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The normal embryological development, anatomical structural setup and physiological functionality of the genital system...

We analyzed three cases of Complete Androgen Insensitivity Syndrome (CAIS) and report three hitherto undisclosed causes of the disease. RNA-Seq, Real-timePCR, Western immunoblotting, and immunohistochemistry were performed with the aim of characterizing the disease-causing variants. In case No.1, we have identified a novel androgen receptor (AR) mutation (c.840delT) within the first exon in the N-terminal transactivation domain. This thymine deletion resulted in a frameshift and thus introduced a premature stop codon at amino acid 282. In case No.2, we observed a nonsynonymous mutation in the ligand-binding domain (c.2491C&gt, T). Case No.3 did not reveal AR mutation, however, we have found a heterozygous mutation in CYP11A1 gene, which has a role in steroid hormone biosynthesis. Comparative RNA-Seq analysis of CAIS and control revealed 4293 significantly deregulated genes. In patients with CAIS, we observed a significant increase in the expression levels of PLCXD3, TM4SF18, CFI, GPX8, and SFRP4, and a significant decrease in the expression of SPATA16, TSACC, TCP10L, and DPY19L2 genes (more than 10-fold, p &lt, 0.05). Our findings will be helpful in molecular diagnostics of patients with CAIS, as well as the identified genes could be also potential biomarkers for the germ cells differentiation process.

Androgen insensitivity syndrome (AIS) is a congenital disorder in which a defect in the androgen receptor (AR) gene leads to cellular resistance to androgens. Defects in the AR gene, located on the X chromosome, result in the development of a feminine phenotype in chromosomally male (46, XY) individuals. In this case report, we present a 44 years old patient with complete androgen insensitivity syndrome (CAIS) initially presenting with primary amenorrhea. The patient underwent a full clinical evaluation, revealing hypoplastic vagina and a lack of uterus and ovaries. Hormonal evaluation revealed markedly elevated testosterone, FSH, and LH serum concentrations. Diagnostic imaging, including pelvic MRI, confirmed the presence of two solid masses in the inguinal canals (right 26 × 13 mm, left 25 × 15 mm). The patient underwent genetic testing, revealing a 46 XY karyotype and an as of yet unprecedented androgen receptor mutation. The type of the mutation was a single-base exchange - the substitution from cytosine to thymine in chromosome X:66942710 position (referred to human reference genome GRCh37), which has resulted in an amino acid changes from leucine (CTT) to phenyloalanine (TTT) in ligand-binding domain.

ResumenEl término “desorden en la diferenciación sexual” (DDS) representa un grupo de anormalidades en el desarrollo del tracto genitourinario, en el cual ocurre un desarrollo atípico en uno o más niveles: cromosómico, gonadal o anatómico. Los genéticamente varones 46XY pueden presentarse con genitales externos fenotípicamente femeninos o ambiguos. El síndrome de insensibilidad a los andrógenos se podría considerar una enfermedad causada por la resistencia a la acción androgénica, causada por la mutación Xq11-12, que afecta los receptores androgénicos; la presentación clínica dependerá del grado de insensibilidad, leve (masculino infértil), moderada o completa como en nuestro caso. Requiere seguimiento por psicólogo y psiquíatra para familiares y paciente, para un desarrollo psicosexual adecuado, antes y después del tratamiento quirúrgico definitivo.El objetivo del presente artículo es realizar una revisión sistemática de los artículos publicados en la base de datos de Medline, para identificar la epidemiología e incidencia del síndrome de insensibilidad completa a los andrógenos, así como reconocer su abordaje, tratamiento y seguimiento de estos casos.Se presenta paciente de 23 años de edad, sin antecedentes patológicos de importancia, la cual inicia su estudio a los 17 años de edad por el Servicio de Ginecología, por presentar amenorrea y falta de desarrollo en caracteres sexuales secundarios, tiene estudios de imagen sin evidenciar estructuras Müllerianas; se realiza laparoscopía diagnóstica en 2 ocasiones sin poder identificar órganos sexuales femeninos o vestigios de testículos; estudio hormonal con niveles de estrógenos y testosterona evidentemente bajos con hormona folículo estimulante (FSH), hormona luteinizante (LH) y hormona liberadora de gonadotropinas dentro de parámetros normales; el cariotipo reporta 46XY. En ese momento se ofrece apoyo psiquiátrico, se decide continuar con educación femenina, por lo que se resuelve colocación de prótesis mamaria. Finalmente, se nos interconsulta para la realización de vaginoplastía con uso de segmento intestinal como canal vaginal.AbstractThe term “disorders of sexual differentiation” (DSD) encompasses a group of abnormalities in the development of the genitourinary tract. Atypical development occurs at one or more chromosomal, gonadal, or anatomic levels. 46 XY genetic males may present with external genitals that are phenotypically female or ambiguous. Androgen insensitivity syndrome could be considered a disease caused by resistance to androgenic action due to the Xq11-12 mutation that affects the androgenic receptors. Clinical presentation depends on the degree of insensitivity: mild (infertile male), partial, or complete, as with our patient. Psychologic and psychiatric follow-up is required for both the patient and family members so there can be adequate psychosexual development before and after definitive surgical treatment.The aim of this article was to conduct a systematic review of published reports in the MEDLINE database to identify the epidemiology and incidence of complete androgen insensitivity syndrome and to examine the approach, treatment, and follow-up of these cases.We present herein a 23-year-old patient, with an unremarkable pathologic history, who began to be studied by the Gynecology Service at 17 years of age due to amenorrhea and lack of secondary sexual development. Imaging studies failed to show Müllerian structures. Diagnostic laparoscopy was performed on 2 occasions in which female sexual organs or vestiges of testes were unable to be identified. Hormonal study revealed obviously low levels of estrogens and testosterone, and follicle-stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropinreleasing hormone were within normal parameters; 46XY karyotype was reported. Psychiatric support was then offered. It was decided that the patient would continue to be raised and treated as a female and therefore she was given breast implants. Our service was subsequently consulted for performing vaginoplasty using an intestinal segment as the vaginal canal.

Morris Syndrome is a pathological condition which needs a special approach regarding both diagnosis and treatment because of its rarity. While the diagnosis is based on karyotype test, the treatment should follow the idea of harmless and cosmetic benefits as well as complete gonads removal. This paper is presenting the usefulness and advantages of minimally invasive surgery as a feasible treatment for such a disease. A retrospective study was performed for two patients with Morris Syndrome, admitted to the “CI Parhon” National Institute of Endocrinology, Bucharest, Romania, followed-up for 4 - 16 years, and operated to the Department of Surgery, Emergency Hospital, Bucharest, Romania. Patients with primary amenorrhea have been clinically observed and three patients with 46, XY karyotype have been identified as Morris Syndrome cases needing surgical removal of the intraperitoneal gonads because of the risk of malignant transformation. A minimally invasive surgical technique has been chosen for proper treatment: the anterior transperitoneal laparoscopic approach. The surgery was adapted to every case, in according with preoperative imagistic diagnosis of the intraperitoneal testes (localization, dimensions, adjacent organs involvement, surgical access). No postoperative complications were noticed and specimens' pathology confirmed the final diagnosis. Cosmetic benefits were achieved for every young patient as well as rapid postoperative recovery (discharge after 48 hours). The authors concluded that Morris Syndrome patients could benefit from the laparoscopic surgery which is a feasible, safe and proper treatment for such cases.

Congenital absence of the vagina is a rare condition commonly associated with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, Morris Syndrome, and XY sex reversal. Secondarily this condition may be caused by exenteration of various pelvic tumors. Surgical options for treating this devastating condition include external vaginal dilation, internal dilation using traction devices, and vaginal construction using flaps of skin, bladder, or various bowel segments. We describe our innovative surgical technique employing robotic assistance in the creation of a neo-vagina for a young woman with MRKH syndrome. To the best of our knowledge this is the first report of this surgical technique.

25 лет назад умер «неистовый» Эфроимсон, первый генетик человека, которого интересовала, помимо собственно профессиональных проблем, связанных с генетикой, проблема феномена гениальности, который он пытался объяснить с генетико-медицинских позиций, 25 years ago died a "violent" Efroymson, the first man geneticist was interested in, in addition to the professional issues associated with genetics, the phenomenon of genius, which he tried to explain with genetic and medical positions

The Morris syndrome is a X-linked recessive condition due to a complete or partial insensitivity to androgens, resulting in a failure of normal masculinization of the external genitalia in chromosomally male individuals. This failure of virilization can be either complete or partial depending on the amount of residual androgen receptor function. The phenotype of individuals with partial androgen insensitivity syndrome may range from mildly virilized female external genitalia to mildly undervirilized male external genitalia. We describe a case of Partial Androgen Insensitivity Syndrome in a 21–year-old patient with a 46, XY karyotype, bilateral inguinal masses, clitoral enlargement and partial posterior labial fusion. Surgical care consisted of bilateral orchiectomy and plastic surgery of external genitalia. The patient underwent estrogen replacement therapy.

The Morris syndrome. Androgen insensitivity syndrome (AIS) is a genetic disease caused by mutations in the androgen receptor gene. AIS patients are individuals with a 46, XY karyotype. The phenotype consists in female external genitalia, short vagina, absent mullerian structures, and abdominal, inguinal or intralabial primordial testes. Precise diagnosis, that differentiating between complete (CAIS) and partial (PAIS) form, requires clinical and hormonal investigation and is of great importance for appropriate gender assignment. The CAIS has a minimal impact of one in 99,000 births, for the PAIS, however, there aren't some statistics available, but generally it should be with a lower impact, approximately ten times less than CAIS.Key words: Morris syndrome, androgen insensitivity syndrome, CAIS, PAIS, gonadectomy, hormonal replacement therapy, vaginal ipoplasia.Parole chiave: sindrome di Morris, sindrome da insensibilitŕ agli androgeni, CAIS, PAIS, gonadectomia, terapia ormonale sostitutiva, ipoplasia vaginale.

Vaginal agenesis is a rare condition, therefore the incidence of a malignant transformation in the neovagina is extremely low.We report on a 42-year-old patient with Morris' syndrome and urinary bladder neovagina with a history of prolonged infections of the urinary bladder and intertrigo of the perineal region. The biopsy revealed a squamous cell carcinoma arising from the neovagina. The patient underwent combined radio- and chemotherapy and was disqualified from surgical treatment because of the advanced stage of the disease.Because of the high risk of malignant transformations regular follow-ups are necessary in patients with neovagina creation, including gynecological examination, cytological screening, and biopsy if necessary. In addition, urinary bladder does not seem to be a good material for a functional vagina.

OVERVIEWDiagnoses: Familial complete androgen insensitivity syndrome (Morris syndrome or testicular feminization syndrome).Case ID and referral sources: Case 1. Bisceglia's contribution: AMR Seminar no. 48, case 3A. Contributor's file no. 95357-5. Case 2. Bisceglia's contribution: AMR Se

Individuals with androgen insensitivity syndrome have a high risk (20–30%) of developing malignancy in their gonads. Accordingly, bilateral gonadectomy is recommended. In a 17-year-old woman with Swyer syndrome gonads were located as streaks above the pelvic brim. In a 13-year-old with Morris syndrome they were located within the inguinal canals. Bilateral laparoscopic gonadectomy was performed under general anesthesia in both patients without complications. We suggest that in phenotypic females with 46,XY karyotype, the procedure may be performed safely, even with gonads located in inguinal canals.

Background The differential diagnosis between the various forms of violation of a structure of gonadas at the patients with a female phenotype represents a problem, especially at a primary inspection. Method We represent a case of ultrasonographic diagnostics an ovotestis at a true hermaphroditismis in our practice. There was used linear transabdominal and convex transrectal transducers on ultramark-9 device. Results The young woman (17yo) who has addressed to the gynecologist concerning a primary amenorrhoea, was examined by ultrasound in the Hospital. There were detected a male's structure internal sexual ductuses and presence of gonadas located below usual position of ovaries with structure, estimated as a testicula. The Morris syndrome was diagnosed. At the consequent inspection in center, specializing in genetic ultrasound, specific echostructure of the gonadas was detected, appropriated to their mixed structure (ovotestis), thus a true hermaphroditismis with a female phenotype was diagnosed. The consequent karyotyping (46XX/46XY (16:4)) has confirmed the preliminary ultrasonographic diagnosis. Conclusion The sufficient qualification of the sonographist conducting a ultrasonic research, knowledge of a ultrasonographic picture of the this pathology, allows correct diagnostics already before lab stage of an inspection, using even the routine equipment and review.

O transexualismo é caracterizado como uma entidade psiquiátrica, distinta do homossexualismo e travestismo, revendo-se suas manifestações sindrômicas. Discutem-se as duas principais causas etiológicas plausíveis do transexualismo, a saber: a hipótese psicoanalítica fundamentada na regressão psicossexual com estampagem da figura materna e o modelo neuro-endócrino que pressupõe alterações nos centros de identidade sexual do hipotámo. Com base nesta última explicação propõe-se, a exemplo do que parece ocorrer na síndrome de Morris, cujas células (XY) não respondem ao efeito masculinizante da testosterona plasmática, que os transexuais devem possuir mosaicismo detectável ou críptico, quanto aos cromossomos sexuais, nos centros hipotalâmicos de identidade sexual que não respondem à secreção androgênica produzida pela gônada primitiva. Esta possibilidade explicaria a excessiva prevalência da síndrome entre homens, bem como a sua manifestação com feições típicas no sexo masculino e ainda a ocorrência esporádica da síndrome. O estudo citogenético revelou que a frequência (32%) de mosaicismo quanto aos cromossomos sexuais em 25 transexuais é estatisticamente superior aos valores observados em 14 homossexuais e 40 controles normais, nos quais a proporção de mosaicismo é praticamente nula. Considera-se a possibilidade do critério cariotípico constituir valioso subsídio na diagnose da síndrome. By reviewing the syndromic manifestation, transsexualism in characterized as a psychiatric entity, apart from homossexualism and transvestism. The two main feasible etiologic causes of transsexualism are discussed: the psychoanalytical hypothesis based upon psycossexual regression with imprinting of maternal figure and the neuroendocrine model which assumes alterations of the gender role identity centers in the hypothalamus. On the grounds of the latter explanation and after the scheme that seems to occur in the Morris syndrome whose cells (XY) do not respond to the masculinizing effect of plasma testosterone, it is proposed that transsexuals should possess detectable or cryptic sex-chromosome mosaicism affecting hypothalamic centers of gender role identity which do not respond to the androgenic secretion produced by primitive gonad. This possibility explains the excessive prevalence of the syndrome among men, its typical features in the male as well as its sporadic occurrence. Cytogenetic investigation reveals that the frequency (32%) of sex-chromosome mosaicism among 25 transsexuals and 40 normal control people, both groups presenting the proportion of the mosaicism practically null. The karyotypic criterion as a valuable aid in the syndrome diagnosis is considered.

Morphometry was used to study the effect of T-activin on the morphology of the thymus of (CBA X C57BL) F1 mice given 10, 15 and 20 injections of T-activin (1.0 micrograms i.p.). T-activin did not cause any pathological alterations in the thymus. Ten injections of T-activin activated the proliferation and migration of thymocytes from the thymus. Fifteen injections of T-activin eventuated in an increased surge of thymocyte migration from the thymus, whereas 20 injections gave rise to a new surge of proliferation and preparation or beginning of thymocyte migration from the thymus. It is concluded that prolonged injection of T-activin does not disturb the fluctuation pattern of thymus functioning but activates the transformation and migration of thymocytes.