, XX Disorders of Sex Development surgery, Congenital Abnormalities psychology, Congenital Abnormalities surgery, Infertility, Female psychology, Infertility, Female surgery, Mullerian Ducts abnormalities, Organ Transplantation psychology, Uterus transplantation
- Abstract
Objectives: To investigate the personal, ethical, and financial perspectives of individuals with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), a congenital uterine factor infertility condition, regarding uterine transplantation (UTx)., Design: Cross-sectional, quantitative survey., Setting: A 60-item anonymous electronic questionnaire was disseminated via social media sites., Patients: International members of the Beautiful You MRKH Foundation., Interventions: None., Main Outcome Measures: The survey contained UTx educational materials followed by questions assessing participants' baseline knowledge, global perceptions, financial concerns, and ethical considerations regarding UTx., Results: We received 281 responses, with a mean participant age of 28.2 ± 9.8 years. After reviewing the education material, most participants considered receiving a UTx (73%), believed that it should be an option for all women with uterine factor infertility (86%), and believed that it should be covered by health insurance (78%). Respondents perceived the benefits of the procedure to outweigh the risks (67%) and considered it to be an ethical procedure (82%). Almost one-half (49%) were willing to spend more than $10,000 out of pocket to receive the procedure. When asked to rank the risk of UTx to self, donor, and fetus in order of personal importance, 21% ranked their own safety last., Conclusion: There is a profound desire in the MRKH community for UTx to become more widely available and affordable. MRKH patients may represent a vulnerable population requiring special considerations for informed consent and rigorous evaluation for UTx. Providers caring for MRKH patients should be prepared to provide education about UTx and to thoughtfully engage with news and media outlets to communicate evidence-supported information., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2021
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5. Neovagina Creation: A Novel Improved Laparoscopic Vecchietti Procedure in Patients with Mayer-Rokitansky-Küster-Hauster Syndrome.
- Author
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Wang YY, Duan H, Zhang XN, and Wang S
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- 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development pathology, Adolescent, Adult, Case-Control Studies, China epidemiology, Congenital Abnormalities epidemiology, Congenital Abnormalities pathology, Female, Humans, Inventions, Mullerian Ducts pathology, Mullerian Ducts surgery, Postoperative Complications epidemiology, Retrospective Studies, Self Concept, Sexual Dysfunction, Physiological epidemiology, Sexual Dysfunction, Physiological etiology, Therapies, Investigational methods, Treatment Outcome, Vagina abnormalities, Vagina pathology, Young Adult, 46, XX Disorders of Sex Development surgery, Congenital Abnormalities surgery, Gynecologic Surgical Procedures methods, Laparoscopy methods, Mullerian Ducts abnormalities, Plastic Surgery Procedures methods, Surgically-Created Structures pathology, Vagina surgery
- Abstract
Study Objective: To report a new improved laparoscopic Vecchietti vaginoplasty in patients with congenital vaginal agenesis and to investigate its efficacy and safety., Design: A retrospective descriptive and case-control study., Setting: Single academic institution., Patients: Women who were diagnosed with Mayer-Rokitansky-Küster-Hauster (MRKH) syndrome and underwent our new improved laparoscopic Vecchietti procedure from July 2010 to June 2019 were selected as the study group. The eligible participants had congenital vaginal agenesis with normal 46,XX karyotype and ovarian function. Age-matched, nulliparous, sexually active women were selected as the control group., Interventions: Women with MRKH syndrome in the study group underwent the novel improved laparoscopic Vecchietti procedure. All participants in both groups were required to complete Female Sexual Function Index and Female Genital Self-Image Scale questionnaires., Measurements and Main Results: The effects of our procedure, including the anatomic and functional efficacy of the neovagina, were the primary outcomes. The secondary outcomes consisted of the perioperative complications, surgical morbidities, and long-term postoperative discomfort. A total of 79 patients with MRKH syndrome underwent our new improved Vecchietti vaginoplasty, of whom 44 (55.7%) were diagnosed as Type I MRKH syndrome, whereas 35 (44.3%) were Type II MRKH syndrome. At a 30-month follow-up after surgery, an anatomic neovagina measuring 10.44 cm in length and 1.30 cm in width was achieved. All 79 patients obtained anatomic success with 92.41% of functional efficacy. Compared with 81 age-matched, nulliparous women in the control group, there was no statistical difference regardless of individual measure or total Female Sexual Function Index scores (p >.05). The Female Genital Self-Image Scale assessment showed a significantly lower score in patients undergoing the vaginoplasty (20.14 ± 3.05 vs 22.95 ± 2.12; p <.001). There were no severe perioperative complications except 1 mild bladder injury and 1 transient fever., Conclusion: Our novel improved laparoscopic Vecchietti vaginoplasty is a relatively safe and effective method for surgical treatment of congenital vaginal agenesis. It may be an alternative to neovagina creation for reaching satisfying anatomic and functional efficacy and improving patients' sexual function., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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6. Pelvic pain in patients with complex mullerian anomalies including Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH), obstructed hemi-vagina ipsilateral renal anomaly (OHVIRA), and complex cloaca.
- Author
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Schall K, Parks M, Nemivant S, Hernandez J, and Weidler EM
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- Adolescent, Arizona epidemiology, Chronic Pain epidemiology, Chronic Pain etiology, Depression etiology, Female, Humans, Pelvic Pain epidemiology, Retrospective Studies, Young Adult, 46, XX Disorders of Sex Development epidemiology, Cloaca abnormalities, Congenital Abnormalities epidemiology, Kidney abnormalities, Mullerian Ducts abnormalities, Pelvic Pain etiology, Vagina abnormalities
- Abstract
Caring for patients with congenital pelvic anomalies can be challenging in many ways but one crucial aspect is providing longitudinal into adulthood. Newborns with urinary, intestinal or vaginal obstruction require urgent operations to relieve obstruction followed by multiple reconstructive procedures involving the perineum. Openings are created in the pelvic floor musculature that did not exist in development. Adolescence presents further challenges for these postoperative patients while other diagnoses present for the first time in the peri-pubertal teenage years. Young adults can have new symptoms when they become sexually active and are faced with reproductive decisions. During all of these time periods, optimization of function is of paramount importance and patients who are suffering are not able to participate in school, sports or work. This study evaluates the prevalence of pelvic pain in newborns and adolescents with complex congenital pelvic anomalies, associated factors and possible treatment options., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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7. Spectrum of Type I and Type II Syndromes and Associated Malformations in Chinese Patients with Mayer-Rokitansky-Küster-Hauser Syndrome: A Retrospective Analysis of 274 Cases.
- Author
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Deng S, He Y, Chen N, and Zhu L
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- 46, XX Disorders of Sex Development classification, Abnormalities, Multiple, Adult, China epidemiology, Cohort Studies, Congenital Abnormalities classification, Cross-Sectional Studies, Female, Humans, Kidney abnormalities, Retrospective Studies, Syndrome, 46, XX Disorders of Sex Development epidemiology, Congenital Abnormalities epidemiology, Mullerian Ducts abnormalities
- Abstract
Study Objective: To analyze the spectrum of type I and type II malformations in Chinese patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a cross-sectional descriptive study that used data from a National Clinical Research Center for Obstetrical and Gynecological Diseases of China, reviewed from January 2009 to July 2017. Data of in- and outpatients with MRKH syndrome were reviewed and analyzed., Results: A total of 274 cases were included in the analysis: 197/274 (71.9%) with type I MRKH syndrome and the remaining 77/274 (28.1%) with type II MRKH syndrome. The rate of concurrent deformities was 32/244 (13.1%) for renal malformation, and 49/125 (39.2%) for skeletal malformation. Nine patients had renal and skeletal malformations (Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia). Cardiac, neurologic, and other malformations (eg, anal atresia) were sporadic. The percentage of type II MRKH syndrome in our cohort was considerably higher than that reported 43/594 (7.2%) in a previous large-scale study in southern China, but lower than that 489/1259 (46.2%) reported for Caucasian individuals., Conclusion: The spectrum of type I and type II MRKH syndrome varies across different races and geological locations., (Copyright © 2019. Published by Elsevier Inc.)
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- 2019
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8. Treatment of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome in Denmark: a nationwide comparative study of anatomical outcome and complications.
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Herlin M, Bay Bjørn AM, Jørgensen LK, Trolle B, and Petersen MB
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- 46, XX Disorders of Sex Development diagnostic imaging, Adolescent, Cohort Studies, Congenital Abnormalities diagnostic imaging, Denmark epidemiology, Dilatation adverse effects, Dilatation methods, Female, Follow-Up Studies, Humans, Mullerian Ducts diagnostic imaging, Postoperative Complications diagnosis, Prospective Studies, Registries, Treatment Outcome, Vagina diagnostic imaging, Young Adult, 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development therapy, Congenital Abnormalities epidemiology, Congenital Abnormalities therapy, Mullerian Ducts abnormalities, Postoperative Complications epidemiology, Vagina abnormalities
- Abstract
Objective: To compare the long-term anatomical outcome and complications in treatments of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome., Design: A historical comparative follow-up study using medical chart reviews., Setting: Public hospitals., Patient(s): A nationwide cohort of patients diagnosed with MRKH syndrome (n = 168)., Intervention(s): McIndoe vaginoplasty (n = 54), self-dilation (n = 60), coital dilation (n = 20), Baldwin vaginoplasty (n = 4), Williams vaginoplasty (n = 3), Davydov vaginoplasty (n = 2), or no treatment (n = 29)., Main Outcome Measures(s): Mean vaginal depth at follow-up, anatomical treatment success rates at levels of ≥6 cm, ≥7 cm, and ≥8 cm, complications, and resurgery., Result(s): Mean vaginal depths were 7.4 cm (95% confidence interval [CI] 6.8-8.1 cm), 7.3 cm (95% CI 6.7-7.9 cm), and 8.7 cm (95% CI 7.9-9.5 cm) at follow-up in patients treated by McIndoe vaginoplasty, self-dilation, and coital dilation, respectively. Overall complication rates in the three groups were 35/54 (65%), 21/52 (35%), and 1/20 (5%), respectively. Eighteen (33%) of the patients who underwent McIndoe vaginoplasty needed resurgery., Conclusion(s): Our findings support the current recommendations of dilation therapy as the first-line treatment of vaginal agenesis and emphasize the relevance of coital dilation in patients able to regularly engage in coital activity. However, further studies of functional outcome and patient satisfaction are needed., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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9. Incidence, prevalence, diagnostic delay, morbidity, mortality and socioeconomic status in males with 46,XX disorders of sex development: a nationwide study.
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Berglund A, Johannsen TH, Stochholm K, Aksglaede L, Fedder J, Viuff MH, Main KM, and Gravholt CH
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- 46, XX Disorders of Sex Development diagnosis, 46, XX Disorders of Sex Development mortality, Adolescent, Adult, Child, Child, Preschool, Delayed Diagnosis, Denmark epidemiology, Health Status, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Prevalence, Social Class, Socioeconomic Factors, Young Adult, 46, XX Disorders of Sex Development epidemiology
- Abstract
Study Question: What is the epidemiology and trajectory of health and socioeconomic status in males with 46,XX disorders of sex development (DSD)?, Summary Answer: 46,XX DSD males had an increased overall morbidity compared to male background population controls, and the socioeconomic status was inferior on outcome parameters such as education and long-term income., What Is Known Already: 46,XX DSD males are rare and estimates of prevalence and incidence are limited. An increased morbidity and mortality as well as a negatively affected socioeconomic status are described in males with Klinefelter Syndrome. However, this has never been systematically studied in 46,XX DSD males., Study Design, Size, Duration: In this nationwide registry study including 44 males with a verified diagnosis of 46,XX DSD we aimed to estimate incidence, prevalence and diagnostic delay. Further, we aimed to study morbidity, mortality and socioeconomic outcome parameters using the Danish registries. The socioeconomic outcome parameters were education, income, retirement, parenthood and cohabitation. 46,XX DSD males were born during 1908-2012 and follow-up started at birth or at start of registration and ended in 2014., Participants/materials, Setting, Methods: Potential cases (n = 69) were identified in the Danish Cytogenetic Central Registry and the diagnosis was verified by medical record evaluation (n = 44). A randomly selected age-matched control group of 100 males and 100 females per case was identified by Statistics Denmark., Main Results and the Role of Chance: Among newborn males the prevalence of diagnosed 46,XX DSD males was 3.5-4.7 per 100 000. Median age at diagnosis was 17.0 years (range: 0.0-62.8). Overall morbidity was increased compared to male controls (hazard ratio [HR] = 2.4, 95% CI: 1.8-3.3) but not when excluding endocrine and urogenital diseases as well as congenital malformations (HR = 1.2, 95% CI: 0.8-1.6). Mortality was not increased (HR = 0.6, 95% CI: 0.2-2.5) compared to male controls. 46,XX DSD males had poorer education (HR = 0.1, 95% CI: 0.0-0.9) and fewer fatherhoods (HR = 0.4, 95% CI: 0.2-0.7) than male controls, and their income was reduced for the following age groups; 45-49 years: odds ratio [OR] = 0.4 (95% CI: 0.2-0.7); 50-54 years: OR = 0.1 (95% CI: 0.0-0.6)., Limitations, Reasons for Caution: The study cohort is rather small, although it is large in comparison to other studies on 46,XX DSD males. Some 46,XX DSD males may have been excluded from the study owing to lack of data in medical records, making the diagnosis impossible to verify. As in all epidemiologic studies a risk of misclassification must be considered when interpreting the study results, and as the study included diagnosed 46,XX DSD males only, conclusions cannot be extended to non-diagnosed 46,XX DSD males., Wider Implications of the Findings: This study provides a new insight into trajectory of health and socioeconomic status of 46,XX DSD males., Study Funding/competing Interest(s): This study was funded by research grants from the Health Research Fund of Central Denmark Region, the A.P. Møller Foundation 'Fonden til Laegevidenskabens Fremme', the Lundbeck Foundation and the Novo Nordisk Foundation (NNF13OC0003234 and NNF15OC0016474). The authors have nothing to declare., Trial Registration Number: N/A., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)
- Published
- 2017
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10. Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families.
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Williams LS, Demir Eksi D, Shen Y, Lossie AC, Chorich LP, Sullivan ME, Phillips JA 3rd, Erman M, Kim HG, Alper OM, and Layman LC
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- Adult, Cohort Studies, Family, Genetic Markers genetics, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Humans, Internationality, Prevalence, Risk Factors, Young Adult, 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development genetics, Congenital Abnormalities epidemiology, Congenital Abnormalities genetics, Hepatocyte Nuclear Factor 1-beta genetics, LIM-Homeodomain Proteins genetics, Mullerian Ducts abnormalities, Polymorphism, Single Nucleotide genetics, Transcription Factors genetics, Wnt4 Protein genetics
- Abstract
Objective: To study the genetic cause of Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). Although a few candidate genes and genomic domains for have been reported for MRKH, the genetic underpinnings remain largely unknown. Some of the top candidate genes are WNT4, HNF1B, and LHX1. The goals of this study were to: 1) determine the prevalence of WNT4, HNF1B, and LHX1 point mutations, as well as new copy number variants (CNVs) in people with MRKH; and 2) identify and characterize MRKH cohorts., Design: Laboratory- and community-based study., Setting: Academic medical centers., Patient(s): A total of 147 MRKH probands and available family members., Interventions(s): DNA sequencing of WNT4, HNF1B, and LHX1 in 100 MRKH patients, chromosomal microarray analysis in 31 North American MRKH patients, and characterization and sample collection of 147 North American and Turkish MRKH probands and their families., Main Outcome Measure(s): DNA sequence variants and CNVs; pedigree structural analysis., Result(s): We report finding CNVs in 6/31 people (∼19%) with MRKH, but no point mutations or small indels in WNT4, HNF1B, or LHX1 in 100 MRKH patients. Our MRKH families included 43 quads, 26 trios, and 30 duos. Of our MRKH probands, 87/147 (59%) had MRKH type 1 and 60/147 (41%) had type 2 with additional anomalies., Conclusion(s): Although the prevalence of WNT4, HNF1B, and LHX1 point mutations is low in people with MRKH, the prevalence of CNVs was ∼19%. Further analysis of our large familial cohort of patients will facilitate gene discovery to better understand the complex etiology of MRKH., (Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.)
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- 2017
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11. The Spectrum of Ovotesticular Disorders of Sex Development in South Africa: A Single-Centre Experience.
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Ganie Y, Aldous C, Balakrishna Y, and Wiersma R
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- Child, Child, Preschool, Female, Humans, Infant, Male, South Africa epidemiology, South Africa ethnology, 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development ethnology, 46, XX Disorders of Sex Development genetics, 46, XX Disorders of Sex Development pathology, Black People ethnology, Black People genetics, Disorder of Sex Development, 46,XY epidemiology, Disorder of Sex Development, 46,XY ethnology, Disorder of Sex Development, 46,XY genetics, Disorder of Sex Development, 46,XY pathology, Ovotesticular Disorders of Sex Development epidemiology, Ovotesticular Disorders of Sex Development ethnology, Ovotesticular Disorders of Sex Development genetics, Ovotesticular Disorders of Sex Development pathology
- Abstract
Objective: To describe the clinical characteristics, biochemistry, histopathology, and long-term outcomes in subjects with ovotesticular (OT) disorder of sex development (DSD)., Study Design: This is a retrospective subset analysis of 64 cases of histologically confirmed OT DSD., Results: All subjects were South African; 97% (n = 62) were African and 92% (n = 59) were of Zulu ethnicity. The most common karyotype was 46,XX (88%; n = 56), followed by 46,XY (8%), 46,XY/45,X (3%), and 46,XX/46,XY (1%). The median age at presentation was 7 months (0.5 months to 5.1 years). Sixty-one of the subjects (95%) presented with DSD. The ovotestis was the most frequent gonad (56%), followed by the ovary (23%) and the testis (16%). Testes were more commonly located on the right and ovaries on the left (p < 0.0001). The male gender was the predominant sex of rearing in two-thirds of the subjects. Gender dysphoria was noted in 8 subjects (11%) at a median of 6.4 (4.3-9.3) years. Long-term follow-up (n = 14) revealed spontaneous puberty in 5 subjects, gender dysphoria in 2 subjects, and neuropsychiatric disorders in 4 subjects., Conclusion: OT DSD is an important differential diagnosis in Black South Africans with 46,XX DSD., (© 2017 S. Karger AG, Basel.)
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- 2017
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12. Congenital malformations and other comorbidities in 125 women with Mayer-Rokitansky-Küster-Hauser syndrome.
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Kapczuk K, Iwaniec K, Friebe Z, and Kędzia W
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- 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development genetics, Abnormal Karyotype, Abnormalities, Multiple epidemiology, Abnormalities, Multiple genetics, Adolescent, Adult, Bone and Bones abnormalities, Cohort Studies, Comorbidity, Congenital Abnormalities epidemiology, Congenital Abnormalities genetics, Female, Hernia, Inguinal epidemiology, Hospitals, University, Humans, Incidence, Kidney abnormalities, Medical Records, Middle Aged, Mullerian Ducts physiopathology, Outpatient Clinics, Hospital, Poland epidemiology, Prevalence, Retrospective Studies, Urinary Tract abnormalities, Young Adult, 46, XX Disorders of Sex Development physiopathology, Abnormalities, Multiple physiopathology, Congenital Abnormalities physiopathology, Mullerian Ducts abnormalities
- Abstract
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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
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- 2016
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13. Prevalence and patient characteristics of Mayer-Rokitansky-Küster-Hauser syndrome: a nationwide registry-based study.
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Herlin M, Bjørn AM, Rasmussen M, Trolle B, and Petersen MB
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- 46, XX Disorders of Sex Development diagnosis, Adolescent, Congenital Abnormalities diagnosis, Cross-Sectional Studies, Denmark epidemiology, Female, Humans, Prevalence, Registries, Retrospective Studies, Symptom Assessment, Young Adult, 46, XX Disorders of Sex Development epidemiology, Congenital Abnormalities epidemiology, Mullerian Ducts abnormalities
- Abstract
Study Question: What is the prevalence of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome?, Summary Answer: The prevalence of MRKH syndrome in Denmark is 1 in 4982 (95% confidence interval (CI): 4216-5887) live female births., What Is Known Already: The prevalence of MRKH syndrome has been estimated to be around 1 in 4000-5000 females. However, population-based prevalence studies of MRKH syndrome are sparse. Moreover, population-based data on patient characteristics are lacking., Study Design, Size, Duration: This retrospective cohort study used the Danish National Patient Registry (DNPR) to identify a nationwide population-based cohort of patients with MRKH syndrome. Subsequently, patients were linked to the Danish Cytogenetic Central Registry (DCCR) and patient medical records in order to validate the diagnoses., Participants/materials, Setting, Methods: Hospitalizations and outpatient visits from 1994 to April 2015 at all public hospitals in Denmark were searched for patients assigned with a diagnosis code indicative of MRKH syndrome. The diagnoses were validated by diagnostic history in the DNPR and DCCR data, and by review of patient medical records. The prevalence was estimated considering the identified patients born from 1974 to 1996. Patient characteristics were described using data collected from DNPR, DCCR and patient medical records., Main Results and the Role of Chance: The diagnosis was validated in 304 of 314 patients (96.8%) suspected with MRKH syndrome by review of diagnostic histories, DCCR data, and medical records and in 168 patients, the diagnosis of MRKH syndrome was confirmed (positive predictive value = 55.3% (95% CI: 49.5-60.9%)). The prevalence was 1 in 4982 (95% CI: 4216-5887) live female births based on 138 patients born from 1974 to 1996. Typical MRKH syndrome and atypical MRKH syndrome/Müllerian duct aplasia, Renal aplasia, and Cervicothoracic Somite dysplasia association were present in 56.5% and 43.5% of the patients, respectively. Kidney malformations were the most prevalent extragenital malformations, described in 38 of 111 patients (34.2%). However, in 57 patients (33.9%) no urinary tract imaging was performed. Three familial cases of MRKH syndrome were identified., Limitations, Reasons for Caution: We identified all patients with MRKH syndrome diagnosed at public hospitals in Denmark. When interpreting the prevalence estimate, caution must be taken due to limitations such as patients not diagnosed in public hospitals, other diagnosis codes not used in the study and the unknown impact of a net positive migration rate in Denmark., Wider Implications of the Findings: The prevalence estimate around 1 in 5000 is in accordance with a previous nationwide study. We consider the prevalence generalizable to other Caucasian populations. Prevalence studies of non-Caucasian populations are needed to investigate whether inter-ethnic differences in prevalence exist. Finally, the results of this study emphasize the need for sufficient basic examinations of patients with MRKH syndrome, including the importance of family medical history., Study Funding/competing Interests: None., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2016
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14. The reproductive potential of patients with Mayer-Rokitansky-Küster-Hauser syndrome using gestational surrogacy: a systematic review.
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Friedler S, Grin L, Liberti G, Saar-Ryss B, Rabinson Y, and Meltzer S
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- 46, XX Disorders of Sex Development complications, 46, XX Disorders of Sex Development epidemiology, Congenital Abnormalities epidemiology, Female, Humans, Infertility, Female epidemiology, Infertility, Female etiology, Pregnancy, Pregnancy Outcome epidemiology, Pregnancy Rate, Treatment Outcome, 46, XX Disorders of Sex Development therapy, Congenital Abnormalities therapy, Infertility, Female therapy, Mullerian Ducts abnormalities, Surrogate Mothers
- Abstract
Women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome may reproduce after uterine transplantation or IVF using a gestational surrogate. As uterine transplantation is still an experimental procedure, data on their clinical outcome using assisted reproduction techniques are imperative to allow evidence-based counselling. For this purpose, a systematic non-restricted electronic literature search was conducted. The 14 studies included in this review were published between 1988 and 2011. From a cohort of 140 patients with MRKH syndrome, mostly from the the USA and Israel, only four studies contained data on more than 10 patients; the others were case reports or small series. In the studies reviewed, 125 patients underwent 369 cycles of IVF with gestational surrogacy, and delivered 71 newborns. The reporting of outcome of patients with MRKH syndrome undergoing assisted reproduction techniques in the available literature is less than optimal and is characterized by bias of publication, inconsistent reports, including few patients, treated over a long time span, and lacking systematic reports from large IVF centres. None of the national registries contain specific outcome data on patients with MRKH syndrome. The paucity of data limits the possibility to draw firm conclusions but substantiates the need for a systematic multicentre reporting system., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)
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- 2016
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15. DNA copy number variations are important in the complex genetic architecture of müllerian disorders.
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McGowan R, Tydeman G, Shapiro D, Craig T, Morrison N, Logan S, Balen AH, Ahmed SF, Deeny M, Tolmie J, and Tobias ES
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- 46, XX Disorders of Sex Development epidemiology, Abnormalities, Multiple epidemiology, Adolescent, Adult, Comparative Genomic Hybridization, Congenital Abnormalities epidemiology, Cytogenetic Analysis, Disorders of Sex Development epidemiology, Female, Humans, Young Adult, 46, XX Disorders of Sex Development genetics, Abnormalities, Multiple genetics, Congenital Abnormalities genetics, DNA Copy Number Variations, Disorders of Sex Development genetics, Mullerian Ducts abnormalities
- Abstract
Objective: To clinically and genetically investigate women with müllerian disorders, including Mayer-Rokitanksy-Kuster-Hauser (MRKH) syndrome., Design: Two-year prospective clinical and laboratory study., Setting: Not applicable., Patient(s): Thirty-five women over 16 years of age with a müllerian disorder, including MRKH., Intervention(s): Women were recruited from specialist gynecology clinics or identified from the Scottish Disorders of Sex Development Register (www.sdsd.scot.nhs.uk/index.html). Associated abnormalities were detected by clinical examination, imaging studies, and biochemical analyses. Chromosomal microduplications and microdeletions were detected by array comparative genomic hybridization (CGH) and validated by fluorescence in situ hydridization., Main Outcome Measure(s): Identification of associated congenital and biochemical abnormalities and identification of regions of genomic imbalance using array CGH., Result(s): Associated congenital anomalies were common, present in 25/35 (71%) of affected women, particularly renal and skeletal abnormalities, which were present in 15/35 (43%) and 17/35 (49%) women, respectively. Using array CGH, novel or recurrent regions of genomic imbalance were identified in 4/11 (36%) women with MRKH and in 5/24 (21%) women with other müllerian abnormalities., Conclusion(s): Additional congenital abnormalities and regions of genomic imbalance are common in women with müllerian disorders, including MRKH. Recurrent microdeletions and microduplications associated with MRKH implicate specific possibly causative genes. The investigation of women with müllerian disorders should be thorough, and array CGH should be considered, given the potential highly significant familial implications of a chromosomal abnormality., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2015
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16. Quality of life of patients with 46,XX and 46,XY disorders of sex development.
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Amaral RC, Inacio M, Brito VN, Bachega TA, Domenice S, Arnhold IJ, Madureira G, Gomes L, Costa EM, and Mendonca BB
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- Adrenal Hyperplasia, Congenital epidemiology, Adrenal Hyperplasia, Congenital physiopathology, Adrenal Hyperplasia, Congenital psychology, Adult, Disorders of Sex Development epidemiology, Disorders of Sex Development physiopathology, Disorders of Sex Development psychology, Female, Humans, Male, 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development physiopathology, 46, XX Disorders of Sex Development psychology, Disorder of Sex Development, 46,XY epidemiology, Disorder of Sex Development, 46,XY physiopathology, Disorder of Sex Development, 46,XY psychology, Quality of Life
- Abstract
Disorders of sex development (DSD) result from abnormalities in the complex process of sex determination and differentiation. An important consideration to guide the assignment of social sex in newborns with ambiguous genitalia is the quality of life (QoL) of these patients in adulthood. The rarity of most DSD conditions makes it difficult to conduct a long-term follow-up of affected patients through adulthood. This review of papers on the QoL of DSD patients evaluated in developing and developed countries by qualitative and quantitative instruments revealed a large spectrum of QoL, ranging from very poor to similar to, or even better than, the normal population. A more adequate QoL was found in patients from tertiary centres, indicating that the medical care of DSD patients should be multidisciplinary and carried out by specialized teams., (© 2014 John Wiley & Sons Ltd.)
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- 2015
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17. Quality of life in a large cohort of adult Brazilian patients with 46,XX and 46,XY disorders of sex development from a single tertiary centre.
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Cassia Amaral R, Inacio M, Brito VN, Bachega TA, Oliveira AA Jr, Domenice S, Denes FT, Sircili MH, Arnhold IJ, Madureira G, Gomes L, Costa EM, and Mendonca BB
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- 46, XX Disorders of Sex Development psychology, Adolescent, Adult, Brazil epidemiology, Disorder of Sex Development, 46,XY psychology, Female, Humans, Male, Middle Aged, Social Adjustment, Social Support, Surveys and Questionnaires, Tertiary Care Centers, Young Adult, 46, XX Disorders of Sex Development epidemiology, Disorder of Sex Development, 46,XY epidemiology, Quality of Life
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Objective: Few studies have focused on the quality of life (QoL) of patients with disorders of sex development (DSD). Our aim was to evaluate QoL in DSD patients with defined diagnoses followed until adulthood in a single tertiary centre., Patients and Methods: Adult patients with DSD (56 patients with 46,XX DSD - 49 with female social sex and 7 with male social sex as well as 88 patients with 46,XY DSD - 54 with female social sex and 34 with male social sex)., Measurements: QoL using WHOQOL-Bref questionnaire., Results: Both patients with 46,XX DSD and patients with 46,XY DSD had similar QoL scores on the WHOQOL-Bref, comparable to the scores of the Brazilian general population. The chronological age at the start of treatment was negatively and significantly associated with general QoL score. Patients with male social sex DSD had better scores on the psychological domain than patients with female social sex DSD, as found in the Brazilian general population. In addition, among the 46,XY DSD group, the male social sex patients had better QoL compared with the female social sex patients. There was a positive and significant correlation between sexual performance and general QoL, although it explained only 4% of the variability of the general QoL score. The most influencing variables were general health, positive feelings and spirituality, religion and personal beliefs, each of them contributing with 18% of the variability of the general QoL score., Conclusion: Our large cohort of adult patients with DSD, which was followed by a multidisciplinary team in a single tertiary centre, had good QoL in adulthood; in addition, late treatment compromised the QoL of patients with DSD, whereas sexual performance has little influence on QoL., (© 2014 John Wiley & Sons Ltd.)
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- 2015
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18. Acne and PCOS are less frequent in women with Mayer-Rokitansky-Küster-Hauser syndrome despite a high rate of hyperandrogenemia: a cross-sectional study.
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Rall K, Conzelmann G, Schäffeler N, Henes M, Wallwiener D, Möhrle M, and Brucker SY
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- 46, XX Disorders of Sex Development diagnosis, Acne Vulgaris diagnosis, Adolescent, Adult, Congenital Abnormalities diagnosis, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Hyperandrogenism diagnosis, Incidence, Polycystic Ovary Syndrome diagnosis, Surveys and Questionnaires, Young Adult, 46, XX Disorders of Sex Development epidemiology, Acne Vulgaris epidemiology, Congenital Abnormalities epidemiology, Hyperandrogenism epidemiology, Mullerian Ducts abnormalities, Polycystic Ovary Syndrome epidemiology
- Abstract
Background: Acne is a very common skin condition during adolescence and adulthood. Patients with uterovaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome, MRKH) treated at the Tübingen University Center for Rare Female Genital Malformations, however, clinically appeared to be less frequently affected by acne. The etiology of MRKH syndrome remains unknown. The only known MRKH-associated mutations are located within the WNT4 gene and lead to an atypical form of MRKH syndrome associated with clinical and biochemical hyperandrogenism. Our study aimed to assess the frequency, severity, and self-evaluation of acne in MRKH patients and to correlate the clinical findings with hormone analyses., Methods: As part of a cross-sectional longterm follow-up study after laparoscopic assisted creation of a neovagina a questionnaire was sent to 149 MRKH patients aged 16-44 years comprising 26 items concerning prevalence and self-evaluation of acne, and the effects of acne on quality of life. The questionnaire was derived from one used in a former epidemiological study of acne in 4,000 women. Blood for hormone analyses was collected routinely during the clinical visit., Results: Fully completed, evaluable questionnaires were returned by 69/149 (46%) women. Of these respondents, 42 (60.1%) showed hyperandrogenemia without other clinical signs of virilization but only 17 (24.6%) reported acne (8 (11.6%) had physiological acne and 9 (13.0%) clinical acne) and only 10 (14.5%) reported receiving medical treatment for their acne. Effects of acne on quality of life were minor. Only 4 patients (5.8%) with PCOS were identified, among them one with physiological acne, the other three within the acne-free group., Conclusions: Although hyperandrogenemia is common, acne is significantly less frequent in women with MRKH than reported in the literature for non-MRKH women, and is seldom treated medically. Patients in this study appeared resistant to acne to some extent, possibly due to the sebaceous glands in the acne regions being less sensitive to androgens compared to the normal population. A WNT4 mutation is unlikely to be the main cause of MRKH syndrome in our hyperandrogenemic patients.
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- 2014
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19. Development of a provisional model to improve transitional care for female adolescents with a rare genital malformation as an example for orphan diseases.
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Simoes E, Kronenthaler A, Emrich C, Rieger MA, Rall KK, Schäffeler N, Hiltner H, Ueding E, and Brucker SY
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- 46, XX Disorders of Sex Development psychology, Adolescent, Adult, Congenital Abnormalities psychology, Female, Humans, Mental Disorders epidemiology, Mental Disorders psychology, Rare Diseases psychology, Surveys and Questionnaires, Young Adult, 46, XX Disorders of Sex Development epidemiology, Congenital Abnormalities epidemiology, Health Services, Mullerian Ducts abnormalities, Rare Diseases epidemiology
- Abstract
Deficits of care exist during the transitional period, when young people with ongoing needs of support to achieve their physical, social, and psychological potential are entering adulthood. This study aims to develop a patient oriented, structured provisional model to improve transitional care for adolescents with Mayer-Rokitansky-Kuester-Hauser-Syndrome as an example for orphan diseases, where problems of access and continuity are even more complex. The study is funded by the German Federal Ministry of Education and Research (BMBF-Funding Code 01GY1125). The target patient group are young females with this disorder, treated at the Centre for Rare Genital Malformations in Women (ZSGF), University Hospital of Tuebingen. The study comprises five phases: an appraisal of literature, assessment of patients (n = 25), parents', partners', and health and social care providers' (n = 24) needs and experienced deficits in care and support in a qualitative approach, construction of a provisional model via scenario technique, followed by communicative validation (including interested public, n = 100), preference finding, and identification of patient-oriented quality aims for follow-up. Quantitative data from questionnaires and chart review (as sociodemographic data, nonresponder analysis, and preference rating) are worked up for descriptive statistics. The results provide a platform for the development of future multidisciplinary transitional intervention programs in orphan diseases.
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- 2014
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20. Disorders of sex development among Sudanese children: 5-year experience of a pediatric endocrinology clinic.
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Abdullah MA, Saeed U, Abass A, Lubna K, Weam A, Ali AS, and Elmwla IF
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- 46, XX Disorders of Sex Development etiology, 46, XX Disorders of Sex Development therapy, Adolescent, Adrenal Hyperplasia, Congenital etiology, Adrenal Hyperplasia, Congenital therapy, Androgen-Insensitivity Syndrome radiotherapy, Androgen-Insensitivity Syndrome therapy, Child, Child, Preschool, Disorder of Sex Development, 46,XY etiology, Disorder of Sex Development, 46,XY therapy, Female, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, Sex Factors, Sex Reassignment Surgery, Sudan epidemiology, 46, XX Disorders of Sex Development epidemiology, Adrenal Hyperplasia, Congenital epidemiology, Androgen-Insensitivity Syndrome epidemiology, Disorder of Sex Development, 46,XY epidemiology
- Abstract
Background: The birth of a child with disorders of sex development (DSDs) is considered a medical and psychosocial emergency. Management of these cases requires facilities and a multidisciplinary team. In developing countries, this is made difficult by the lack of facilities in addition to sociocultural and religious factors that can affect management. This is the first experience to be published from Sudan., Objective: The aim of this study was to see the prevalence, etiological factors, management, and problems faced in handling these cases., Methods: This is a retrospective descriptive study reviewing the records of all cases referred to a pediatric endocrinology clinic over a 5-year period. Cases were managed by a multidisciplinary team., Results: One hundred fifty-six cases were seen, of which 122 were included in the study. A total of 79 (64.8%) were born at home, whereas 59 (52.2%) of the cases were not observed at birth by health-care providers. The average cost of investigating a case was $250-300. The investigations showed that 69 had XX DSD and 45 had XY DSD. The most common cause of XX DSD was congenital adrenal hyperplasia and that of XY DSD was androgen insensitivity syndrome. Twenty-three (19%) needed sex reassignment. There was a preference for the male sex., Conclusion: DSDs are not uncommon in Sudan. Because of lack of awareness and sociocultural reasons cases are referred late. Investigating these cases is expensive and has to be supported, and more multidisciplinary teams have to be trained to make services accessible and affordable.
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- 2012
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21. High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia.
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Nik-Zainal S, Strick R, Storer M, Huang N, Rad R, Willatt L, Fitzgerald T, Martin V, Sandford R, Carter NP, Janecke AR, Renner SP, Oppelt PG, Oppelt P, Schulze C, Brucker S, Hurles M, Beckmann MW, Strissel PL, and Shaw-Smith C
- Subjects
- Adolescent, Adult, Cohort Studies, Female, Genetic Testing, Humans, Incidence, Kidney abnormalities, Mullerian Ducts abnormalities, Somites abnormalities, Spine abnormalities, Syndrome, Uterus abnormalities, Vagina abnormalities, Young Adult, 46, XX Disorders of Sex Development epidemiology, 46, XX Disorders of Sex Development genetics, Abnormalities, Multiple epidemiology, Abnormalities, Multiple genetics, Chromosome Deletion, Congenital Abnormalities epidemiology, Congenital Abnormalities genetics, DNA Copy Number Variations
- Abstract
Background: Congenital malformations involving the Müllerian ducts are observed in around 5% of infertile women. Complete aplasia of the uterus, cervix, and upper vagina, also termed Müllerian aplasia or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, occurs with an incidence of around 1 in 4500 female births, and occurs in both isolated and syndromic forms. Previous reports have suggested that a proportion of cases, especially syndromic cases, are caused by variation in copy number at different genomic loci., Methods: In order to obtain an overview of the contribution of copy number variation to both isolated and syndromic forms of Müllerian aplasia, copy number assays were performed in a series of 63 cases, of which 25 were syndromic and 38 isolated., Results: A high incidence (9/63, 14%) of recurrent copy number variants in this cohort is reported here. These comprised four cases of microdeletion at 16p11.2, an autism susceptibility locus not previously associated with Müllerian aplasia, four cases of microdeletion at 17q12, and one case of a distal 22q11.2 microdeletion. Microdeletions at 16p11.2 and 17q12 were found in 4/38 (10.5%) cases with isolated Müllerian aplasia, and at 16p11.2, 17q12 and 22q11.2 (distal) in 5/25 cases (20%) with syndromic Müllerian aplasia., Conclusion: The finding of microdeletion at 16p11.2 in 2/38 (5%) of isolated and 2/25 (8%) of syndromic cases suggests a significant contribution of this copy number variant alone to the pathogenesis of Müllerian aplasia. Overall, the high incidence of recurrent copy number variants in all forms of Müllerian aplasia has implications for the understanding of the aetiopathogenesis of the condition, and for genetic counselling in families affected by it.
- Published
- 2011
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