Pure 46, XY gonadal dysgenesis and 46, XY complete androgen insensitivity syndrome: A case report.

BACKGROUND: 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 androgen synthesis. METHODS: We present 2 rare cases of 46, XY DSD, specifically XY pure gonadal dysgenesis and complete androgen insensitivity syndrome. RESULTS: Both cases underwent prophylactic gonadectomy due to the elevated risk of gonadal malignancy. Bilateral gonadoblastoma and dysgerminoma were diagnosed on one side, while Leydig cell hyperplasia and only Sertoli cells were diagnosed in the seminiferous tubules on both sides. The normal menstruation for the pure gonadal dysgenesis patient only as CAIS patients never menstruate. Estrogen replacement therapy was administered periodically to promote the development of secondary sexual characteristics and menstruation in pure gonadal dysgenesis case, as well as to prevent osteoporosis. Follow-up examinations revealed no tumor recurrence, and the patient with Swyer syndrome had regular menstrual cycles. CONCLUSION: Laparoscopic bilateral prophylactic gonadectomy and long-term hormone therapy with patient counseling and support are recommended.

MYRF mutation leads to a single manifestation of sexual development and mimics partial androgen insensitivity syndrome: a case report and literature review.

OBJECTIVE: To highlight the challenges in diagnosing 46, XY disorder of sex development related to MYRF mutation. METHODS: We present an unusual case of a 12-year-old female child came for enlargement of clitoris and initially diagnosed as partial androgen insensitivity syndrome (AIS). RESULTS: On examination, the patient's vulva was found virilized with 3cm-long clitoris. Her peripheral blood karyotype was 46, XY. The ultrasound showed an empty pelvis and hormone results confirmed hyperandrogenism. Therefore, the partial AIS was suspected, but the following whole exon sequencing indicates a pathological missense mutation in MYRF. Further investigation and surgery did not reveal any brain, heart, lung or diaphragm lesions related to MYRF, but only maldeveloped internal genitalia and a persistent urachus. Her serum testosterone dropped to normal after surgical removal of the remaining ipsilateral testis and epididymitis without spermatogenesis as shown by pathology. CONCLUSION: Due to the karyotype, hyperandrogenism, empty pelvis but a virilism after puberty, the patient was initially diagnosed as partial AIS. This misleading clinical diagnose will not be verified as the MYRF mutation if without the whole exon sequencing, particularly in the absence of obvious brain, heart, lung and diaphragm lesions as in this case.

A case of mild partial androgen insensitivity syndrome in a juvenile boy.

Androgen insensitivity syndrome (AIS) is a rare disorder with X-linked recessive inheritance in 46 XY patients. The clinical manifestations vary between patients, especially regarding external genitalia development. Herein, the case of AIS in a 13-year-old male, who was born with hypospadias and presented to the hospital with gynaecomastia that had developed from 8 years of age, is reported. No micropenis, cryptorchidism or bifid scrotum were found. Testis volume was 12 ml on both sides. His testosterone and luteinizing hormone levels were normal compared with sex- and age-adjusted reference range. His bone age was approximately 13 years according to Greulich-Pyle assessment. Sequence analysis of the androgen receptor (AR) gene revealed a mutation (c.2041A>G) in exon 4, a novel mutation site in the AR gene. Prediction analysis suggested this to be a disease-causing variant. A milder clinical presentation and normal hormone levels in cases of partial AIS might differ from the usually reported signs and symptoms. A diagnosis of AIS should not be ignored in teenage patients who present with gynaecomastia and hypospadias, but normal hormone levels.

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.

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.

Síndrome de insensibilidad parcial a andrógenos con restos müllerianos. Descripción de un caso / Partial androgen insensitivity syndrome with persistent müllerian remnants. A case report

No disponible

Adenoma de células de Sertoli bilateral en paciente con síndrome de insensibilidad a los andrógenos / Bilateral Sertoli cell adenoma in a patient with androgen insensitivity syndrome

El síndrome de insensibilidad a los andrógenos se caracteriza por la presencia de fenotipo femenino, gónadas masculinas y cariotipo 46,XY. Es la causa más común de seudohermafroditismo masculino y la tercera causa más frecuente de amenorrea primaria, después de la disgenesia gonadal y la ausencia congénita de vagina. Es una entidad cuya importancia radica en su diagnóstico precoz en la pubertad por el riesgo de desarrollo de tumoraciones testiculares. En este artículo se presenta un caso de diagnóstico tardío de síndrome de insensibilidad a los andrógenos asociado a adenoma de células de Sertoli (AU)

Androgen insensitivity syndrome is characterized by the presence of a female phenotype, masculine gonads, and 46,XY karyotype. This syndrome is the most common cause of masculine pseudohermaphroditism and is the third most frequent cause of primary amenorrhea after gonadal dysgenesis and congenital absence of the vagina. The importance of this entity lies in its early diagnosis in puberty because of the risk of testicular tumors. In this article, we present a case of late diagnosis of androgen insensitivity syndrome related to Sertoli cell adenoma (AU)

Síndrome de insensibilidad a los andrógenos familiar / Familial androgen insensitivity syndrome

El síndrome de insensibilidad a los andrógenos es el más frecuente de los trastornos del desarrollo sexual con cariotipo XY y fenotipo femenino. Se debe a una mutación en el gen del receptor de andrógenos, situado en el cromosoma X. El diagnóstico suele realizarse en la infancia por hernias inguinales o en la pubertad por amenorrea primaria. Hay riesgo de malignización de las gónadas, por lo que es necesaria su extirpación. Presentamos una paciente de 25 años con amenorrea primaria diagnosticada de síndrome de insensibilidad a los andrógenos que refiere 4 familiares con el mismo diagnóstico(AU)

Androgen insensitivity syndrome is the most frequent of the sexual development disorders with 46,XY karyotype and female phenotype. This syndrome is due to a mutation in the androgen receptor gene, which lies on the X-chromosome. Diagnosis is usually made in childhood due to inguinal hernias or during puberty due to primary amenorrhea. Gonadal extirpation is required because of the risk of malignant transformation. We present a 25-year-old patient with primary amenorrhea diagnosed with androgen insensitivity syndrome, who reported four relatives with the same diagnosis(AU)

Síndrome de insensibilidad a los andrógenos como causa de amenorrea primaria / Androgen insensitivity syndrome as a cause of primary amenorrhea

El síndrome de insensibilidad a los andrógenos se caracteriza por la presencia de cariotipo 46,XY, fenotipo femenino y presencia de gónadas masculinas. Es la tercera causa más frecuente de amenorrea primaria, tras la disgenesia gonadal y la ausencia congénita de vagina (síndrome de Mayer-Rokitansky-Küster-Hauser). Se trata de una entidad de interés por su relevancia en la identificación sexual y por su posible asociación con tumores malignos de las gónadas masculinas, que hace necesario un correcto diagnóstico y tratamiento quirúrgico. En este artículo se describen dos casos de síndrome de insensibilidad a los andrógenos, con su estudio clínico-genético y tratamiento, así como su seguimiento (AU)

Androgen insensitivity syndrome is characterized by the presence of external female phenotype, 46,XY karyotype and intraabdominal testes. This syndrome is the third most frequent cause of primary amenorrhea, after gonadal dysgenesis and congenital absence of the vagina (Mayer-Rokitansky-Küster-Hauser syndrome). Androgen insensitivity syndrome is of interest due to its role in sexual identification and its possible association with malignant tumors of the male gonads, which require an accurate diagnosis and surgical treatment. We present two cases of androgen insensitivity syndrome. The results of the clinical and genetic examinations, as well as the treatment and follow-up of these two patients, are discussed (AU)

Testicular cancer in androgen insensitivity syndrome in a Mexican population

Male pseudohermaphroditism and androgen insensitivity syndrome cases have an increased risk of developing testicular cancer due to many factors such as mutations, hormonal disturbances involving gonadotropins and cryptorchidism. We describe the clinical features, diagnosis and treatment of two cases with partial androgen insensitivity syndrome and testicular cancer development, which were handled at the National Cancer Institute of Mexico (AU)

No disponible

Síndrome de insensibilidad completa a los andrógenos; diagnóstico y características clínicas / Complete androgen insensitivity syndrome: diagnosis and clinical characteristics

El síndrome de insensibilidad completa a los andrógenos (SICA)es una enfermedad genética producida por mutaciones en elreceptor de andrógenos en individuos con cariotipo masculino(46, XY). Fenotípicamente, estos pacientes tienen genitalesexternos femeninos no ambiguos, bolsa vaginal ciega, estructurasmullerianas ausentes o vestigiales y testículos localizadosen labios, canal inguinal o abdomen. El objetivo de este trabajofue caracterizar a las pacientes con SICA en nuestro centro eidentificar las dificultades diagnósticas de este cuadro. Laproporción de pacientes con antecedente de hernia inguinal enla infancia (83 por ciento) fue significativa. A pesar de esto, la sospechadiagnóstica surgió más tarde, cuando las pacientes se presentaroncon amenorrea primaria. El diagnóstico podría sospecharseprecozmente ya que la hernia inguinal es poco frecuenteen niñas. El diagnóstico precoz es importante para el correctoy oportuno asesoramiento genético.(AU)

Complete androgen insensitivity syndrome (CAIS) is a genetic disease caused by mutations in the androgen receptor gene. CAIS patients are individuals with a 46, XY karyotype. The phenotype consists in female external genitalia, short vagina, absent mullerian structures, and abdominal, inguinal or intralabial testes. Our aim is to describe a group of CAIS patients in our centre and identify the difficulties in the diagnosis. The amount of patients with inguinal hernia in childhood was remarkable (83%). Interestingly, the diagnosis was suspected later when patients presented primary amenorrhea. CAIS must be suspected every time a female child shows inguinal hernia. Early diagnosis is very important for a correct genetic counseling.(AU)

Neovagina con intestino: a propósito de 13 casos / Neovagina with intestine: 13 cases

Introducción. La ausencia o hipoplasia vaginal puede aparecer aislada, asociada a genitales ambiguos, o como variante anatómica en un síndrome de la cloaca. El objetivo fundamental en la creación de una nueva vagina es: conseguir un buen resultado estético, cumplir criterios funcionales (elasticidad, sensibilidad, inclinación fisiológica)y mejorar la calidad de vida de las pacientes evitando el uso de moldes y minimizando la morbilidad de las zonas donantes. En este trabajo presentamos nuestra experiencia en la realización de neovaginas con intestino. Material y métodos. Analizamos el historial clínico de 13 pacientes tratadas quirúrgicamente en los últimos diez años. Diferenciamos dos grupos según la edad, el diagnóstico y el tipo de cirugía: a) un primer grupo de 8 pacientes presentan síndrome de insensibilidad a los andrógenos(4), síndrome de Rokitansky (2), extrofia de cloaca (1) y disgenesiagonadal mixta (1). Este grupo de pacientes fueron intervenidas en la adolescencia con una media de edad de 19 años (11-35 años), realizándoles una neovaginal con sigma; b) un segundo grupo de 5 pacientes con cloaca (3), extrofia de cloaca (1) e hiperplasia suprarrenal congénita(1). Este grupo fue intervenido precozmente con una edad media de un año (4 meses-3 años). El segmento intestinal utilizado como neovagina fue sigma (2), ileon (2) y recto (1), y se realizó durante la cirugía correctora de su malformación congénita. Resultados. Dos pacientes han presentado obstrucción intestinal en el postoperatorio inmediato. Cuatro pacientes han requerido extirpación de un pequeño prolapso vaginal, y tres han necesitado dilataciones vaginales transitorias por estenosis del introito. La evolución a largo plazo ha sido favorable con un excelente aspecto estético. De las 6 pacientes mayores de 15 años, 4 refieren relaciones sexuales plenamente satisfactorias. Conclusiones. Creemos que la neovagina con sigma es en la actualidad la mejor opción en pacientes con ausencia o hipoplasia vaginal. Las ventajas son la posibilidad de cirugía precoz y en un solo tiempo, una neovagina de dimensiones y lubricación adecuadas sin necesidad dedilataciones ni moldes, un aspecto estético excelente, y unas relaciones sexuales satisfactorias (AU)

associated with ambiguous genitalia, or as anatomical variant in a syndrome of sewer. The fundamental aim in the creation of a new vagina is: to obtain a good aesthetic result, to fulfil functional criteria (elasticity, sensibility, physiological inclination) and to improve the quality of life of the patients avoiding the use of molds and minimizing the morbidity of the zones donors. In this work let's sense beforehand our experience in the accomplishment of neovaginas with intestine. Aim and methods. We analyze the clinical record of 13 patients treated surgically in the last ten years. We differentiate two groups according to the age, the diagnosis and the type of surgery: a) the first group of 8 patients present syndrome of insensibility to the androgens (4),syndrome of Rokitansky (2), extrofia of sewer (1) and mixed gonadaldisgenesia (1). This group of patients were controlled in the adolescence by an average of age of 19 years (11-35 years), they fulfilling a neovagina with sigma; b) the second group of 5 patients with sewer (3),extrofia of sewer (1) and congenital suprarrenal hiperplasia (1). This group was controlled prematurely by a middle ages of one year (4months-3 years). The intestinal segment used as neovagina was sigma(2), ileon (2) and rectum (1), and was performed during the surgical correction of her congenital malformation. Results. Two patients have presented intestinal obstruction in the postoperatory immediate one. Four patients have needed removal of a small vaginal prolapse, and three have needed vaginal transitory expansions for introit stenosis. The long-term evolution has been favourable with an excellent aesthetic aspect. Four patients recount sexual fully satisfactory relations. Conclusions. We believe that the neovagina with sigma is at present the best option in patients with absence or hipoplasia vaginal. The advantages are the possibility of precocious and one time correction, a neovagina of dimensions and oiling adapted without need of expansions or molds, an aesthetic excellent aspect, and sexual satisfactory sexual relations (AU)

Síndrome de insensibilidade aos andrógenos: análise clínica, hormonal e molecular de 33 casos / Androgen insensitivity syndrome: clinical, hormonal and molecular analysis of 33 cases

A síndrome de insensibilidade aos andrógenos (AIS) é uma doença com herança ligada ao cromossomo X que afeta pacientes com cariótipo 46,XY, nos quais há prejuízo total (forma completa, CAIS) ou parcial (PAIS) do processo de virilização intra-útero devido à alteração funcional do receptor de andrógenos (AR). Apresentamos uma revisão da AIS e do AR com os dados clínicos, hormonais e moleculares de 33 casos. Analisamos a região codificadora do gene do AR em 33 pacientes de 21 famílias, com quadro clínico e hormonal sugestivo de AIS. Onze pacientes (9 famílias) com diagnóstico de CAIS e 22 pacientes (12 famílias) com diagnóstico de PAIS. Identificamos mutações no gene do receptor androgênico e a etiologia da síndrome de insensibilidade aos andrógenos em 86 por cento das 21 famílias estudadas: 100 por cento das famílias com insensibilidade completa aos andrógenos e 75 por cento das famílias com insensibilidade parcial aos andrógenos. Identificamos 9 mutações no AR descritas anteriormente na literatura (N705S, W741C, M742V, R752X, Y763C, R779W, M807V, R855C e R855H) e 7 mutações foram descritas pela primeira vez nesta casuística (S119X, T602P, L768V, R840S, I898F, P904R e IVS3 - 60 G>A).

Hermafroditismo verdadero asociado a síndrome de insensibilidad a los andrógenos. Revisión de la literatura y diagnóstico diferencial / True hermaphroditism associated to androgenics insensitivity syndrome. Literature revision and diferential diagnosis

El hermafroditismo verdadero es una causa muy poco común de intersexualidad caracterizada por la coexistencia de tejido ovárico y testicular en el mismo individuo, independientemente de su cariotipo, manifestándose en la mayoría de las ocasiones como genitales ambiguos en el recién nacido. Es fundamental establecer un diagnóstico diferencial precoz con otros cuadros clínicos como la disgenesia gonadal mixta o el seudohermafroditismo masculino, para la correcta orientación terapéutica, así como para la asignación del género más apropiado lo antes posible, con objeto de facilitar el adecuado desarrollo físico, psicológico, social y sexual de la persona (AU)