Síndrome da Insensibilidade Androgênica: perfil clínico e epidemiológico de uma série de casos

Introdução: Os Distúrbios do Desenvolvimento Sexual (DDS) resultam de uma interação anormal de fatores genéticos e hormonais implicados no desenvolvimento embrionário da determinação e diferenciação sexual. Os indivíduos com cariótipo 46, XY que apresentaram virilização deficiente da genitália externa são classificados como tendo um quadro sindrômico de Distúrbio do Desenvolvimento Sexual (46, XY DDS), incluindo entre esses a Síndrome da Insensibilidade Androgênica (AIS). Vários genes já foram reconhecidos por sua participação na formação das gônadas e genitálias (interna e externa) entre eles o gene do Receptor de Andrógenos (AR). Objetivo: Analisar os aspectos sócio-epidemiológicos e clínicos de indivíduos com diagnóstico sindrômico de 46, XY Distúrbio do Desenvolvimento Sexual (46,XY DDS) matriculados no Ambulatório de Genética (C-HUPES-UFBA). Metodologia: 13 pacientes com 46, XY DDS e suspeita diagnóstica de AIS, foram selecionados para se traçar o perfil clínico e epidemiológico. Resultados: Entre os pacientes estudados, 07 foram diagnosticados como PAIS e 06 como CAIS, tendo como o sexo de criação, respectivamente, o masculino e o feminino; a média de idade na primeira consulta foi de 06 anos. Cerca de 38% apresentavam história familiar positiva. O motivo de encaminhamento mais frequente foi hipospádia e genitália ambígua. A média do comprimento do falus foi de 2,77 cm. A localização mais comum das gônadas foi na bolsa escrotal. Apenas dois pacientes apresentaram mais de um orifício perineal. Dois pacientes fizeram tratamento medicamentoso e dez foram submetidos à cirurgia corretiva da genitália. Conclusão: Na população estudada o diagnóstico foi mais tardio, isso requer ações sócio-educativas nessa região para incentivar o rápido encaminhamento dos pacientes para diagnóstico e tratamento precoce. Abstract Introduction: Disorders of Sexual Development (DSD) result from an abnormal interaction of genetic and hormonal factors involved in determining embryonic development and sexual differentiation. Individuals with 46, XY karyotype who presented deficient virilization of the external genitalia are classified as having a syndrome of Sexual Development Disorder (46, XY DSD), including those between Androgen Insensitivity Syndrome (AIS). Several genes have been recognized for their participation in the formation of gonads and genitalia (internal and external) including the gene Androgen Receptor (AR). Objective: The aim of this study is to analyze the socio-epidemiological and clinical syndromic diagnosis of individuals with 46, XY disorders of sexual development (46, XY DSD) enrolled in the Genetics Clinic (C-HUPES-UFBA). Methods: we selected 13 patients with clinical diagnosis of AIS and traced the clinical and epidemiological profile. Results: Among the patients studied, 07 were diagnosed as CAIS and 06 as PAIS, and with the sex of rearing, respectively, the male and female and the average age at diagnosis was 06 years. About 38% had a positive family history. The most common reason for referral was hypospadias and ambiguous genitalia. The average length of falus was 2.77 cm. The most common location was the gonads in the scrotum. Only two patients had more than one hole perineal. Two patients received drug treatment and ten underwent corrective surgery of the genitalia. Conclusion: In this study population were diagnosed later, this requires social and educational actions in the region to encourage the rapid referral of patients for early diagnosis and treatment.

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Genetic Analysis for the Diagnosis of Disorders of Sexual Development in Indonesia

Journal of Biomedicine and Translational Research ◽

10.14710/jbtr.v2i2.622 ◽

2016 ◽

Vol 2 (2) ◽

pp. 44

Author(s):

Sultana MH Faradz

Keyword(s):

Sexual Development ◽

Disorders Of Sex Development ◽

External Genitalia ◽

Gonadal Development ◽

Androgen Insensitivity Syndrome ◽

Medical Professionals ◽

Adrenal Hyperplasia ◽

Disorders Of Sexual Development ◽

Sex Development

Disorders of sex development (DSD) is defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical, while in clinical practice this term means any abnormality of the external genitalia. DSD patients have been managed by a multidisciplinary gender team in our center as collaboration between Dr. Kariadi province referral hospital and Faculty of Medicine Diponegoro University. Diagnosis should be established by specific physical examination hormonal, chromosomal and DNA studies; and imaging for most of the cases depending on indication.Since 2004 the involvement of molecular and cytogenetic analysis so far can diagnosed many of the DSD cases. Most of the genetically proven cases were Congenital Adrenal hyperplasia, Androgen Insensitivity syndrome and sex chromosomal DSD that lead abnormal gonadal development. Many of them remain undiagnosed, further testing such as advanced DNA study should be carried out in collaboration with other center in overseas.The novel genes were found in some cases that contributed for the management of DSD. Information for medical professionals, patients, family members and community about the availability and necessity of DSD diagnosis should be delivered to improve DSD management and patient quality of life.

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Differences in sex development

10.1093/med/9780199682874.003.0114 ◽

2021 ◽

pp. 1313-1320

Author(s):

Dan Wood

Keyword(s):

Sexual Development ◽

Functional Outcomes ◽

External Genitalia ◽

Disorders Of Sexual Development ◽

Diagnosis And Management ◽

Sex Development ◽

Complex Group

Disorders of sexual development are a complex group of conditions with anomalies of the internal and external genitalia due to abnormal chromosomal and hormonal influences during development. Diagnosis and management, including timing of intervention, and both long-term cosmetic and functional outcomes are discussed in this chapter.

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Disorders of Sexual Development, Complete Androgen Insensitivity Syndrome (CAIS)

Encyclopedia of Pathology ◽

10.1007/978-3-030-41894-6_4805 ◽

2020 ◽

pp. 75-78

Author(s):

Manuel Nistal ◽

Pilar González-Peramato

Keyword(s):

Sexual Development ◽

Androgen Insensitivity Syndrome ◽

Disorders Of Sexual Development ◽

Complete Androgen Insensitivity Syndrome ◽

Androgen Insensitivity

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Male Fertility Is Compatible with an Arg840Cys Substitution in the AR in a Large Chinese Family Affected with Divergent Phenotypes of AR Insensitivity Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.87.1.8167 ◽

2002 ◽

Vol 87 (1) ◽

pp. 347-351 ◽

Cited By ~ 19

Author(s):

Jianhua Chu ◽

Rongmei Zhang ◽

Zhimin Zhao ◽

Wei Zou ◽

Yefei Han ◽

...

Keyword(s):

Sexual Development ◽

Male Fertility ◽

Genetic Disorder ◽

External Genitalia ◽

Mutant Gene ◽

Androgen Insensitivity Syndrome ◽

The Other ◽

Chinese Family ◽

Normal Range ◽

Androgen Insensitivity

Androgen insensitivity syndrome (AIS) is a disorder of male sexual development caused by an absent or dysfunctional AR. Fertile cases with mild AIS and slightly impaired AR activity had been reported in literature, and their external genitalia were documented to be usually normal or subnormal. We reported here an Arg840Cys substitution in the AR gene in a large Chinese pedigree affected with AIS. The mutant gene may result in infertility for some affected males with or without hypospadias. However, it was also observed that the mutation did not affect the fertility of the other patients. The gonadotropin levels for one of these patients were within the normal range. Thus, whether normal levels of the gonadotropins are necessary for the preserved fertility of patients affected with this genetic disorder remains to be elucidated.

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Histopathological spectrum of disorders of sexual development: a case series of seven cases

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20202283 ◽

2020 ◽

Vol 8 (6) ◽

pp. 2303

Author(s):

Saroj Ashok Bolde ◽

Arva Ali Pirosha ◽

Sushma N. Ramraje ◽

Shubhangi V. Agale

Keyword(s):

Sexual Development ◽

Genital Tract ◽

Gonadal Dysgenesis ◽

Case Series ◽

Androgen Insensitivity Syndrome ◽

Disorders Of Sexual Development ◽

Mrkh Syndrome ◽

Primary Amenorrhoea ◽

Derivatives Of ◽

Rule Out

Disorders of sexual development (DSD) refer to cases in which there is a discordance among at least two of the following; genetic sex, gonadal sex, genital tract sex and phenotypic sex. DSDs are quite rare with reported incidence varying from 1 in 4,500 to 1 in 5,500. Ovotesticular disorder is amongst the rarest variety of DSD comprising only to 3-10% of all cases of DSD with only 500 cases reported till now worldwide. Frequency of MRKH syndrome is 1 in 4,500 cases and is the cause of amenorrhoea in 15% of cases of primary amenorrhoea. Authors present a case series of seven cases of DSDs with three cases diagnosed as androgen insensitivity syndrome, two cases of true ovotesticular DSD (true hermaphrodite), one case each of mixed gonadal dysgenesis and Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome. Authors received the histopathology specimen of these cases in this department which was extensively sampled to study the gonads and the other derivatives of Mullerian and Wolffian duct and to rule out presence of any malignancy.

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Disorders of Sexual Development, Complete Androgen Insensitivity Syndrome (CAIS)

Encyclopedia of Pathology ◽

10.1007/978-3-319-28845-1_4805-1 ◽

2019 ◽

pp. 1-4

Author(s):

Manuel Nistal ◽

Pilar González-Peramato

Keyword(s):

Sexual Development ◽

Androgen Insensitivity Syndrome ◽

Disorders Of Sexual Development ◽

Complete Androgen Insensitivity Syndrome ◽

Androgen Insensitivity

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Paediatric endocrinology

10.1093/med/9780198851899.003.0007 ◽

2021 ◽

pp. 565-608

Author(s):

Ken Ong ◽

Emile Hendriks

Keyword(s):

Sexual Development ◽

Sexual Differentiation ◽

Secondary Growth ◽

Normal Growth ◽

Ambiguous Genitalia ◽

Hormone Deficiency ◽

Tall Stature ◽

Disorders Of Sexual Development ◽

Skeletal Dysplasias ◽

Paediatric Endocrinology

This chapter covers paediatric endocrinology. It starts with normal growth, then goes on to short stature, and constitutional delay of growth and puberty. Primary and secondary growth hormone deficiency are then explained, and treatment is outlined alongside GH resistance. It goes on to hypothyroidism, coeliac disease, skeletal dysplasias, and Turner syndrome. Small gestational age, and tall stature and rapid growth are all covered, alongside normal puberty, precocious puberty, and delayed or absent puberty. Normal sexual differentiation and disorders of sexual development and the assessment of ambiguous genitalia are included.

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Peculiarities of feminizing surgical correction in children with disorders of sexual development

Paediatric Surgery Ukraine ◽

10.15574/ps.2021.72.63 ◽

2021 ◽

pp. 63-68

Author(s):

A.R. Potsiurko ◽

◽

I.Ya. Hrymak ◽

N.V. Helner ◽

B.I. Hyzha ◽

...

Keyword(s):

Surgical Treatment ◽

Sexual Development ◽

External Genitalia ◽

Surgical Correction ◽

Urogenital Sinus ◽

Disorders Of Sexual Development ◽

External Urethral Sphincter ◽

Genesis 1 ◽

Genetic Examination ◽

Side Walls

Purpose – to analyze own results of surgical treatment of serious forms of disorders of sexual development (DSD) in children after feminizing surgeries. To define practical protocol guides on the choice of the type of surgical correction. Materials and methods. Over the past 5 years surgeons of Lviv regional paediatric clinical hospital «OHMATDYT» have examined 12 children with DSD, signs of hermaphroditism (intersex). After complex examination the following states were diagnosed: androgenital syndrome in 5 girls (referred for further treatment to Kyiv paediatric medical centres); true hermaphroditism – 1 child; mixed gonadal dysgenesis (MCG) – 3 children; female pseudohermaphroditism (without determining genesis) – 1 child; partial testicular feminization syndrome, Morris syndrome (male pseudohermaphroditism) – 2 children. In connection with marked masculinization of external genitalia two children with MCG and the girl with pseudohermaphroditism underwent feminizing surgery, namely genital zone reconstruction, mobilization and excision of urogenital sinus walls, excision of genital cavernous bodies (in children with MCG) with clitoroplasty, vulvoplasty with labioplasty and vaginoplasty. Children with Morris syndrome are being prepared to feminizing surgery. Results. Each child had a personal examination plan. Verification of a child’s state lasted from several weeks to 2–3 months. Children who underwent feminizing surgery did not have male structures and had relatively well-developed female structures. More «natural», less traumatizing correction was preformed for each specific case. In all children who underwent surgery vagina opened into urogenital sinus lower than external urethral sphincter, so there was no need to form front vagina wall (back and side walls were formed). Out of all children treated in our hospital gender was legally changed to the opposite. Conclusions. The birth of a child with DSD is a most challenging problem for parents, doctors, psychologists and social workers. Such states require complex examination. Children with severe hypospadias must undergo genetic examination. Statistic data and our own experience show higher frequency of feminizing surgeries in such cases. The most difficult part of such surgeries proves to be the excision of genital cavernous bodies with clitoroplasty and clitoris translocation; the most responsible part in functional sense is vaginoplasty. Surgical treatment is not the final stage of treatment for such patients. Children with DSD require constant further dynamic checkups by gynaecologists, urologists, oncologists, endocrinologists, psychologists with relevant therapy correction. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: disorders of sexual development (DSD), hermaphroditism, feminizing correction.

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Disorder Of Sex Development : Ambiguous Genitalia, Partial Androgen Insensitivity Syndrome

AVERROUS: Jurnal Kedokteran dan Kesehatan Malikussaleh ◽

10.29103/averrous.v3i2.432 ◽

2018 ◽

Vol 3 (2) ◽

pp. 1

Author(s):

Rajuddin Rajuddin ◽

Fauzan Fauzan

Keyword(s):

Disorders Of Sex Development ◽

External Genitalia ◽

Ambiguous Genitalia ◽

Androgen Insensitivity Syndrome ◽

Gender Assignment ◽

Androgen Insensitivity ◽

Sex Development ◽

Molecular Term ◽

Congenital Condition ◽

Partial Androgen Insensitivity Syndrome

Disorders of sex development (DSDs) also known as “intersex” are congenital condition by mismatch in which chromosomal, gonadal and anatomical. One in 4.500 infants is born with abnormalities of External genitalia, and mostly unexplained in molecular term. Androgen Insensitivity Syndrome (AIS) is a common cause of DSDs. Partial Androgen Insensitivity Syndrome (PAIS) is one of three broad subdivided phenotypes of AIS. Typically, characterized by evidence of feminization (i.e., undermasculinization) of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. In males characterized, Pais is common to observe a micropenis, hypospadias, and cryptorchidism. Individuals with PAIS that are characterized as women have been observe to have clitoromegaly and a fused labia during puberity . We reported a 13 year old child, with chief complaint primer amenorrhea. The patient admit as a girl but not yet got her menstruation. Patient was referred by Endocrinology Fertility and Reproductive Consultant of OBGYN, that has done Cromosomal and Hormonal analysis. We perform a laparascopy Exploratif and we get no uterus, fallopian tubal and ovarium that are exist. But, we found testis in inguinal canal. Decision regarding gender assignment are still confronted between patient”s Family and medical staff. The prognosis is depends on the ambiguity of genital, Physical, and Physicosocial adjustment for sex assignment.

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