ABSTRACT
Introducción. La pubertad se manifiesta inicialmente por la aparición de los caracteres sexuales secundarios, como consecuencia de cambios hormonales que progresivamente conducen a la madurez sexual completa. En Argentina y el mundo, la pandemia ocasionada por el coronavirus SARS-CoV-2 generó un confinamiento que pudo haber interferido en el inicio y tempo del desarrollo puberal. Objetivo. Describir la percepción de los endocrinólogos pediatras del país sobre las consultas por sospecha de pubertad precoz y/o pubertad de rápida progresión durante la pandemia. Materiales y métodos. Estudio descriptivo, observacional, transversal. Encuesta anónima a endocrinólogos pediatras pertenecientes a la Sociedad Argentina de Pediatría y/o a la Asociación de Endocrinología Pediátrica Argentina, en diciembre de 2021. Resultados. Respondieron la encuesta 83 de 144 endocrinólogos pediátricos (tasa de respuesta 58 %). Todos consideraron que aumentó la consulta por desarrollo precoz o temprano, ya sea en sus variantes telarca precoz (84 %), pubarca precoz (26 %) y/o pubertad precoz (95 %). El 99 % acuerda con que se ha dado en mayor medida en niñas. La totalidad de los encuestados también considera que aumentó el diagnóstico de pubertad precoz central. El 96,4 % considera que ha aumentado el número de pacientes tratados con análogos de GnRH. Conclusión. Nuestros resultados sobre la percepción de endocrinólogos pediatras coinciden con datos publicados en otras regiones sobre el aumento del diagnóstico de pubertad precoz durante la pandemia por COVID-19. Se reafirma la necesidad de generar registros nacionales de pubertad precoz central, difundir las evidencias para su detección y abordaje oportuno.
Introduction. Puberty is manifested initially by the onset of secondary sexual characteristics as a result of hormonal changes that progressively lead to complete sexual maturity. In Argentina and worldwide, the lockdown resulting from the SARS-CoV-2 pandemic may have interfered in the onset and timing of pubertal development. Objective. To describe the perception of pediatric endocrinologists in Argentina regarding consultations for suspected precocious and/or rapidly progressive puberty during the pandemic. Materials and methods. Descriptive, observational, cross-sectional study. Anonymous survey among pediatric endocrinologists members of the Sociedad Argentina de Pediatría and/or the Asociación de Endocrinología Pediátrica Argentina administered in December 2021. Results. Out of 144 pediatric endocrinologists, 83 completed the survey (rate of response: 58%). All of them considered that consultation for precocious or early puberty increased, either in terms of early thelarche (84%), early pubarche (26%), and/or precocious puberty (95%). Ninety-nine percent agreed that this has occurred to a greater extent in girls. All survey respondents also consider that the diagnosis of central precocious puberty has increased. In total, 96.4% of respondents consider that the number of patients treated with GnRH analogs has increased. Conclusion. Our results about the perception of pediatric endocrinologists are consistent with data published in other regions on the increase in the diagnosis of precocious puberty during the COVID-19 pandemic. We underscore the need to develop national registries of central precocious puberty, and to disseminate the evidence for a timely detection and management
Subject(s)
Humans , Child , Puberty, Precocious/diagnosis , Puberty, Precocious/epidemiology , COVID-19/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Pandemics , Endocrinologists , SARS-CoV-2ABSTRACT
As diferenças ou distúrbios do desenvolvimento sexual (DDS) compreendem um grupo heterogêneo de condições congênitas que resultam na discordância entre os cromossomos sexuais, as gônadas e/ou o sexo anatômico de um indivíduo. A classificação desses distúrbios é baseada no cariótipo conforme o Consenso de Chicago de 2006 e substitui os termos pseudo-hermafroditismo, hermafroditismo e intersexo. O objetivo desta revisão é fornecer ao ginecologista conhecimentos básicos sobre a etiologia, fisiopatologia e orientações das principais anormalidades de DDS para uma avaliação diagnóstica e terapêutica no atendimento de mulheres na infância, adolescência e em idade adulta com cariótipo 46,XY. O diagnóstico deve ser realizado pela interação entre o exame clínico as dosagens hormonais, os exames de imagem e a análise genética, desde o cariótipo até o estudo de alterações dos genes por técnicas de biologia molecular. O tratamento é realizado de acordo com a etiologia e inclui intervenções cirúrgicas como a gonadectomia e plásticas sobre a genitália externa, terapia de reposição hormonal e apoio psicológico. São necessárias a individualização dos casos e uma equipe interdisciplinar, para um atendimento adequado às mulheres com cariótipo 46,XY.(AU)
Differences or disorders of sexual development (DSDs) comprise a heterogeneous group of congenital conditions that result in the disagreement between an individual's sex chromosomes, gonads and/or anatomic sex. The classification of these disorders is based on the karyotype according to the 2006 Chicago Consensus and replaces the terms pseudohermaphroditism, hermaphroditism and intersex. The aim of this review is to provide the gynecologist with basic knowledge about the etiology, pathophysiology and guidelines of the main abnormalities of DDS for a diagnostic and therapeutic evaluation in the care of women in childhood, adolescence and adulthood with a karyotype 46,XY. The diagnosis must be made by the interaction between clinical examination hormonal measurements, imaging and genetic analysis from the karyotype to the study of gene alterations by molecular biology techniques. Treatment is carried out according to the etiology and includes surgical interventions such as gonadectomy and plastic surgery on the external genitalia, hormone replacement therapy and psychological support. Individualization of cases and an interdisciplinary team are required to provide adequate care for women 46,XY karyotype.(AU)
Subject(s)
Humans , Female , Disorder of Sex Development, 46,XY , Androgen-Insensitivity Syndrome , Estrogen Replacement Therapy , Cholestenone 5 alpha-Reductase/deficiency , Disorder of Sex Development, 46,XY/diagnosis , Disorder of Sex Development, 46,XY/etiology , Disorder of Sex Development, 46,XY/physiopathology , Disorder of Sex Development, 46,XY/therapyABSTRACT
Abstract With the widespread uptake of noninvasive prenatal testing (NIPT), a larger cohort of women has access to fetal chromosomal sex, which increases the potential to identify prenatal sex discordance. The prenatal diagnosis of androgen insensitivity syndrome (AIS) is an incidental and rare finding. We wish to present the diagnosis of a prenatal index case after NIPT of cell-free fetal DNA and mismatch between fetal sex and ultrasound phenotype. In this particular case, the molecular analysis of the androgen receptor (AR) gene showed the presence of a pathogenic mutation, not previously reported, consistent with complete androgen insensitivity syndrome. Carrier testing for the mother revealed the presence of the same variant, confirming maternal hemizygous inheritance. Identification of the molecular basis of these genetic conditions enables the preimplantation or prenatal diagnosis in future pregnancies.
Resumo Com a utilização generalizada de testes pré-natais não invasivos (TPNIs), uma crescente porção de mulheres tem acesso ao sexo cromossômico fetal, o que aumenta o potencial para identificar discordância sexual pré-natal. O diagnóstico pré-natal da síndrome de insensibilidade androgénica é um achado incidental e raro. Pretendemos apresentar um caso índice de diagnóstico pré-natal por meio de DNA fetal livre e incompatibilidade entre sexo fetal e fenótipo ecográfico. Neste caso particular, a análise molecular do gene do receptor de andrógenios (RA) revelou a presença de uma mutação patogênica, não relatada anteriormente, consistente com a síndrome de insensibilidade completa aos androgênios. A mãe revelou ser portadora da mesma variante, confirmando a hereditariedade hemizigótica. A identificação da base genética permite o diagnóstico pré-implantação ou pré-natal em futuras gestações.
Subject(s)
Humans , Male , Female , Pregnancy , Androgen-Insensitivity Syndrome/diagnosis , Androgen-Insensitivity Syndrome/genetics , Phenotype , Prenatal Diagnosis , Ultrasonography , MutationABSTRACT
Resumen: El trastorno del desarrollo sexual (TDS) testicular XX es una patología que se presenta en un individuo con cariotipo 46,XX con un fenotipo anatómico de genitales externos masculinos, que pueden variar desde la normalidad hasta la ambigüedad genital. Clínicamente se han descrito dos subgrupos de hombres 46,XX con SRY-negativos y SRY-positivos, dependiendo de la presencia o no del gen SRY que normalmente se encuentra en el cromosoma Y participando en la determinación testicular. En este artículo se describen los antecedentes personales y los hallazgos clínicos de un infante con anomalías del meato urinario en el cual se identificó un complemento cromosómico 46,XX. También, se realizó hibridación in situ fluorescente en linfocitos de sangre periférica que demostró la ausencia del gen SRY y confirmó la presencia de dos cromosomas X.
Abstract XX testicular disorder of sex development (DSD) is a pathology that occurs in an individual with a 46,XX karyotype and an anatomical phenotype of male external genitalia, which may vary from normal to ambiguous. Clinically, two subgroups of SRY-negative and SRY-positive, 46, XX men have been described, depending on the presence of the SRY gene that is normally found on the Y chromosome participating in testicular determination. This article describes the personal history and clinical findings of an infant with urethral meatus abnormalities in whom a 46,XX chromosome set was identified. Also, fluorescent in situ hybridization was performed in peripheral blood lymphocytes which demonstrated the absence of the SRY gene and confirmed the presence of two X chromosomes.
Resumo: O transtorno do desenvolvimento sexual (TDS) testicular XX é uma patologia apresentada em um indivíduo com cariótipo 46,XX com um fenótipo anatômico de genitais externos masculinos, que podem variar da normalidade à ambiguidade genital. Clinicamente, são descritos dois subgrupos de homens 46,XX com SRY-negativos e SRY-positivos, dependendo da presença ou não do gene SRY que normalmente se encontra em Y cromossomo participando da determinação testicular. Neste artigo, são descritos os antecedentes pessoais e os achados clínicos de uma criança com anomalias de meato urinário em que foi identificado um complemento cromossômico 46,XX. Além disso, foi rea -lizada hibridação in situ fluorescente em linfócitos de sangue periférico que demonstrou a ausência do gene SRY e confirmou a presença de dois cromossomos X.
Subject(s)
Humans , Male , Child, Preschool , 46, XX Disorders of Sex Development , In Situ Hybridization, Fluorescence , Genes, sry , Ovotesticular Disorders of Sex DevelopmentABSTRACT
PURPOSE: Patients with ovotesticular disorder of sex development (DSD) and mixed gonadal dysgenesis (MGD) usually present with asymmetric gonads and have wide phenotypic variations in internal and external genitalia. The differential diagnosis of these conditions is based on karyotype and pathological findings of the gonads. This study investigated the clinical features at presentation, karyotype, sex of rearing, and pubertal outcomes of patients with ovotesticular DSD and MGD.METHODS: The study comprised 23 patients with DSD who presented with asymmetric gonads. The presenting features, karyotype, sex of rearing, and pubertal outcomes were reviewed retrospectively.RESULTS: All 23 patients presented with ambiguous genitalia at a median age of 1 month (range, 1 day–1.6 years). Müllerian duct remnants were identified in 15 of 23 patients (65.2%). Fourteen patients were diagnosed with ovotesticular DSD, whereas the other 9 were diagnosed with MGD. Eight of 14 patients (57.1%) with ovotesticular DSD were raised as males, while 7 of 9 patients with MGD (77.8%) were assigned as males. One male-assigned patient with ovotesticular DSD changed to female sex at age 20 years.CONCLUSION: Patients with ovotesticular DSD and MGD manifest overlapping clinical presentations and hormonal profiles. It is difficult to determine the sex of rearing and predict long-term pubertal outcomes. Therefore, long-term follow-up is required to monitor spontaneous puberty, sex outcome, and urological and gynecological complications.
Subject(s)
Adolescent , Female , Humans , Male , Diagnosis, Differential , Disorders of Sex Development , Follow-Up Studies , Genitalia , Gonadal Dysgenesis , Gonadal Dysgenesis, Mixed , Gonads , Karyotype , Ovotesticular Disorders of Sex Development , Puberty , Retrospective StudiesABSTRACT
Androgen insensitivity syndrome (AIS), an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor (AR) gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS. Genetic analysis of AR gene revealed the existence of 10 different mutations, of which five were novel (c.2112 C>G[p.S704R], c.2290T>A[p.Y764N], c.2626C>T[p.Q876X], c.933dupC[p.K313Qfs∗28], and c.1067delC[p.A356Efs∗123]); the other five were previously reported (c.1789G>A[p.A597T], c.2566C>T[p.R856C], c.2668G>A[p.V890M], c.2679C>T[p.P893L], and c.1605C>G[p.Y535X]). Regarding the distribution of these mutations, 60.0% were clustered in the ligand-binding domain of AR gene. Exons 1 and 8 of AR gene each accounted for 30.0% (3/10) of all mutations. Most of the truncation mutations were in exon 1 and missense mutations were mainly located in exons 4-8. Our study expands the spectrum of AR gene mutations and confirms the usefulness of AR gene sequencing to support a diagnosis of AIS and to enable prenatal or antenatal screening.
ABSTRACT
Objective To detect SRY mutation in 46,XY disorder of sex development (46,XY DSD), analyze SRY mutation frequency , and to define the clinical features of the patients with the mutation .Methods A total of sixty-three 46,XY DSD patients admitted to department of endocrinology of Peking Union Medical College Hospital from 2009 to 2014 were enrolled and detailed clinical data were collected .Genomic DNA was extracted from peripheral blood, and SRY was amplified and sequenced .The mutation was identified by comparing with the online database , and the clinical features were analyzed .Results Three novel mutations of SRY gene were detected in 3 of 63 pa-tients (5%).The 3 patients' social genders were all female and their karyotypes are 46, XY.Vaginal and uterine structures were present .Sex hormone profiles were consistent with hypergonadotropic hypogonadism .The 3 novel mutations were Pro131His, R76C and L35Afs*25.The former two were mutations in the nuclear localization signal regions of HMG box and highly-conservative amino acids were affected .The latter one was a frameshift mutation re-sulting in deletion of the entire HMG box .All these were presumably affecting the functional domain of SRY protein severely.Conclusions This study identified three novel mutations of SRY gene causing 46,XY DSD.The detection rate of SRY mutation was about 5%.It is recommended that SRY testing be performed to identify the etiology of the disease .
ABSTRACT
Objetivo: Se presenta el caso clínico de una paciente femenina de 27 años con enfermedad renal crónica estadio V a los 19 años, en condición pos trasplante renal quien es referida a la consulta de Endocrinología por amenorrea primaria. Presentación del caso: Al examen físico se evidencia: fenotipo femenino armónico, talla normal, vello púbico Tanner IV y axilar presente, mamas Tanner I, cardiopulmonar: sin alteraciones. Abdomen: lesión ocupante de espacio en fosa ilíaca derecha, no doloroso, compatible con riñón intrapélvico y lesión ocupante de espacio en canal inguinal derecho <1cm, no doloroso, móvil, sin hernias inguinales ni lesión ocupante de espacio en hipogastrio. Genitales externos: labios mayores de aspecto y configuración normal, Prader 1, no se palpan tumoraciones. Ecosonograma inguinal y pélvico: Riñón intrapélvico, no se observó útero ni gónadas. Cariotipo 46,XY. Estudio genético: Amplificación por PCR del ADN del gen WT1: sustitución de aminoácido C> T IVS9 + 4. Se realiza gonadectomía bilateral, cuya biopsia reportó: ovotestis bilateral sin gonadoblastoma. Conclusiones: La presencia de trastornos de la diferenciación sexual tipo ovotesticular sin gonadoblastoma, es el primer caso reportado en la literatura venezolana.
Objective: Case report of female patient 27 years old, with stage V chronic kidney disease, and received a living donor kidney transplant at 19 age, who is referred to Endocrine Unit for primary amenorrhea. Case report: Physical examination evidenced: Harmonic female phenotype, normal height, Tanner IV pubic hair and axillary hair present, breast Tanner I, cardiopulmonary: unchanged. Abdomen: Space-occupying lesion in the right iliac fossa, painless, compatible with intrapelvic kidney and space-occupying lesion in the right inguinal canal <1 cm, painless, mobile, without inguinal hernia or space-occupying lesion in lower abdomen. External genitalia: Majora labia with appearance and normal configuration, Prader 1, no palpable tumors. Inguinal and pelvic sonography: intrapelvic kidney, uterus and gonads were not observed. 46, XY karyotype. Genetic study: PCR Amplification DNA of WT1 gene: Amino acid substitution C> T + 4. IVS9. Bilateral gonadectomy was performed, the biopsy reported: Bilateral ovotestis without gonadoblastoma. Conclusion: The presence of disorder of sexual development and ovotestis without gonadoblastoma and germ cell tumor are unusual presentations of this syndrome, is the first case reported in literature.
ABSTRACT
PURPOSE: To identify the clinical characteristics of SRY-negative male patients and genes related to male sex reversal, we performed a retrospective study using cases of 46,XX testicular disorders of sex development with a review of the literature. MATERIALS AND METHODS: SRY-negative cases of 46,XX testicular disorders of sex development referred for cytogenetic analysis from 1983 to 2013 were examined using clinical findings, seminal analyses, basal hormone profiles, conventional cytogenetic analysis and polymerase chain reaction. RESULTS: Chromosome analysis of cultured peripheral blood cells of 8,386 individuals found 19 cases (0.23%) with 46,XX testicular disorders of sex development. The SRY gene was confirmed to be absent in three of these 19 cases (15.8%). CONCLUSION: We report three rare cases of SRY-negative 46,XX testicular disorders of sex development. Genes on autosomes and the X chromosome that may have a role in sex determination were deduced through a literature review. These genes, through differences in gene dosage variation, may have a role in sex reversal in the absence of SRY.
Subject(s)
Humans , Male , Azoospermia , Blood Cells , Cytogenetic Analysis , Disorders of Sex Development , Gene Dosage , Genes, sry , Infertility , Polymerase Chain Reaction , Retrospective Studies , Sexual Development , X ChromosomeABSTRACT
As anomalias da diferenciação sexual têm-se constituído em um formidável desafio quanto ao diagnóstico e à conduta, colocando o paciente, os familiares e os profissionais da equipe de saúde na difícil situação de definir a melhor opção quanto ao gênero de criação. Uma terminologia confusa e estigmatizante tem sido adotada e, nesse sentido, o Consenso de Chicago propõe várias modificações no sentido de minimizar os desconfortos graças a uma terminologia que nem sempre auxilia na solução de problemas. Os autores fazem uma análise crítica da classificação sugerida pelo Consenso, levantando a questão de que, na nova classificação, também não se resolvem certos problemas terminológicos e continua a se criar algum grau de estigmatização. Em primeiro lugar, a sugestão de se incluir o cariótipo no nome da doença supõe, erroneamente, que os pacientes não tenham conhecimento do que significa ser 46,XY ou 46,XX. Uma criança criada no sexo feminino com uma anomalia da diferenciação sexual (ADS) 46,XY não vai entender porque está no sexo feminino se seu cariótipo é "masculino". A substituição do termo hermafroditismo verdadeiro por ADS ovotesticular está longe de resolver o problema de estigmatização causado por "hermafroditismo". O termo ovotesticular é claramente entendido como uma fusão entre ovário e testículo e não será aceito com "naturalidade". Se, por um lado, é muito satisfatório que a questão da nomenclatura seja discutida, por outro lado devemos escolher termos alternativos que sejam realmente neutros e não tragam, em si, a conotação de um sexo que pode não condizer com o escolhido para aquele paciente em particular. Um ponto em que todos concordamos é que a substituição de intersexo por anomalia da diferenciação sexual (ADS) ou, disorder of sex development (DSD), na língua inglesa, cai muito melhor e não dá a conotação de um "sexo intermediário" como o nome antigo proporcionava.
Disorders of sex development have posed a tremendous challenge not only in the diagnosis but also in the treatment, placing the patient, the family members, and the health team in the difficult task of attributing the best sex of rearing for that specific patient. A confusing and stigmatizing nomenclature has been employed and the Chicago Consensus tried to minimize the discomfort with modifications of the current terminology. The authors perform a critical analysis of the Consensus, raising the question that the new terminology does not solve the problems and persist being stigmatizing to the patient and to the family. First of all, the inclusion of the karyotype in the name of the disease holds the false premise that the patients do not know the meaning of a 46,XY or a 46,XX karyotype. A child raised in the female sex will not understand that her disease holds a "male" karyotype in its name (46,XY DSD). The substitution of ovotesticular DSD for true hermaphroditism maintains the stigma of the name since ovotesticular is easily perceived as ovarian and testicular tissues. If, on one hand, the recognition of using terms like intersex and hermaphroditism are stigmatizing, on the other hand, we need terms that are really neutral to not create problems of sexual identification. One point in which there is consensus is that the change of the term "intersex" for "disorder of sex development" is highly desirable and eliminates the idea of an "intermediate sex".