Síndrome de insensibilidad completa a andrógenos / Complete androgen insensitivity syndrome

El síndrome de insensibilidad a los andrógenos (SIA), conocido también como un síndrome de feminización testicular, incluye un grupo variado de mutaciones que se relacionan con la disfunción de los receptores de andrógenos y la resistencia de los tejidos diana a la acción de las hormonas masculinas. Es causado por alteraciones genéticas localizadas en la secuencia de codificación de los receptores de andrógenos ligada al cromosoma Xq11 - 12, el gen que codifica al receptor de los andrógenos, de un individuo genéticamente masculino (46 XY). Las formas clínicas moderada, parcial o completa, dependen del grado de insensibilidad androgénica. Los avances en las causas genéticas han permitido que estas condiciones congénitas de desarrollo del sexo cromosómico, gonadal o anatómico atípico sean denominados trastornos de diferenciación sexual

Androgen insensitivity syndrome (AIS), also known as testicular feminization syndrome, includes a diverse group of mutations that are related to androgen receptor dysfunction and resistance of target tissues to the action of hormones masculine. It is caused by localized genetic alterations in the androgen receptor coding sequence linked to chromosome Xq11-12, the gene encoding the androgen receptor, of a genetically male (46 XY) individual. Moderate, partial, or complete clinical forms depend on the degree of androgen insensitivity. Advances in genetic causes have allowed these congenital conditions of atypical chromosomal, gonadal, or anatomical sex development to be called disorders of sexual differentiation

Androgen Insensitivity Syndrome with Bilateral Cryptorchidism and Seminoma in Tibet:Report of One Case / 中国医学科学院学报

Androgen insensitivity syndrome(AIS)with bilateral testicular malignant transformation is very rare,and its diagnosis should be based on clinical manifestations,physical examination,serological findings,karyotype analysis,and pathological findings.This study reported a case of complete androgen insensitivity syndrome among Tibetan in Tibet.It took 17 years from the discovery of congenital absence of uterus to bilateral pelvic mass resection.Pathological examination confirmed that bilateral pelvic space occupying lesions were dysplastic testicular tissue with seminoma and sertoli cell adenoma-like nodules.This study summarized the clinicopathological features to deepen the understanding of the disease.

Atendendo mulheres com cariótipo 46, XY / Attending women with 46, XY karyotype

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)

Complete Androgen Insensitivity Syndrome: A Rare Case of Prenatal Diagnosis / Síndrome de insensibilidade completa aos androgênios: um caso raro de diagnóstico pré-natal

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.

Complete Androgen Insensitivity in two Filipino siblings: A case report

@#Androgen insensitivity syndrome is an X-linked recessive condition resulting in a failure of normal masculinization of the external genitalia in a chromosomally male individual. We describe two phenotypically female siblings aged 27 and 18 years, who presented with primary amenorrhea. The older sibling first consulted because of her desire to be pregnant while her younger sibling consulted upon the physician’s advice. Clinical presentation, physical examination, hormonal and imaging studies and a male (46XY) karyotype confirmed the diagnosis of Complete Androgen Insensitivity Syndrome (AIS) in both individuals. Both of them underwent exploratory laparotomy with histopathology confirming presence of immature testicular tissue. Hormone replacement therapy was then started. Both were advised to undergo psychosocial counseling and both chose to be women. This case report is significant since there are only a few local case reports about siblings presenting with this condition.

Síndrome de insensibilidad a andrógenos: revisión bibliográfica a propósito de 5 casos / Androgen insensitivity syndrome: literature review about 5 cases

El síndrome de insensibilidad a andrógenos (AIS en la sigla inglesa) es una entidad muy poco frecuente en endocrinología. Se caracteriza por la mutación del receptor de andrógenos de magnitud variable, por medio del cual individuos 46,XY no se virilizan normalmente, a pesar de conservar sus testículos y tener concentraciones de testosterona en rango masculino. El cuadro clínico es variable y depende la profundidad de la alteración del receptor. En un extremo, hay casos de insensibilidad androgénica completa (CAIS) con fenotipo femenino. En el otro extremo hay insensibilidad parcial (PAIS) que se extiende desde el fenotipo femenino, con o sin ambigüedad genital, hasta los casos de hombres infértiles o con subvirilización, que presentan insensibilidad androgénica más leve. En los fenotipos femeninos, los testículos suelen estar en posición ectópica y aquellos ubicados dentro del abdomen tienen riesgo de malignizarse, por lo que suelen extirparse. Estos son los casos de más difícil manejo, pues aparte de la necesidad de gonadectomía seguida de terapia hormonal femenina, existe una vagina estrecha y en fondo de saco ciego y que suele requerir corrección quirúrgica para permitir la actividad sexual. En este trabajo presentamos 5 casos de AIS vistos recientemente en 2 centros clínicos de Santiago y que ilustran la heterogeneidad de presentación. Además, hacemos una revisión actualizada de los criterios diagnósticos, los tratamientos más adecuados y el manejo global de esta condición.

The Androgen insensitivity syndrome (AIS, in its English acronym) is a very rare entity in endocrinology. It is characterized by a variable magnitude androgen receptor mutation, whereby 46, XY individuals are not normally virilized, despite retaining their testicles and having testosterone concentrations in the male range. The clinical picture is variable and depends on the depth of the receptor alteration. At one extreme, there are cases of complete androgenic insensitivity (CAIS) with a female phenotype. At the other extreme, there is partial insensitivity (PAIS) that extends from the female phenotype, with or without genital ambiguity, to cases of infertile or undervirilized men, who have milder androgenic insensitivity. In female phenotypes, the testes are usually in an ectopic position and those located within the abdomen are at risk of malignancy, and therefore are usually removed. These are the most difficult cases to manage because apart from the need for gonadectomy followed by female hormonal therapy, there is a narrow vagina and a deep blind pouch that usually requires surgical correction to allow sexual activity. In this work, we present 5 cases of AIS recently seen in 2 clinical centers in Santiago and that illustrate the heterogeneity of presentation. In addition, we make an updated review of the diagnostic criteria, the most appropriate treatments, and the overall management of this condition.

Detección del síndrome de Morris con técnica imagenológica híbrida: reporte de casos / Detection of the Morris syndrome with a hybrid imaging technique: case report

El síndrome de Morris es un trastorno genético recesivo ligado al cromosoma X. Se caracteriza por fenotipo femenino y cariotipo 46 XY. Las gónadas pueden estar localizadas en los labios mayores, el canal inguinal o intraabdominal. En los casos en los que la localización está en el conducto inguinal o labios mayores, las gónadas son confundidas con hernias y son extirpadas en la infancia; cuando son intraabdominales aproximadamente el 30 % tienen el riesgo de desarrollar tumores gonadales en la edad adulta, por lo que es necesario su extirpación quirúrgica. La localización de estas se realizan con ecografía, tomografía o resonancia magnética, pero en ocasiones no es posible identificar estas estructuras, es allí donde nosotros proponemos la tomografía por emisión de positrones con 18-Fluordesoxiglucosa como herramienta diagnostica para localizar el tejido gonadal, aprovechando la captación fisiológica de este radiotrazador en el tejido testicular.

Morris Syndrome is a recessive genetic disorder linked to the X chromosome. It is characterized by a feminine phenotype and 46 XY karyotype. Gonads can be localized at the upper lips and the inguinal or intra-abdominal canal. In cases where the localization can be at the inguinal conduct or upper lips, gonads are mistaken for hernias and they are removed in childhood; when they are intra-abdominal, approximately 30% has risks of developing gonadal tumors at adulthood, so is necessary its surgical removal. Their localization can be made by ultrasound scans, tomography or magnetic resonance, but sometimes is not possible to identify these structures, so this is where we propose 18-Fluorodeoxyglucose positron emission tomography as a diagnostic tool to localize the gonadal tissue, exploiting the physiological capture of this radiotracer at the testicular tissue.

Síndrome de insensibilidad androgénica. A propósito de un caso clínico / Androgenic insensitivity syndrome. About a clinical case

RESUMEN El síndrome de insensibilidad androgénica (SIA) es una de las anormalidades de la diferenciación sexual (desarrollo sexual diferente). Es un trastorno genético dependiente del cromosoma X, produce una alteración en el receptor de andrógenos, se asocia con testículos en las mujeres cuyo cariotipo es XY y con agenesia vaginal y uterina. Acuden a la consulta médica los padres con su hija recién nacida de 12 días de edad. Motivo de consulta: masa en la región inguinal derecha. Examen físico: signos vitales normales, activa al manejo, reactiva. Se observa una masa en la región inguinal derecha de aproximadamente 2 cm de diámetro, reductible, no dolorosa. Genitales externos femeninos: normales. La paciente es referida al Servicio de Cirugía para proceder a la corrección del defecto herniario. Se indica realizar un estudio citogenético y medir los niveles hormonales en sangre. Resultado del estudio anatomopatológico posquirúrgico, luego de 7 días de haber sido intervenida quirúrgicamente: "Tejido gonadal de tipo testicular con zonas de congestión vascular y hemorragia focal". Los niveles hormonales sanguíneos son normales; el cariotipo es normal masculino XY. Diagnóstico: debido a que el resultado del cariotipo es concluyente, se diagnostica síndrome de insensibilidad androgénica (SIA)" completo.Palabras claves: síndrome de insensibilidad androgénica, hernia inguinal, cariotipo

ABSTRACT Androgen insensitivity síndrome (AIS) is one of the causes of abnormalities in sexual differentiation (different sexual development). SIA is an X-linked genetic condition caused by an androgen receptor disorder, associated with vaginal and uterine agenesis, and the presence of testicles in women with an XY karyotype. Parents with 12-day-old neonates go to medical consultation. The reason for consultation is a mass in the right inguinal region. On physical examination: normal vital signs, active on management, reactive. A mass is observed at the level of the right inguinal region of approximately 2 cm in diameter, reducible and not painful. Female external genital with normal characteristics. The patient is referred for surgery to correct hernia defect. A cytogenetic study and blood hormone leves are indicated. Seven days after the intervention, parents came with the results of the postoperative pathological study: testicular gonadal tissue with áreas of vascular congestion and focal hemorrhage. Blood hormonal lever are normal and anormal XY male karyotype is seen. Diagnosis: the result of the karyotype is conclusive and a complete AIS is diagnosed.Keywords:androgen insensitivity syndrome, inguinal hernia, karyotype.

Síndrome de Insensibilidad Completa a Andrógenos (SICA): reporte de un caso clínico / Complete Androgen Insensitivity Syndrome (CAIS): report of a clinical case

INTRODUCTION: Complete Androgen Insensitivity Syndrome (CAIS) is a X-linked recessive disorder characterized by a complete resistance of the Androgen Receptor (AR) to androgens. As a result, affected individuals present complete female external genitalia, but are genetically male with a 46, XY karyotype. The typical presentation for this syndrome is either inguinal swellings in a new born or infant, or primary amenorrhoea in an adolescent. CAIS is commonly diagnosed in one of these clinical scenarios, although recently prenatal diagnosis has been reported. We present a case of a phenotypically female infant with an inguinal swelling, which was biopsied and exposed as testicular tissue, doing the diagnosis of CAIS. A review of the literature on this disorder is made.

Safety and efficacy of Vecchietti vaginoplasty in vaginal agenesis: cohort study. Medellín, Colombia 2007-2012 / Segurança e eficácia da vaginoplastia de Vecchietti na agenesia vaginal: coorte de 2007 a 2012 / Seguridad y eficacia de la vaginoplastia de vecchietti en agenesia vaginal: estudio de cohorte, en medellín, colombia, 2007 a 2012

RESUMEN Objetivo: describir la técnica de vaginoplastia de Vecchietti (TVV) en pacientes diagnosticadas con agenesia vaginal secundaria y hacer una aproxima- ción a la seguridad y eficacia de esta técnica. Materiales y métodos: cohorte histórica de pacientes con agenesia vaginal secundaria al síndrome de Mayer-Rokitansky-Kuster-Hauser y al síndrome de insensibilidad androgénica, a quienes se les realizó vaginoplastia por técnica de Vecchietti en el Hospital Universitario San Vicente Fundación, institución de referencia, de alta complejidad, en el periodo 2007 a 2012. Se excluyeron quienes tenían una vagina funcional para relaciones coitales. Muestreo consecutivo. Se midieron variables socio- demográficas, clínicas, de seguridad y de eficacia. Se utilizó estadística descriptiva. Resultados: el principal motivo de consulta fue la amenorrea primaria (69,2 %). Las malformaciones asociadas fueron agenesia renal derecha (15,4 %) y malformaciones esqueléticas (15,4 %). Se presentó una perforación intraoperatoria de la vejiga y tres complicaciones menores (23,1 %) en el posoperatorio. En el 84,6 % de ellas se obtuvo una vagina funcional a un año de seguimiento. Conclusiones: la TVV es una técnica quirúrgica simple que ha permitido obtener resultados funcionales satisfactorios con complicaciones menores. Se requieren estudios con grupo control para tener una mejor evaluación de la eficacia de las diferentes técnicas de construcción de la neovagina.

ABSTRACT Objective: To describe the Vecchietti vaginoplasty technique (VVT) in patients diagnosed with sec- ondary vaginal agenesis and to analyze the safety and efficacy of this technique. Materials and methods: Historical cohort of patients with vaginal agenesis secondary to Mayer- Rokitansky-Kuster-Hauser and androgen insensitivity syndromes, subjected to vaginoplasty using the Vecchietti technique at San Vicente Fundación University Hospital, a high complexity referral institution located in the city of Medellín, during the time period between 2007 and 2012. Patients with functional a vagina for intercourse were excluded. Sampling was consecutive. Sociodemographic, clinical, safety and efficacy variables were measured. Descriptive statistics were used. Results: The main complaint was primary amenorrhea (69.2%). Associated malformations included right renal agenesis (15.4%) and skeletal malformations (15.4%). There was one intra-operative bladder perforation and, postoperatively, there were three (23.1%) minor complications. At 1-year follow-up, a functional vagina had been obtained in 84.6% of cases. Conclusion: Vecchietti vaginoplasty is a simple surgical technique resulting in satisfactory functional outcomes with only minor complications. Further studies with control groups are required in order to better assess the efficacy of the various techniques used for neovagina creation.

RESUMO Objetivo: descrever a técnica da vaginoplastia de Vecchietti (TVV) em pacientes diagnosticadas com agenesia vaginal secundária e fazer uma abordagem a respeito da segurança e eficácia desta técnica. Materiais e métodos: coorte histórica de pacientes com agenesia vaginal secundária à síndrome de Mayer-Rokitansky-Kuster-Hauser e à síndrome de insensibilidade androgênica, que foram submetidas a uma vaginoplastia pela técnica de Vecchietti no Hospital Universitário San Vicente Fundación, estabelecimento de referência, de alta complexidade, no período 2007-2012. Foram excluídas aquelas pacientes que tinham uma vagina funcional para relações coitais. Amostragem consecutiva. Foram mensuradas diversas variáveis sociodemográficas, clínicas, de segurança e de eficácia, utilizando o método de estatística descritiva. Resultados: o principal motivo de consulta foi a amenorreia primária (69,2%). As malformações correlatas foram agenesia renal direita (15,4%) e malformações esqueléticas (15,4%). Verificouse uma perfuração intraoperatória da bexiga e três complicações menores (23,1%) no pós-operatório. Em 84,6% delas conseguiu se uma vagina funcional durante o primeiro ano de acompanhamento. Conclusão: a TVV é uma técnica cirúrgica simples que permitiu obter resultados funcionais satisfatórios com complicações menores. É preciso levantar estudos com grupo-controle para fazer uma melhor avaliação da eficácia das diferentes técnicas de construção da neovagina.

Analysis of AR gene variant in an infant with complete androgen insensitivity syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variant of AR gene in an infant with complete androgen insensitivity syndrome.@*METHODS@#The coding regions and splicing sites of the AR gene were subjected to PCR amplification and direct DNA sequencing. Fluorescence quantitative PCR was also used to detect copy number alterations of exons 2 to 8 of the AR gene.@*RESULTS@#Deletion of exons 2 to 8 was detected in the proband, and the results were verified among the family members.@*CONCLUSION@#Hemizygotic deletion of exons 2 to 8 of the AR gene probably underlies the complete androgen insensitivity syndrome in this infant.

External quality assessment on CD4+ T-Cell Count using in-house proficiency testing panels for CD4 Count laboratories in Addis Ababa, Ethiopia

BACKGROUND: CD4+ T-cell count External Quality Assessment program is important for the evaluation of performance of CD4 count laboratories. The aim of this study was to assess the quality of CD4count laboratory performance using in-house Proficiency testing panels that perform routineCD4 counts in Addis Ababa, Ethiopia, 2013/14. METHODS: Participating laboratories were 20, 23 and 25 in trials 1, 2 and 3, respectively. In-house prepared fresh whole blood samples both with "normal" and "low" CD4 values were sent to participating laboratories. Percentage and absolute counts of CD4+ T-lymphocytes were done using their routine procedures. Data were analyzed for each trial including trimmed mean, standard deviation (SD), percent coefficient of variation (%CV), residual, and standard deviation index (SDI) values for both absolute counts and percentages of CD4+ lymphocytes (%CD4). RESULTS: Most participating laboratories produced results that were within 2SD of the mean. Average inter-laboratory precision (trimmed %CV) was 10.87% and 5.14% for CD4 absolute counts and %CD4, respectively. For normal material, the trimmed mean %CV was 9.59% and3.23% for CD4 absolute counts and %CD4, respectively. For low material, the trimmed mean % CV was 12.15% and 7.05% for CD4 absolute counts and %CD4 respectively. BDFACSCount™ users showed the best accuracy and precision as evidenced by longitudinal analysis. CONCLUSION: This study was found to help facilities in early identifying their gaps with regard to their CD4 count performance and in avoiding the challenges encountered during participation in external EQA providers like the high cost, transportation problem, feedback delay and CD4laboratory coverage

Androgen insensitivity syndrome: a review

ABSTRACT Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.

A Case of Androgen Insensitivity Syndrome with Intraabdominal Testes in a 62 year old woman

@#Androgen Insensitivity Syndrome (AIS) is a disorder wherein a patient presents with a female phenotype but is actually genetically male with an XY karyotype. Typically, AIS is diagnosed at the beginning of second decade, when a phenotypically female patient complains of amenorrhea. It is extremely rare to make a first diagnosis of AIS after the fifth decade of life. This case report presents a 62-year old female who consulted because of primary amenorrhea and intraabdominal mass. Patient was diagnosed with Complete Androgen Insensitivity Syndrome based on physical exam findings, imaging studies, endocrine tests and karyotyping. She underwent exploratory laparotomy, adhesiolysis and bilateral orchiectomy. This report will discuss diagnosis and appropriate management of patients with Complete Androgen Insensitivity.

Phenotypic and molecular characteristics of androgen insensitivity syndrome patients / 亚洲男科学杂志(英文版)

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.

Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent Müllerian duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

Female with 46, XY karyotype

Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomal, gonadal, and phenotypic sex. 46, XY DSD can result from disorders of testicular development or disorders of androgen synthesis/action. Prophylactic gonadectomy should be considered in patients with 46, XY DSD because of the increased risk of gonadal malignancy. We report two rare cases of 46, XY DSD, including XY pure gonadal dysgenesis and complete androgen insensitivity syndrome, who underwent a prophylactic gonadectomy.

Analysis of AR gene mutation in a family affected with complete androgen insensitivity syndrome using long chain RT-PCR / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of androgen receptor (AR) gene in a patient with complete androgen insensitivity syndrome (CAIS) and his family members.</p><p><b>METHODS</b>Total RNA and genomic DNA were extracted from the peripheral blood samples derived from the proband and her family members. Sequences of 7 exons of the AR gene were amplified with reverse transcriptase PCR(RT-PCR) and subjected to direct sequencing. Suspected mutation was also analyzed with PCR-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing.</p><p><b>RESULTS</b>DNA sequencing has revealed a nucleotide change (2880A>G) in the pedigree, which resulted in a missense mutation (R840H).</p><p><b>CONCLUSION</b>A prenatal diagnostic method was established for detecting mutation of the AR gene in the pedigree. Long chain RT-PCR was first used for the detection of AR gene mutations.</p>

17α-hydroxylase Deficiency Mimicking Hyperaldosteronism by Aldosterone-producing Adrenal Adenoma / 대한내과학회지

17α-hydroxylase deficiency is a rare cause of congenital adrenal hyperplasia and is characterized by primary amenorrhea, delayed puberty and hypertension. Although 17α-hydroxylase deficiency mimics mineralocorticoid-induced hypertension, impaired sexual development can aid in the differential diagnosis of this disease. A 32-year-old woman, who had a history of testicular feminization syndrome, presented with hypertension. Her aldosterone level was elevated whereas plasma renin activity was reduced, and her computed tomography scan showed a left adrenal adenoma, which was thought to be an aldosterone producing adenoma. A left adrenalectomy was performed to treat hypertension; however, the condition did not improve. The hormonal tests revealed high levels of plasma progesterone, mineralocorticoid and adrenocorticotropic hormone, and low levels of 17a hydroxyprogesterone, cortisol and sex hormones. The patient was diagnosed with 17α-hydroxylase deficiency and commenced on prednisolone, which controlled hypertension. Here, we report a case of 17α-hydroxylase deficiency mimicking hyperaldosteronism via aldosterone-producing adrenal adenoma.

Androgen insensitivity syndrome (AIS) / Philippine Journal of Obstetrics and Gynecology

Androgen Insensitivity Syndrome (AIS) is a rare condition, it is an X-linked-mutation that is considered as a disease caused by resistance of androgen receptor to its actions. It is expressed in a variety of phenotypes ranging from male infertility to completely normal female external genitalia. This is a case of a 25 year-old with Complete Androgen Insensitivity Syndrome (CAIS), presented as phenotypical female with secondary sexual development, bilateral inguinal masses. Gonadectomy, estrogen replacement therapy and psychological support are part of long term management.