Complete Androgen Insensitivity Syndrome: From Bench to Bed

Abstract

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS.

Complete Androgen Insensitivity Syndrome: From the Relevance of an Accurate Genetic Diagnosis to the Challenge of Clinical Management. A Case Report

“…Another important question regards hormonal replacement therapy (HRT), which is fundamental in patients with CAIS after bilateral gonadectomy. The classic HRT for patients with CAIS is based on estrogen administration, although there are no clear guidelines on hormone formulation, dosages, and monitoring [9]. Despite good compliance to HRT, many patients with CAIS report decreased well-being and sexual satisfaction [19,20].…”

“…The majority of the AR variants have been discovered in the LBD region that can alter several functions of the receptor, such as its ligand-binding ability and the interplay with other coactivators [1]. In about two-thirds of the cases, variants in the AR gene originate from germ cells of asymptomatic mothers, whereas in other cases, they originate in somatic cells or are de novo variants [9].…”

Late Diagnosis of Partial Androgen Insensitivity Syndrome in a Peruvian Child

“…Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder, which is the main disorder of sexual development (DSD) in a patient with a 46 XY karyotype; its prevalence is 1:20,000-1:100,000 births [4]. It is the result of alterations in the androgen receptor gene, leading to a framework of hormonal resistance, which can present clinically in three phenotypes, namely, complete, mild, or partial [5], according to the degree of female phenotype, given the resistance to the biological actions of androgens in male with this karyotype with a normal testicle function and normal concentrations of androgen by age [6].…”

Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis

“…Moreover, the repair of DNA damage could be affected by androgen signaling by regulating gene expression and transcription-related processes (8). Therefore, defects in AR could compromise the virilization process, exhibiting variably impaired masculinization of external genitalia, spermatogenesis arrest, gynecomastia, sparseness or absence of pubic and axillary hair, increased risk of gonadal tumors, and abnormal sex hormone levels (9). However, this disorder also leads to abnormal symptoms of other systems in males: slightly increased height as compared with normal females, disorder of skeletal development, inherited X-linked neurodegenerative disease, increased incidence of insulin resistance and cardiovascular risk, and risk of infection and autoimmune diseases were reported in CAIS and aromatase knockout (ARKO) mice (7,(10)(11)(12)(13).…”