Síndrome de Morris completo. Presentación de un caso / Complete Morris Syndrome. Case Presentation

RESUMEN El síndrome de insensibilidad a los andrógenos, síndrome de Morris o feminización testicular es un desorden en la diferenciación sexual, en el cual el individuo es fenotípicamente femenino, pero con caracteres genéticos de un hombre. Se presenta el caso de una escolar de 9 años de edad con hernia inguinal bilateral como forma de presentación del síndrome de Morris. Se valora en consulta y se constata la presencia de testes en el acto quirúrgico, corroborada mediante anatomía patológica. Se realizó cariotipo describiéndose cromosómicamente 46XY. En edad prepuberal se reevalúa con hernias inguinales bilaterales y genitales externos de apariencia femenina. Se comprueba mediante exámenes imagenológicos ausencia de cuerpo uterino y anejos, con presencia de vagina permeable hasta su tercio medio, que termina en un saco ciego en el interior de la pelvis, realizándose orquiectomía por mínimo acceso sin plastia vaginal. La aparición de hernia inguinal bilateral en la infancia fue la forma de presentación del síndrome de Morris en esta paciente. Se presenta el caso por lo poco frecuente de la aparición de esta entidad.

ABSTRACT Androgen insensitivity syndrome, Morris syndrome or testicular feminization is a disorder in sexual differentiation, in which the individual is phenotypically feminine, but with a man's genetic characteristics. The case of a 9-year-old schoolgirl with bilateral inguinal hernia is presented as a form of presentation of Morris syndrome. It is assessed in consultation confirming the presence of testicles in the surgery, corroborated by pathological anatomy. A karyotype was described describing chromosomally 46XY. In prepubertal age it is reevaluated with bilateral inguinal hernias and external genitals of female appearance. It is verified by imaging examinations, the absence of uterine body and annexes, with presence of permeable vagina until its middle third, which ends in a blind sac inside the pelvis, performing orchiectomy by minimal access without vaginoplasty. Bilateral inguinal hernia in childhood was the form of presentation of Morris syndrome in this patient. The case is presented due to the low frequency of occurrence of this condition.

Sexual determination and differentiation during embryonic and fetal development of New Zealand rabbit females / Determinación y diferenciación sexual durante el desarrollo embrionario y fetal de conejos hembras de Nueva Zelanda

The aim of this study was to know the embryonic and fetal development of the female rabbit genital system (Oryctolagus cuniculus), describing its main phases and the moment of sexual differentiation. Eleven pregnant New Zealand female rabbits were used in different gestational phases. The day of coitus was determined as day 0. For each stage a minimum of two animals was considered. The samples were obtained every two days from the ninth day post-coitus (dpc) until the 28th dpc. The gestational period was divided in two: animals with undifferentiated sex (group 1) and animals with differentiated sex (group 2). The ages of embryos and fetuses were estimated through the crown-rump method. Subsequently, embryos and fetuses were dissected, fixed and processed to be embedded in paraffin (Histosec). The histological analysis was performed on sections stained with hematoxylin and eosin. Immunohistochemical analysis to determine sexual differentiation was performed on samples from the 16th, 18th and 28th dpc. Desert Hedgehog (Dhh) and Indian Hedgehog (Ihh) primary antibodies, respectively, were used to identify cells of the male and female germinal epithelium. The immunohistochemical results showed that at the 16th dpc, female sexual differentiation was evident, since positive expression of the Ihh protein was observed. Sexual differentiation was obtained through histological analysis on the 18th dpc and through anatomical observation of the external genitalia on the 24th dpc. Knowing the characteristics of the embryonic and fetal development of the female rabbit genital system as well as the moment of sexual differentiation make it possible to establish bases for future research that address the physiology and pathology of these organs. Thus, any alteration in the chain of events of sexual determination and differentiation must search for an explanation from the knowledge of the possible normal mechanisms affected.

El objetivo de esta investigación fue conocer el desarrollo embrionario y fetal del sistema genital femenino de conejo (Oryctolagus cuniculus), describiendo sus principales fases y el momento de la diferenciación sexual. Se utilizaron 11 conejos hembras gestantes neozelandesas, en diferentes fases gestacionales. El día del coito se determinó como día 0. Para cada etapa fue considerado un mínimos de dos animales. Las muestras fueron obtenidas cada dos días, a partir del noveno día post-coito (dpc) hasta el 28 dpc. El periodo gestacional fue dividido en dos: animales con sexo indiferenciado (grupo 1) y, animales con sexo diferenciado (grupo 2). Las edades de los embriones y los fetos fueron estimadas a través del método de crown-rump. Posteriormente, embriones y fetos fueron disecados, fijados y procesados para su inclusión en parafina (Histosec). El análisis histológico se realizó en secciones teñidas con Hematoxilina y Eosina. El análisis inmunohistoquímico para determinar la diferenciación sexual fue realizado en muestras de 16, 18 y 28 dpc. Para identificar células del epitelio germinativo masculino y feminino se utilizaron los anticuerpos primarios Desert Hedgehog (Dhh) e Indian Hedgehog (Ihh), respectivamente. Los resultados inmunohistoquímicos mostraron que a los 16 dpc se evidenció diferenciación sexual femenina, ya que se observó expresión positiva de la proteína Ihh. La diferenciación sexual, a través del análisis histológico fue obtenida a los 18 dpc y a través de la observación anatómica de los genitales externos a los 24 dpc. Conocer las características del desarrollo embrionario y fetal del sistema genital femenino de conejo, así como, el momento de la diferenciación sexual, permiten sentar bases para futuras investigaciones que aborden la fisiología y patología de estos órganos. Así, cualquier alteración en la cadena de eventos de la determinación y diferenciación sexual deberá buscar una explicación a partir del conocimiento de los posibles mecanismos normales afectados.

Disorders of sex development and factors related to sexual differentiation / 国际儿科学杂志

Human sexual differentiation is mainly manifested in behavior and brain development,which embodied in gender identity,gender role,sexual orientation and cognitive ability. Patients with disorders of sex development who show abnormal sex behavior provide a unique perspective for the study of sexual differentia-tion. Studies have found the main factors that affect sexual differentiation including sex chromosomes,sex hor-mones and social psychological factors. The influencing degree of these three factors is different,and there are strong interactions within them. Moreover,the development of medical imageology has led to a better understand-ing of the sexual differences in brain structure and cognitive ability. At present,the studies of human sexual dif-ferentiation are scarce,and the objects of these studies mainly focus on patients with disorders of sex develop-ment. This paper reviews the recent studies on disorders of sex development and factors related to sexual differ-entiation.

Mutation analysis of NANOS3 in Brazilian women with primary ovarian failure

OBJECTIVES: Primary ovarian failure is a rare disorder, and approximately 90% of cases are of unknown etiology. The aim of this study was to search for mutations in NANOS3, a gene that was recently related to the etiology of primary ovarian failure, in a group of Brazilian women. METHODS: We screened for NANOS3 DNA variants in 30 consecutive women who were previously diagnosed with primary ovarian failure, of unknown etiology and compared the results with those from 185 women with normal fertility. The NANOS3 gene was amplified by polymerase chain reaction using pairs of specific primers and then sequenced. The resulting sequences were compared with control sequences available in the National Center for Biotechnology and Information database. RESULTS: No mutations in NANOS3 were found in primary ovarian failure patients, but four previously described polymorphisms were identified at a similar frequency in the control and primary ovarian failure groups. CONCLUSIONS: Mutations in NANOS3 were not associated with primary ovarian failure in the present cohort.

Clitoral Length and Anogenital Ratio in Indian Newborn Girls.

Objective: To generate normative data on clitoris length, anogenital distance and anogenital ratio in Indian newborns. Design: Cross-sectional study. Setting: Neonatal unit of a tertiary care teaching hospital in Kolkata. Participants: 378 female neonates, who were hemo-dynamically stable without critical illness or chromosomal anomaly, and without any vulval hematoma or genital abnormalities. Interventions: Measurements were recorded using a digital vernier caliper between 24-72 hours. Infant was held in position by an assistant, while the investigator measured clitoral length by gently retracting the labia majora. Anogenital distance (centre of the anus to posterior convergence of the fourchette) and anogenital ratio (anogenital distance divided by the distance from centre of the anus to base of the clitoris) was also measured. Main outcome measures: Gestational age- and birthweight-wise normative values of clitoral length, anogenital distance and anogenital ratios. Results: Mean clitoral length was 3.1 (1.54) mm for the whole cohort while anogenital distance and anogenital ratio were 10.2 (2.78) mm and 0.34 (0.07) mm, respectively. The gestation age-wise percentile charts of clitoral length, anogenital distance and anogenital ratio have been generated. There was no correlation between clitoral length and gestational age, body length, head circumference and birth weight. Correlations were also weak for anogenital distance. Conclusions: The normative values generated can serve as reference standard in the assessment of clitoromegaly, ambiguous genitalia, virilizing effects and suspected in utero androgen exposure.

Profile of patients with genitourinary anomalies treated in a clinical genetics service in the Brazilian unified health system / Perfil de pacientes com anormalidades geniturinárias atendidos em serviço de genética clínica no sistema único de saúde

To describe the profile of patients with genitourinary abnormalities treated at a tertiary hospital genetics service. Methods: Cross-sectional study of 1068 medical records of patients treated between April/2008 and August/2014. A total of 115 cases suggestive of genitourinary anomalies were selected, regardless of age. A standardized clinical protocol was used, as well as karyotype, hormone levels and genitourinary ultrasound for basic evaluation. Laparoscopy, gonadal biopsy and molecular studies were performed in specific cases. Patients with genitourinary malformations were classified as genitourinary anomalies (GUA), whereas the others, as Disorders of Sex Differentiation (DSD). Chi-square, Fisher and Kruskal–Wallis tests were used for statistical analysis and comparison between groups. Results: 80 subjects met the inclusion criteria, 91% with DSD and 9% with isolated/syndromic GUA. The age was younger in the GUA group (p<0.02), but these groups did not differ regarding external and internal genitalia, as well as karyotype. Karyotype 46,XY was verified in 55% and chromosomal aberrations in 17.5% of cases. Ambiguous genitalia occurred in 45%, predominantly in 46,XX patients (p<0.006). Disorders of Gonadal Differentiation accounted for 25% and congenital adrenal hyperplasia, for 17.5% of the sample. Consanguinity occurred in 16%, recurrence in 12%, lack of birth certificate in 20% and interrupted follow-up in 31% of cases. Conclusions: Patients with DSD predominated. Ambiguous genitalia and abnormal sexual differentiation were more frequent among infants and prepubertal individuals. Congenital adrenal hyperplasia was the most prevalent nosology. Younger patients were more common in the GUA group. Abandonment and lower frequency of birth certificate occurred in patients with ambiguous or malformed genitalia. These characteristics corroborate the literature and show the biopsychosocial impact of genitourinary anomalies.

Descrever o perfil de pacientes com anormalidades geniturinárias atendidos em serviço de genética de hospital terciário. Métodos: Estudo transversal de 1.068 prontuários de pacientes atendidos entre abril/2008 e agosto/2014. Foram selecionados 115 casos sugestivos de anomalias geniturinárias, independentemente da idade. Usaram-se protocolo clínico padronizado, cariótipo, hormônios e ultrassonografia geniturinária para avaliação básica. Laparoscopia, biopsia gonadal e estudos moleculares foram feitos em casos específicos. Pacientes com malformações geniturinárias foram classificados como defeitos geniturinários (DGU), os demais, como distúrbios da diferenciação do sexo (DDS). Usaram-se qui-quadrado, Fisher e Kruskal-Wallis para análise estatística e comparação entre os grupos. Resultados: Preencheram os critérios de inclusão 80 sujeitos, 91% com DDS e 9% com DGU isolados/sindrômicos. A idade foi menor no grupo DGU (p<0,02), mas esses grupos não diferiram quanto a genitália externa, interna e cariótipo. Verificou-se cariótipo 46,XY em 55% e aberrações cromossômicas em 17,5% dos casos. Ambiguidade genital ocorreu em 45%, predominou em pacientes 46,XX (p<0,006). Distúrbios da diferenciação gonadal representaram 25% e hiperplasia adrenal congênita; 17,5% da amostra. Consanguinidade ocorreu em 16%, recorrência em 12%, ausência de registro civil em 20% e interrupção do seguimento em 31% dos casos. Conclusões: Predominaram pacientes com DDS. Ambiguidade genital e diferenciação sexual anômala foram mais frequentes entre recém-nascidos e pré-púberes. Hiperplasia adrenal congênita foi a nosologia mais prevalente. Pacientes mais jovens pertenciam ao grupo DGU. Menor frequência de registro civil e abandono ocorreram em pacientes com genitália ambígua ou malformada. Essas características corroboram a literatura e evidenciam o impacto biopsicossocial das anormalidades geniturinárias.

Alteraciones de la diferenciación sexual en pacientes de las regiones Capital y centro occidental de Venezuela / Disorders of sexual differentiation in patiens from the capital and west Center Regions of Venezuela

Las alteraciones de la diferenciación sexual (ADS) son patologías originadas por trastornos en una de las tres etapas sucesivas de dicha diferenciación: cromosómica (XX, XY), gonadal (testículo, ovario) o fenotípica. El objetivo del trabajo fue dar a conocer la forma de presentación de las ADS en pacientes provenientes de las regiones Capital y Centro Occidental de Venezuela. Se incluyeron diecisiete pacientes y se elaboraron los árboles genealógicos, se realizó evaluación clínica, estudios hormonales, citogenéticos, imagenología y determinación de marcadores del gen SRY y microsatélites del cromosoma Y. En función de la evaluación clínica y los datos obtenidos de los exámenes practicados, se efectuaron los diagnósticos siguientes: a) Doce corresponden a ADS 46,XX , de los cuales siete pacientes tienen ADS por exceso de andrógenos, un caso con reversión sexual, un ADS ovotesticular, un caso con síndrome malformativo, uno con disgenesia gonadal y uno con hipogonadismo, b) Cuatro presentan ADS 46,XY (un paciente con síndrome de Smith-Lemli-Opitz II, uno con síndrome malformativo y dos casos con hipogonadísmo), c) Un caso de ADS por alteración cromosómica 46,XXY (síndrome de Klinefelter). En relación a la edad de la primera consulta, la mayor parte (47,1%) se realizó en menores de 5 años, referidos por ambigüedad sexual con necesidad de resolver la identificación del sexo; en la pubertad los pacientes consultan por alteraciones en los caracteres sexuales secundarios y amenorrea (adolescentes); en la adultez por infertilidad. Los resultados permitieron realizar un mejor asesoramiento genético y contribuir a mejorar la calidad de vida de los pacientes y sus grupos familiares.

Disorders of sexual differentiation (DSD) are pathologies characterized by an atypical development of chromosomal (XX, XY) gonadal (testis, ovary) or phenotypical sex. The objective of this work was to inform the presentation forms of SDS in patients from the Capital and West Center regions of Venezuela. Seventeen patients were included and the pedigrees, clinical evaluation, hormonal studies, cytogenetic, imaging and identification of SRY gene markers and Y chromosome microsatellites were made. Depending on the clinical evaluation and data from examinations carried out, the following diagnoses were made: a)Twelve patients correspond to DSD 46, XX, of which seven patients have DSD by androgen excess, a case with sex reversal a ovotesticular DSD, a case with malformation syndrome, one with gonadal dysgenesis and one hypogonadism; b) Four patients presented DSD 46, XY (a patient with Smith-Lemli-Opitz syndrome II, one malformation syndrome and two cases with hypogonadism) c) A case of ADSs by chromosomal abnormality 46,XXY (Klinefelter syndrome). In relation to age of first consultation, the majority (47.1%) was performed in children under 5 years, referred by sexual ambiguity with need to address sex identification. In puberty, the patients consult due to alterations in secondary sexual characteristics and amenorrhea in teenagers, in adulthood due to infertility. The results helped to make a better genetic counseling and to improve the quality of life of patients and their families.

Intrauterine sexual differentiation: biosyntesis and action of sexual steroid hormones

The objective of this review was to describe sexual differentiation events in mammals, relating them to biosynthesis of sexual steroid hormones and their mechanisms of action. Cholesterol is the precursor of sexual steroid hormone biosynthesis via action of several enzymes converting these hormones. Progestagens hormones serve as substrate for the production of androgens, which in turn serve as substrate for estrogen hormones. These hormones are responsible for sexual differentiation and reproductive cycles of mammals. Sexual differentiation process comprises determining the sexual chromosomes XX or XY + SRY and other genes linked to them, differentiation of gonads in testis or ovary, differentiation of internal and external male or female genital organs from undifferentiated anatomical structures present in the embryo, which is dependent on the presence or absence of testes and the production of anti-Müllerian hormone and testosterone; and secondary sexual differentiation, which is the response of various tissues to hormones produced by the gonads, interacting with genes linked to sexual chromosomes to increase or decrease the differences in sexual phenotype. However, some differences between the sexes and some anomalies of sexual differentiation are not explained only by these sexual hormonal effects, but also by the effect of genes encoded in sexual chromosomes.

Hiperplasia adrenal congénita en forma clásica virilizante simple / Congenital adrenal hyperplasia in simple classical virilizing form

El déficit de 21-hidroxilasa es la forma más frecuente de hiperplasia adrenal congénita, que forma parte de los desórdenes de la diferenciación sexual. Se presentan 3 casos. El primero, un recién nacido de 19 días que es llevado a consulta por presentar desórdenes de los genitales externos. Al examen físico presentaba un clítoris aumentado de tamaño, con orificio uretral en su base y engrosamiento de los rodetes labioescrotales. El diagnóstico se realizó por ultrasonido ginecológico, cromatina sexual, estudios hormonales y cariotipo. El segundo caso, un recién nacido de 15 días que también es llevado a consulta por desórdenes de los genitales externos, con examen físico similar al primer caso, y se le realizaron los mismos complementarios para su diagnóstico. El tercer caso, un lactante de 2 meses de edad, que es llevado a consulta por igual motivo, y que al examen físico se encontró hiperplasia del clítoris, con orificio en su base, y engrosamiento de los labios mayores que estaban fusionados en la línea media. Se le indicaron iguales complementarios. Se diagnosticó en los 3 casos una hiperplasia adrenal virilizante, y se realizó tratamiento sustitutivo hormonal y cirugía reconstructiva de los genitales externos.

Steroid 21-hydroxylase is the most frequent form of congenital adrenal hyperplasia that is part of the sexual differentiation disorders. This article reported 3 cases. The first one was a 19 days-old infant who was taken to the doctor´s because of external genitalia disorders. The physical exam revealed augmented clitoris with urethral orifice in its basis and thickening of the labioscrotal swellings. The patient was diagnosed by means of gynecological ultrasound, sexual chromatin, hormonal studies and karyotype. The second case was a 15 days-old newborn, who was also taken to the doctor´s for external genitalia disorders. The physical exam was similar to that of the first case and the same complementary tests were performed for diagnosis. The third case was a 2 months-old infant who was taken to the medical service for the same reasons, and his physical exam showed clitoris hyperplasia, orifice in its base and thickening of labia majora that fused in the midline. The same complementary tests were indicated. The final diagnosis in these three cases was virilizing adrenal hyperplasia. They were all treated with hormone replacement therapy and reconstructive surgery of their external genitalia.

Manejo de la hiperplasia suprarrenal congénita

La hiperplasia adrenal congénita (HSC) es un grupo de desórdenes causados por defectos en la esteroidogénesis adrenal. En su forma más común, la deficiencia de la enzima 21-α-hidroxilasa, los pacientes desarrollan grados variables de deficiencia de glucocorticoides y mineralocorticoides, así como de exceso de andrógenos. En general se clasifica en formas clásicas y no clásicas. Los objetivos del tratamiento son sustituir la deficiencia de cortisol y aldosterona, evitar el hiperandrogenismo y lograr la mejor talla final; aunque estos objetivos parecen bastante sencillos, en la práctica, son muy difíciles de lograr. La terapia con glucocorticoides y mineralocorticoides es guiada por el monitoreo de variables clínicas y de concentraciones de hormonas androgénicas y electrolitos. Con respecto al crecimiento, se debe mantener un delicado equilibrio; el sobretratamiento con glucocorticoides puede conducir a deterioro del mismo, y un tratamiento insuficiente, al exceso de andrógenos y maduración epifisaria prematura. Se presenta el protocolo de diagnóstico y tratamiento de la HSC de la Unidad de Endocrinología del Instituto Autónomo Hospital Universitario de Los Andes, Mérida, Venezuela.

Congenital adrenal hyperplasia (CAH) is a group of disorders caused by defects in the adrenal steroidogenic pathways. In its most common form, 21-α-hydroxylase deficiency, patients develop varying degrees of glucocorticoid and mineralocorticoid deficiency as well as androgen excess. It is generally classified as classical and non-classical forms. The goals of treatment are to replace the cortisol and aldosterone deficiency, avoid hyperandrogenism and achieve the best final height. Although these goals seem pretty straightforward, in practice, they are very difficult to achieve. Glucocorticoid and mineralocorticoid therapy is guided by monitoring clinical parameters as well as adrenal hormone and electrolytes concentrations. Practitioners must strike a fine balance; on height, overtreatment with glucocorticoids can lead to poor growth, and undertreatment, to androgen excess and premature epiphyseal maturation. The CAH diagnosis and treatment of the Endocrinology Service, Autonomous Institute University Hospital of The Andes, Mérida, Venezuela.

Effects of delayed sowing-date on yield components of Thladiantha setispina / 中草药

Objective: In order to discuss the influence difference of environmental stress on dioecious plants and the response of environmental factors influence on the fruiting and yield of Thladiantha setispina. Methods: The effects of the different sowing-dates on the female plant rate, fruit character, and seed yield of T. setispina were investigated by the comparative ways. Results: Different sowing-dates on differentiation of male and female plants had a significant impact. The appropriate delay of sowing-date could significantly improve the proportion of female T. setispina (P 0.05), but the sowing-date on yield components of T. setispina had a direct impact on related indicators, yield differences during the treatments reached a very significant level (P < 0.01). Conclusion: The appropriate delaying of sowing-date could help to improve the seed production of T. setispina.

Environmental endocrine disruptors and abnormalities of sexual differentiation and sexual development inchildren / 国际儿科学杂志

Environmental endocrine disruptors are pollutants of many exogenous chemical classes,which are ubiquitous and persistent in the environment and can interfere with the body 's natural steroidogenesis,secretion,transport,and receptor binding,biotransformation and removal of other aspects,thus,they may disturb normal hormone maintaining the organism 's balance and regulating development process.Therefore,exposure to these pollutants is one of the biggest factors that induce sex differentiation and sexual abnormality in children,which has been proved by many data from epidemiological researches.Environmental endocrine disruptors may influence the sexual differentiation and sexual development process of children by disturbing the hypothalamus-pituitary-gonadal axis and affecting the biosynthesis,transport,receptor binding,metabolism and clearance of androgen as well as interacting with genes.

Varón 46 XX, un desorden del desarrollo sexual testicular: a propósito de un caso clínico / 46 XX disturbance of testicular sexual development: report of one case

We report a previously healthy child that consulted for the first time at the age of 11 years for short stature. At that moment, his height was 138 cm, with a mid-parental target height of 175 cm. He was in an initial pubertal stage with a Tanner II pubic hair and a testicular volume of 4 ml. Initial laboratory examination was normal and the child had a concordant bone age. He consulted again at 16 years of age, with a height of 162.4 cm (percentile 5 for age), a bone age of 18 years and a Tanner IV pubic hair, but the testicular volume persisted at 4 ml. A genetic study disclosed a 46 XX karyogram and a fluorescence in situ hybridization (FISH) for chromosomes X and Y that showed a positive sex determining region Y (SRY) in X chromosome.

Atresia anal, fístula uretrorretal congênita, bolsa escrotal acessória e pseudo-hermafroditismo em bezerro mestiço / Anal atresia, congenital urethrorectal fistula, accessory scrotum and pseudohermafroditism in a crossbred calf

Neste trabalho, é descrito o caso de um bezerro mestiço recém-nascido que apresentava atresia anal tipo 2, fístula uretrorretal congênita, bolsa escrotal bífida e pseudo-hermafroditismo masculino. O principal sinal clínico era a eliminação de fezes por meio do óstio prepucial, uma apresentação incomum em casos de fístula uretrorretal em animais machos. Apesar de o quadro de atresia anal ser relativamente comum nessa espécie, os outros defeitos congênitos encontrados são pouco frequentes.

In this study, the case of a newborn calf, which presented type 2 anal atresia, congenital urethrorectal fistula, bifid scrotum and male pseudohermafroditism is described. The main clinical sign was the elimination of feces by the prepucial ostium, an unusual finding in cases of urethrorectal fistula in male animals. Although anal atresia is relatively common in bovines, the other congenital defects found in this case are uncommon.

Perfil clínico de 62 casos de distúrbios da diferenciação sexual / Clinical profile of 62 cases of sexual differentiation disorders

Objetivo: Descrever o perfil clínico dos casos de distúrbios da diferenciação sexual em acompanhamento no Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, no Rio de Janeiro, nos últimos cinco anos.Métodos: Revisão dos prontuários dos pacientes, com o diagnóstico de genitália ambígua em acompanhamento nos últimos cinco anos, segundo os critérios clínicos descritos por Danish, em 1982. O registro mais antigo foi feito em 1981 e o mais recente de junho de 2006. Resultados: Foram encontrados 62 casos de genitália ambígua: 26 com registro do sexo feminino e 36 com registro do sexo masculino. O diagnóstico mais freqüente foi o de hiperplasia congênita de supra-renal (33,9%), seguido de quadros sindrômicos (14,5%) e disgenesias gonadais (9,7%). A média de idade ao diagnóstico foi de 7,2 anos (de zero a 42 anos). Conclusões: A ambigüidade genital não é uma doença específica, mas um conjunto de alterações que direcionam o clínico a buscar diagnósticos específicos. A freqüência dessa afecção depende dos critérios diagnósticos utilizados. A adoção de critérios amplos aumenta a chance de detecção precoce do quadro bem como de cuidado adequado a crianças com distúrbios da diferenciação sexual.

Objective: To report patients with ambiguous genitalia assisted at the State Institute of Diabetes and Endocrinology of Rio de Janeiro, Brazil, in the last five years.Methods: Retrospective chart review of all cases of ambiguous genitalia, classified according to Danish criteria (1982), who attended follow-up visits in the last five years. The oldest record is from 1981 and the most recent one, 2006. Results: 62 patients with ambiguous genitalia were found: 26 of them assigned as females and 36 as males. The most frequent diagnosis was congenital adrenal hyperplasia (33.9%), followed by syndromic diseases (14.5%) and gonadal dysgenesis (9.7%). The majority of patients with ambiguous genitalia were detected at birth, however, the mean age at the diagnosis was 7.2 years (zero to 42 years).Conclusions: Genital ambiguity is not a specific disease, but a set of problems that directs the physician to search specific diagnosis. The frequency of this condition depends on the diagnostic criteria used. Adopting amplified criteria in order to diagnose genital ambiguity will increase the possibility of early detention and adequate handling of these patients.

Amenorréia primária e cariótipo XY: identificando pacientes em risco / Primary amenorrhea and XY karyotype: identifying patients in risk

OBJETIVO: verificar a prevalência e as características clínicas de pacientes com amenorréia primária e cariótipo XY avaliadas em nosso Serviço com o intuito de identificar achados que possam auxiliar em seu reconhecimento. MÉTODOS: no período de Janeiro de 1975 a Novembro de 2007, foram avaliadas 104 pacientes com amenorréia primária. Para todos os casos foi realizada a análise pelo cariótipo por bandas GTG. Destas, 21 (20,2%) apresentavam uma constituição 46,XY. Contudo, duas foram excluídas do estudo por terem prontuários incompletos. Das 19 pacientes que compuseram a amostra, a maior parte veio encaminhada pela ginecologia (63,2%). Suas idades variaram entre 16 e 41 anos (média de 22,1 anos). Realizou-se uma coleta de dados sobre sua história familiar e pregressa, exame físico e resultados de exames complementares. Para determinação dos seus diagnósticos levaram-se em consideração essas informações. RESULTADOS: a síndrome de resistência aos androgênios foi o diagnóstico predominante (n=12; 63,2%). Cinco pacientes (26,3%) apresentavam disgenesia gonadal pura XY (DGP XY), uma (5,3%) deficiência de 17-alfa hidroxilase e uma (5,3%) deficiência de 5-alfa redutase. Achados clínicos freqüentemente observados nessas pacientes incluíram desenvolvimento anormal dos caracteres sexuais secundários (n=19), agenesia uterina com vagina em fundo de saco (n=14), história familiar de amenorréia (n=8) e gônadas palpáveis no canal inguinal (n=5). Duas delas apresentavam história de hérnia inguinal. Hipertensão arterial sistêmica foi diagnosticada somente na paciente com deficiência de 17-alfa hidroxilase, e malignização gonadal, naquela com DGP XY. CONCLUSÕES: a freqüência de pacientes com cariótipo XY (20%) foi superior à usualmente descrita na literatura (3 a 11%). Acreditamos que isso tenha relação com a forma de encaminhamento das pacientes ao Serviço...

PURPOSE: to verify the prevalence and clinical characteristics of patients with primary amenorrhea and XY caryotype, evaluated in our Service, aiming at identifying findings which could help their recognition. METHODS: from January 1975 to November 2007, 104 patients with amenorrhea were evaluated. All the cases were analyzed by the caryotype by GTG bands. Among them, 21 (20.2%) presented a XY 46 constitution. Nevertheless, two of them were excluded from the study, because of incomplete data in their patient's chart. Most of the 19 patients who formed the sample had been referred to us by the gynecology clinics (63.2%). Their ages varied from 16 to 41 years old (an average of 22.1). Data were collected about their family and previous history, physical examination and results of complementary exams and the information was taken into consideration to determine the diagnosis. RESULTS: the predominant diagnosis was resistance to androgens syndrome (n=12; 63.2%); five patients (25.3%) presented XY pure gonadal dysgenesis (XY PGD), one (5.3%) 17 alpha-hydroxylase deficiency, and one (5.3%), 5 alpha-reductase deficiency. Clinical findings frequently found in these patients included abnormal development of secondary sexual characters (n=19), uterine agenesia with a blind vagina (n=14), family history of amenorrhea (n=8), and palpable gonads in the inguinal canal (n=5). Two of them presented a history of inguinal hernia. Systemic arterial hypertension was only diagnosed in the patient with 17 alpha-hydroxylase deficiency, and gonadal malignization, in the one with XY PGD. CONCLUSIONS: the rate of patients with XY caryotype (20%) was higher than the one described in the literature (3 to 11%). It is believed that this fact is related to the way patients are usually referred to our service. Some findings from the clinical history and from the physical examination should be evaluated as a routine in individuals with primary amenorrhea...

Diferenciación sexual en la langosta de agua dulce Cherax quadricarinatus (Decapoda: Parastacidae) / Sexual differentiation in the freshwater crayfish Cherax quadricarinatus (Decapoda: Parastacidae)

Determinamos el momento del desarrollo postembrionario en que se produce la diferenciación sexual primaria en la langosta Cherax quadricarinatus. Esta es evidenciada por la presencia de las gónadas y sus respectivos conductos. También determinamos la diferenciación sexual definida por la aparición de los caracteres sexualessecundarios. Se observaron 797 machos, 506 hembras y 456 individuos intersexos de 0.02 a 89.96 g (de criadero y laboratorio). Disecamos una submuestra de 106 machos, 69 hembras y 59 individuos intersexos para la caracterización macroscópica de la estructura gonadal. La diferenciación de los gonoporos se inicia aproximadamente a los 0.10 g, en sincronía con la diferenciación del sistema reproductor en machos, hembras e intersexos. La adquisición de la forma definitiva de ovario, oviducto, testículo y vaso deferente son posteriores. El appendix masculina iniciasu diferenciación a los 0.12-0.2 g y adquiere los rasgos característicos del appendix de los adultos a partir de 1-2 g.La diferenciación de la mancha roja (red patch) ocurre a partir de los 2.3 g.

We determined the earliest stage of postembryonic development at which primary and secondary sexual differentiations occur in the freshwater (“red claw”) crayfish Cherax quadricarinatus. For this purpose,797 males, 506 females and 456 intersex specimens within a weight range of 0.02-89.96 g were observed under stereoscopic microscope to determine the presence of the genital openings at the basis of the third (females) or fifth (males) pair of pereiopods. Animals presenting both pairs of genital openings were considered as intersex. A subsample of 106 males, 69 females and 59 intersex were dissected for the macroscopic characterization of gonad morphology. The development of the genital openings began approximately at 0.10 g, simultaneously with the differentiation of the reproductive system in females, males and intersex. Although the differentiation of the reproductive system started very early in the postembryonic development, the definitive form and colour of ovaries, oviducts, testes and vasa deferentia was acquired later. The differentiation of the appendix masculina began at 0.12-0.2 g and acquired the elongated shape of the adult at 1-2 g. The soft red patch characteristic of adult males started at 2.3 g of body weight in both chelipeds.

SRY Gene Evaluation in Patients with the Disorders of Sexual Differentiation / 대한비뇨기과학회지

The disorders of sexual differentiation occurred due to the incompatibility of chromosomal sex, gonadal sex and phenotypic sex. A gene within Y chromosome such as SRY gene has been searched to explain this phenomenon. We report cases of defective sexual differentiation, where it is difficult to diagnose with Giemsa stain of Y chromosome alone but SRY gene evaluation was helpful in the diagnosis and treatment of these cases. Genomic DNA from WBC was extracted. XES 10 and XES 11 were used as primers in separately SRY gene by electrophoresis. A positive SRY gene facilitated in confirming the diagnosis of the following cases: Klinefelter`s syndrome with a positive SRY gene originally diagnosed as 46 XX male, Klinefelter`s syndrome with 46XX,a positive SRY gene that was thought to be chordee without hypospadias. Turner`s syndrome that was difficult to be diagnosed due to 46XY, a positive SRY gene, however, SRY gene detection was helpful to detect germ cell tumor development early. 46XX hermaphroditism without SRY gene was diagnosed as true intersex after pathologic examination. Two cases of 46XY hermaphroditism with SRY gene were diagnosed finally as 46 XY true intersex and mixed gonadal dysgenesis each other. Congenital adrenal hyperplasia and androgen receptor defect were confirmed by traditional methods such as hormonal tests and radiologic findings. SRY gene evaluation facilitated in identifying the pathophysiology of many defective sexual differentiations, however, this alone had a limit to explain all these cases. So future research into genes in the autosome, sex chromosome and Z protein will help in the diagnosis and treatment of patients with the disorders of sexual differentiation.

Analysis of SRY Gene in Korean Patients with Swyer Syndrome and their Family Members / 대한산부인과학회잡지

Individuals affected with Swyer syndrome are phenotypic females with 46, XY karyotype, sexual infantilism, mullerina derivatives, and bilateral streak gonads that may undergo neoplastic transformation. The pathogenesis of this syndrome is uncertain, but may be related to a defect in the regulation or expression of the testicular determining factor which is believed to be located on the short arm of the Y chromosome. Recently, a region termed "SRY", a single copy gene of the Y chromosome was identified as belonging to a testis-determining gene. This gene is Y-specific, highly conserved among mammals, and transcribed only in testis. The predicted amino acid sequence of SRY shares homology with DNA-binding domains of transcription factors such as chromatinassociated, nonhistone proteins HMG 1 and HMG 2. Hence, it was thought that there may be some change in SRY gene of the patients with Swyer syndrome. And it was reported in some cases that there was deletion or mutation in the gene, but no abnormality of SRY gene was observed in other cases. So, it is a new approach to understand the mechanism of the human sexual differentiation to investigate this syndrome in terms of DNA sequence of SRY gene. To verify the presence or absence of SRY, or the change in SRY, we performed polymerase chain reaction and DNA sequencing of the conserved region of SRY gene from four patients with Swyer syndrome and their family members. The results are as follows. 1) Four patients with Swyer syndrome, their father, and two normal male control were positive whereas two female control were negative for the band that represents the coding sequence of SRY. 2) The DNA sequences of SRY gene from four patients with Swyer syndrome, their father, and two normal male control were the same, and there was no deletion or mutation in the gene. In conclusion, there may be complex sex determining cascade including other genes not only on the Y chromosome, but also on the X chromosome or even autosome in human sexual differentiation.

A Clinical Observatien on 60 Cases of Disorders of Sexual Differentiation / 대한비뇨기과학회지

From the stand point of understanding the pathophysiology of abnormalities in sexual development, disorders can be categorized as resulting from derangements in any of the 3 principal processes involved in sexual differentiation, namely, disorders of genetic sex, disorders of gonadal sex, and disorders of phenotypic sex. During the last 5 years we have found 60 cases of disorders of sexual differentiation and tried to classify the cases according to the schematization of the above. The cases were reviewed with the observation on karyotype, external or internal or internal genitalia, in some, hormonal balance, utilizing various methods of operative examination The disorders of genetic sex consist of 3 cases of true hermaphroditism, 7 cases of Klinefelter`s syndrome, 9 cases of Turner`s syndrome, 1 case of sex reversal syndrome (XX male) l case of mixed gonadal dysgenesis, and l case of dysgenetic male pseudohermaphroditism. The disorders of gonadal sex consist of 6 cases of pure gonadal dysgenesis. The disorders of phenotypic sex consist of 11 cases of adrenogenital syndrome, 7 cases of male pseudohermaphroJitism, and 2 case of congenital absence of vagina. The remained 12 cases which were suspected as disorders of sexual differentiation were not able to be differentiated according to the inadequacy of diagnostic studies.