RESUMO
Pure gonadal dysgenesis is a situation when the karyotype is 46, XY, but for various reasons there is a disorder of differentiation of Wolffian and Mullerian structures and in consequence the phenotype is female. It is known that abdominal gonads and the presence of Y chromosome allow to qualify this condition as a high risk of tumor. In most cases breast development is limited because of lack or low level of estrogen. A 27-year-old patient with differences of sexual development (DSD), was admitted to the Department of Endocrinological Gynecology for a control examination. In the history: dysgerminoma, primary amenorrhea and ambiguous karyotype. The patient has not taken hormonal replacement therapy. The breast development is Tanner stage V.
Assuntos
Disgerminoma , Disgenesia Gonadal 46 XY , Disgenesia Gonadal , Neoplasias Ovarianas , Disgerminoma/diagnóstico , Feminino , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/patologia , Disgenesia Gonadal 46 XY/diagnóstico , Disgenesia Gonadal 46 XY/genética , Disgenesia Gonadal 46 XY/patologia , Gônadas/patologia , Humanos , Neoplasias Ovarianas/patologiaRESUMO
Reproductive health of men has declined over time including reduced semen quality specifically sperm count, increased incidence of infertility, and testicular cancers. Our recent findings suggest that these disease states possibly arise as a result of disruption of testicular stem cells biology by perinatal insults including exposure to endocrine disrupting chemicals. Testicular stem cells include relatively quiescent, very small embryonic-like stem cells (VSELs), and actively dividing spermatogonial stem cells (SSCs). Both VSELs and SSCs express estrogen receptors and are directly vulnerable to endocrine disruption. Exposing mice pups to estradiol (20 µg/pup/day on days 5-7) or diethylstilbestrol (2 µg/pup/day on days 1-5) affected spermatogenesis during adult life with reduced numbers of tubules in stage VIII, tetraploid cells and sperm. These mice were infertile and majority of diethylstilbestrol treated mice revealed testicular cancer-like changes. An increase in VSEL numbers, observed by both flow cytometry and qRT-PCR, was associated with marked reduction of c-KIT positive spermatogonial cells. VSELs undergo epigenetic changes due to endocrine disruption that results in blocked differentiation (impaired spermatogenesis) leading to reduced sperm count and infertility, and their excessive self-renewal initiates cancer-like changes in adult life. Thus, testicular dysgenesis syndrome (TDS) has a stem cell rather than a genetic basis.
Assuntos
Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Disgenesia Gonadal/induzido quimicamente , Infertilidade Masculina/etiologia , Saúde do Homem , Saúde Reprodutiva , Células-Tronco/efeitos dos fármacos , Testículo/efeitos dos fármacos , Fatores Etários , Animais , Diferenciação Celular/efeitos dos fármacos , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/metabolismo , Disgenesia Gonadal/fisiopatologia , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Masculino , Fatores de Risco , Espermatogênese/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/patologia , Síndrome , Testículo/metabolismo , Testículo/patologiaRESUMO
Ectopic splenic tissue in any location could represent accessory spleen, a common congenital abnormality, splenosis, the presence of numerous nodules of ectopic splenic tissue after spleen trauma/surgery or splenogonadal fusion, a rare congenital malformation found mostly in males. Ectopic splenic tissue in the ovary is usually found in the context of an extensive pelvic splenosis. Solitary ovarian splenosis presenting not as a part of pelvic splenosis, but rather as a solitary mass masquerading an ovarian tumor is extremely rare. Differential diagnosis in this case includes mostly splenosis and splenogonadal fusion of the discontinuous type. Relevant literature and possible pathogenesis are discussed.
Assuntos
Coristoma/patologia , Doenças Ovarianas/patologia , Baço , Coristoma/diagnóstico , Feminino , Disgenesia Gonadal/diagnóstico , Humanos , Pessoa de Meia-Idade , Doenças Ovarianas/diagnóstico , Esplenose/diagnósticoRESUMO
Disorders of sex development (DSD) are defined as discrepancy between chromosomal, gonadal and anatomic sex. The basic principles for the management of DSD include a multidisciplinary approach for gender assignment. Clinical assessment includes a detailed history and examination of external genitalia. Most of the disorders with symmetrical gonades indicate hormonal cause while asymmetrical gonades are found in chromosomal DSDs. Karyotyping will indicate a 46XX DSD, 46 XY DSD or mosicism. Internal anatomy is defined by ultrasonography, genitoscopy and laparoscopy. Human chorionic gonadotrophins (hCG) stimulation test is carried out in under-virilised males to see the function of Leydig cells in testes. The Most common cause of 46XX DSD is congenital adrenal hyperplasia (CAH). The decision of gender assignment surgery is to be taken in a multidisciplinary environment and with informed consent of the parents. Most of 46 XX CAH patients, even if markedly virilised, and 46 XY complete androgen insensitivity syndrome are raised as females. Similarly, most of 5-α reductase deficiency and 17-ß hydroxysteroid dehydrogenase deficiency patients are assigned to the male gender. The decision in cases of mixed gondal dysgenesis and ovotesticular DSD is based on the development of external and internal genitalia. Patients with androgen biosynthetic defects, partial androgen insensitivity syndrome are usually assigned to the male gender.
Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , 17-Hidroxiesteroide Desidrogenases/deficiência , Hiperplasia Suprarrenal Congênita/diagnóstico , Síndrome de Resistência a Andrógenos/diagnóstico , Colestenona 5 alfa-Redutase/deficiência , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Feminino , Disgenesia Gonadal/diagnóstico , Ginecomastia/diagnóstico , Humanos , Cariotipagem , Masculino , Erros Inatos do Metabolismo de Esteroides/diagnósticoRESUMO
Patients with complete XY gonadal dysgenesis (GD) show a high predisposition to germ cell tumors (GCT). Patients with coexistence of GCT and GD have been reported previously. Here we present a 15-year-old girl with mixed GCT and GD who also developed an intra-abdominal synovial sarcoma one year after the treatment. This is the first report, to our knowledge, of synovial sarcoma associated with XY GD.
Assuntos
Neoplasias Abdominais/diagnóstico , Disgenesia Gonadal/diagnóstico , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Ovarianas/diagnóstico , Sarcoma Sinovial/diagnóstico , Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/cirurgia , Adolescente , Criança , Evolução Fatal , Feminino , Humanos , Metástase Linfática , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Sarcoma Sinovial/tratamento farmacológico , Sarcoma Sinovial/cirurgiaRESUMO
PURPOSE: In this report, we characterize the timing and behavior of malignant ovarian germ cell tumors (GCTs) in pediatric patients with dysgenetic gonads compared to those with normal gonadal development. PATIENTS AND METHODS: Patients from the Children's Oncology Group AGCT0132 with malignant ovarian GCTs were included. Within this population, we sought to identify patients with gonadoblastoma, streak ovaries, or other evidence of gonadal dysgenesis (GD). Patients with malignant GCTs containing one or more of the following histologies-yolk sac tumor, embryonal carcinoma, or choriocarcinoma-were included. Patients were compared with respect to event-free survival (EFS) and overall survival (OS). RESULTS: Nine patients with GD, including seven with gonadoblastoma (mean age, 9.3 years), were compared to 100 non-GD patients (mean age, 12.1 years). The estimated 3-year EFS for patients with GD was 66.7% (95% CI 28.2-87.8%) and for non-GD patients was 88.8% (95% CI 80.2-93.8%). The estimated 3-year OS for patients with GD was 87.5% (95% CI 38.7-98.1%) and for non-GD patients was 97.6% (95% CI of 90.6-99.4%). CONCLUSION: Patients presenting with nongerminomatous malignant ovarian GCTs in the context of GD have a higher rate of events and death than counterparts with normal gonads. These findings emphasize the importance of noting a contralateral streak ovary or gonadoblastoma at histology for any ovarian GCT and support the recommendation for early bilateral gonadectomy in patients known to have GD with Y chromosome material. In contrast to those with pure dysgerminoma, these patients may represent a high-risk group that requires a more aggressive chemotherapy regimen.
Assuntos
Disgenesia Gonadal/mortalidade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Ovarianas/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/patologia , Disgenesia Gonadal/terapia , Humanos , Lactente , Recém-Nascido , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Taxa de SobrevidaRESUMO
We report a novel syndromic disorder of sex development observed in three male siblings, presenting with the association of micropenis without hypospadias, cryptorchidism, very low level of antimüllerian hormone in the neonatal period, and no persistent müllerian duct structures, suggesting a progressive regression of testicular function. The patients described here showed a striking neurological involvement including bilateral periventricular cysts observed in the anterior part of the frontal horns prenatally and increasing in size and number over time, associated with infra and supratentorial parenchymal atrophy, dilated ventricular system, corpus callosum hypoplasia, severe intellectual disability, and epilepsy. Associated features included a distinctive facies, joint contractures, retinopathy, and hearing loss. Pathological examination was consistent with testicular dysgenesis and leukoencephalopathy with spongiosis and microcalcifications. To the best of our knowledge, this disease, characterized by a recognizable pattern of malformations, has not been previously reported. An exhaustive genetic and metabolic evaluation was normal. Autosomal recessive inheritance was considered to be likely, on the basis of SNP studies. We hope that the detailed description provided here of the clinical, radiological, and pathological findings observed in this family will help to identify further unrelated patients, and ultimately, to clarify the genetic basis of this condition. © 2017 Wiley Periodicals, Inc.
Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/genética , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/genética , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/genética , Fenótipo , Testículo/anormalidades , Encéfalo/patologia , Pré-Escolar , Fácies , Evolução Fatal , Doenças dos Genitais Masculinos/patologia , Hormônios Esteroides Gonadais/sangue , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Pênis/anormalidades , Pênis/patologia , Irmãos , SíndromeRESUMO
Recent studies on gonadal histology have improved the understanding of germ cell malignancy risk in patients with disorders of sex development (DSD), and evidence-based gonadal management strategies are gradually emerging. Especially in 46,XY DSD and 45,X/46,XY DSD, which are characterized by gonadal dysgenesis, the risk of germ cell malignancy is significantly increased. This paper summarized the progress over the past 10 years in malignancy risk assessment in patients with DSD, and its implications for optimal surgical handling of the involved gonads.
Assuntos
Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/cirurgia , Criança , Árvores de Decisões , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Urológicos/métodosRESUMO
Mutation of the Wilms tumor suppressor gene (WT1) has been recognized as one of the etiologies of steroid-resistant nephrotic syndrome (SRNS). The mutation is also responsible for gonadal dysgenesis in 46,XY individuals. Early recognition of the presence of Y chromosome is of particular importance because of the high risk of gonadal tumor. We present here three cases of steroid-resistant nephrotic syndrome with WT1 mutation and 46,XY karyotype. Patient 1 and 2 have intron splice site (IVS9+5G A) mutation. Patient 3 has c.1301GA (p. R434H) mutation. All cases had normal female external genitalia at birth and eluded the diagnosis of gonadal dysgenesis until later in life. We suggest that chromosomal analysis should be promptly performed in female patients with early-onset steroid-resistant nephrotic syndrome.â©.
Assuntos
Disgenesia Gonadal/genética , Síndrome Nefrótica/genética , Proteínas WT1/genética , Anormalidades Múltiplas , Adolescente , Pré-Escolar , Resistência a Medicamentos , Feminino , Disgenesia Gonadal/diagnóstico , Humanos , Lactente , Mutação , Síndrome Nefrótica/tratamento farmacológico , EsteroidesAssuntos
Infecções por Chlamydia , Chlamydia trachomatis/isolamento & purificação , Tubas Uterinas , Disgenesia Gonadal , Laparoscopia/métodos , Ovário , Doença Inflamatória Pélvica , Adulto , Infecções por Chlamydia/complicações , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/fisiopatologia , Tubas Uterinas/anormalidades , Tubas Uterinas/diagnóstico por imagem , Feminino , Disgenesia Gonadal/complicações , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/fisiopatologia , Humanos , Ovário/anormalidades , Ovário/diagnóstico por imagem , Doença Inflamatória Pélvica/complicações , Doença Inflamatória Pélvica/diagnóstico , Doença Inflamatória Pélvica/microbiologia , Doença Inflamatória Pélvica/fisiopatologia , Resultado do TratamentoRESUMO
Puberty is a defining time of many adolescents' lives. It is a series of events that includes thelarche, pubarche, and menarche. Primary amenorrhea is the absence of menarche. There are numerous etiologies including outflow tract obstructions, gonadal dysgenesis, and anomalies of the hypothalamic axis. This review's aims are to define primary amenorrhea and describe the various causes, their workups, associated comorbidities, and treatment options. At the end, a generalist should be able to perform an assessment of an adolescent who presents with primary amenorrhea and, if warranted, begin initial treatment.
Assuntos
Amenorreia/etiologia , Amenorreia/terapia , Genitália Feminina/anormalidades , Disgenesia Gonadal/complicações , Ovário/anormalidades , Doenças da Hipófise/complicações , Adeno-Hipófise , Adolescente , Amenorreia/diagnóstico , Feminino , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/terapia , Humanos , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/terapia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapiaRESUMO
STUDY QUESTION: What is the optimal protocol of management for phenotypic female patients with Y chromosome or Y-derived sequences, in particular for adult patients? SUMMARY ANSWER: Immediate gonadectomy, long-term hormone therapy and psychological care are suggested to be the optimal management for older phenotypic female patients with Y chromosome or Y-derived sequences. WHAT IS KNOWN ALREADY: Phenotypic female patients with Y chromosome or Y-derived sequences are at increasing risk of developing gonadal tumors with age. Early diagnosis and safe guidelines of management for these patients are needed. STUDY DESIGN, SIZE, DURATION: One hundred and two phenotypic women with Y chromosome or Y-derived sequences were included in a straightforward, retrospective-observational study conducted over a period of 26 years from January 1985 to November 2010. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Patients aged 16-34 years presenting to our Academic Department of Gynecology with symptoms of disorders of sex development were subjected to history taking, hormonal evaluation, conventional cytogenetic analysis, PCR, histopathology and immunohistochemistry. Features of the gonads were examined and the outcome of prophylactic gonadectomy evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Among the patients recruited in our study, 48 patients (47.1%) were diagnosed with complete/partial androgen insensitivity syndrome (CAIS/PAIS) (46XY), 33 cases (32.4%) with gonadal dysgenesis (46XY) and the remaining subjects (20.1%) with mixed gonadal dysgenesis (with sex chromosome structural abnormalities). The total incidence of malignancy was 17.6%. Seventeen patients (16.7%) had gonadoblastoma, while one patient (1.0%) with gonadal dysgenesis had dysgerminoma. Gonadoblastoma were observed in 2/21 patients with sex chromosome structural abnormalities (9.5%), 3/33 patients with gonadal dysgenesis (9.1%), 9/30 patients with CAIS (30.0%) and 3/18 patients with PAIS (16.7%). LIMITATIONS, REASONS FOR CAUTION: Selection bias in this cohort study may affect data interpretation due to the low incidence of disorders of sex development in the general population. WIDER IMPLICATIONS OF THE FINDINGS: The risk for malignant transformation may occur in early life and highly increase with age in patients with Y chromosome or Y-derived sequences. Optimal timing of gonadectomy should be decided by multiple factors including the subgroup of disorder, age and degree of patient's maturity. In addition, gonadal biopsy is suggested when the disease is diagnosed and any evidence of premalignancy warranties gonadectomy. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Scientific Research Project (2013CB967404), Natural Science Funds of Zhejiang Province (Y13H04005), Zhejiang Qianjiang talent plan (2013R10027), the Fundamental Research Funds for the Central Universities and Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period (2012BAI32B04). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER None.
Assuntos
Cromossomos Humanos Y/ultraestrutura , Transtornos Gonadais/genética , Gonadoblastoma/genética , Adolescente , Adulto , Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/genética , Aberrações Cromossômicas , Citogenética , Feminino , Genitália/patologia , Transtornos Gonadais/diagnóstico , Transtornos Gonadais/cirurgia , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/genética , Gonadoblastoma/diagnóstico , Gonadoblastoma/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Fenótipo , Estudos Retrospectivos , Risco , Fatores Sexuais , Adulto JovemRESUMO
Congenital uterine anomalies are often asymptomatic. They may present with infertility, recurrent miscarriage, preterm delivery, abnormal lie in pregnancy and other obstetric complications. We report the case of a 38-year old patient with unicornuate uterus without rudimentary horn and with unilateral left ovarian agenesis and unilateral left renal agenesis who gave birth to eleven children. Anomaly was incidentally diagnosed during laparoscopic sterilization.
Assuntos
Laparoscopia/métodos , Ovário/anormalidades , Útero/anormalidades , Adulto , Feminino , Disgenesia Gonadal/diagnóstico , Humanos , Achados Incidentais , Rim/anormalidadesRESUMO
BACKGROUND: Gonadoblastoma (GB) is regarded as an in situ form of germ cell tumor in dysgenetic gonads, and 30% of patients with GB develop a dysgerminoma/seminoma tumor. OBJECTIVE: Determine whether OCT3/4 and ß-catenin are expressed in dysgenetic gonads before GB development and whether TSPY participates in the OCT3/4-ß-catenin pathways in the malignant invasive behavior. METHODS: dysgenetic gonads of Disorders of sex differentiation (DSD) patients with mixed gonadal dysgenesis were analyzed by immunohistochemistry and immunofluorescence for comparison with GB and dysgerminoma/seminoma. RESULTS: Our results suggest that the development of GB is secondary to the interaction of OCT3/4 and TSPY, that ß-catenin does not participate in this process. CONCLUSIONS: The use of this biological markers detects the potential high risk gonads.
Assuntos
Biomarcadores Tumorais/análise , Proteínas de Ciclo Celular/análise , Disgenesia Gonadal/diagnóstico , Gonadoblastoma/diagnóstico , Neoplasias de Tecido Gonadal/diagnóstico , Fator 3 de Transcrição de Octâmero/análise , beta Catenina/análise , Estudos de Casos e Controles , Criança , Disgerminoma/diagnóstico , HumanosRESUMO
Incomplete polyorchidism (also called bilobed testicle) is an extremely uncommon congenital anomaly. Only 3 cases of bilobed testicle were previously reported in the available literature. We describe a case of a 4-year-old boy who presented with a 6-month history of an asymptomatic scrotal mass located in the upper pole of the left testicle mimicking testicular tumour. After partial orchiectomy, macroscopic and pathological examination of the lesion confirmed the diagnosis of normal testicular tissue.
Assuntos
Disgenesia Gonadal/diagnóstico , Neoplasias Testiculares/diagnóstico , Testículo/anormalidades , Pré-Escolar , Diagnóstico Diferencial , Humanos , MasculinoRESUMO
OBJECTIVE: To determine the frequency of XY karyotypes among females with complete gonadal dysgenesis (CGD) and to investigate the frequency of both gonadal tumors and SRY mutations. DESIGN: Retrospective study based on data from all patients with CGD seen in our service from 1989 to 2010. SETTING: Clinic for disorders of sex development, University Hospital, State University of Campinas. PATIENT(S): Thirty-two patients with hypergonadotropic hypogonadism, streak gonads, internal and external female genitalia, and normal karyotype (46,XX or 46,XY); 31 were index cases and 29 did not have a previously determined karyotype. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): The percentage of XY karyotypes among patients with CGD was 34.5% (10/29). Mean age at diagnosis among XY and XX patients was 17.4 years and 19.9 years, respectively. Gonadal tumors were found in 4 of 9 XY girls, and 7 of 10 had SRY gene mutations. CONCLUSION(S): The previously unreported finding of an elevated frequency of 46,XY karyotype among patients with CGD and the high risk of gonadal neoplasia in such cases indicate that this diagnosis must be kept in mind by clinicians and strengthen the importance of karyotype analysis in females with primary hypogonadism. In addition, the frequency of SRY mutations in XY CGD might be higher than previously considered.
Assuntos
Disgenesia Gonadal 46 XY/epidemiologia , Disgenesia Gonadal/epidemiologia , Adolescente , Adulto , Idade de Início , Criança , Feminino , Genes sry , Disgenesia Gonadal/classificação , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/genética , Disgenesia Gonadal 46 XY/diagnóstico , Disgenesia Gonadal 46 XY/genética , Humanos , Cariótipo , Prática Profissional/estatística & dados numéricos , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: Diagnosis of dysgerminoma in the paediatric age group is uncommon, and most cases arise from dysgenetic gonads of 46, XY pure gonadal dysgenesis (PGD) patients. Bilateral gonadectomy is mandatory in these patients. So, the preoperative diagnosis of PGD is important in order to avoid multiple surgical procedures and delayed patient information in the case of a suspected 'ovarian' tumour. Our aim was to discuss preoperative clues that can lead to suspicion of dysgerminoma in the context of PGD. MATERIALS AND METHODS: We reviewed the charts of six patients treated for dysgerminoma associated with 46, XY PGD. We focused on particularities of clinical and biological evaluations. RESULTS: Median age at diagnosis was 11 years. Pubertal development was absent or incomplete even at late ages. Dysgerminoma was associated with gonadoblastoma foci in all cases. Tumoral marker profile was a normal alfafetoprotein level, a high lactate dehydrogenase level and normal or moderate human chorionic gonadotropin (ßHCG) secretion, except for one patient who had a mixed tumour with notably a choriocarcinoma share (high ßHCG). Follicle-stimulating hormone (FSH) level was very high in all patients tested and, interestingly, also in one prepubertal patient. CONCLUSIONS: In the case of a suspected ovarian tumour, delayed pubertal development, moderate ßHCG level and elevated FSH level are clinical and biological clues to a diagnosis of dysgerminoma in the context of PGD and should prompt karyotype analysis before surgery. Because FSH is an efficient indirect marker of this condition, we suggest including this analysis in the management of gonadal tumours.
Assuntos
Árvores de Decisões , Disgerminoma/diagnóstico , Disgenesia Gonadal/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adolescente , Biomarcadores Tumorais/sangue , Criança , Disgerminoma/etiologia , Feminino , Hormônio Foliculoestimulante/sangue , Disgenesia Gonadal/complicações , Humanos , Neoplasias Ovarianas/etiologia , Estudos RetrospectivosAssuntos
Amenorreia/diagnóstico , Adolescente , Hiperplasia Suprarrenal Congênita/diagnóstico , Adulto , Amenorreia/etiologia , Síndrome de Resistência a Andrógenos/diagnóstico , Criança , Feminino , Genitália Feminina/anormalidades , Disgenesia Gonadal/diagnóstico , Humanos , Hiperprolactinemia/diagnóstico , Hipogonadismo/diagnóstico , Doenças Hipotalâmicas/diagnóstico , Neoplasias Hipotalâmicas/diagnóstico , Masculino , Ciclo Menstrual/fisiologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Hipofisárias , Síndrome do Ovário Policístico/diagnóstico , Insuficiência Ovariana Primária/diagnóstico , Puberdade Tardia/diagnóstico , Doenças Uterinas/diagnóstico , Virilismo/diagnósticoRESUMO
A 15-month-old boy was discovered to have internal female genitalia during an operation for bilateral inguinal hernia. The biopsies showed normal testicular tissue and the karyotyping result was 46XY, so the diagnosis of persistent mullerian duct syndrome (PMDS) was made. At the second operation, the uterine fundus and fallopian tubes were excised. Then, he underwent bilateral orchiopexy. We discuss a rare presentation of this disorder, its management, and genetic implications together with a review of the literature.
Assuntos
Coristoma/cirurgia , Disgenesia Gonadal/cirurgia , Hérnia Inguinal/cirurgia , Ductos Paramesonéfricos/anormalidades , Testículo , Coristoma/diagnóstico , Disgenesia Gonadal/diagnóstico , Humanos , Lactente , Masculino , SíndromeRESUMO
The pathways leading to female sexual determination in mammals are incompletely defined. Loss-of-function mutations in the WNT4 gene appear to cause developmental abnormalities of sexual differentiation in women and mice. We recruited six patients with different degrees of Müllerian abnormalities, with or without renal aberrations and a normal female 46,XX karyotype. A clear androgen excess was found only in one patient. This 19-year-old woman was affected by primary amenorrhoea, absence of Müllerian ducts derivatives, clinical (acne and hirsutism) and biochemical (repeatedly high levels of testosterone) signs of androgen excess. Direct sequencing of her WNT4 gene followed by functional studies in human ovarian cells (OVCAR3) was performed. This patient carried the novel R83C loss-of-function dominant negative mutation in her WNT4, confirming the role of WNT4 in the development and maintenance of the female phenotype in women. Our study can also help refine the phenotype of WNT4 deficiency in humans. In fact, it appears that at least in this limited casuistic small group of patients, the absence of a uterus (and not other Müllerian abnormalities) and the androgen excess are the pathognomonic signs of WNT4 defects, suggesting that this might be a clinical entity distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome.