Complete Androgen Insensitivity Syndrome: From Bench to Bed (original) (raw)
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Androgen Insensitivity Syndrome: A rare genetic disorder
International Journal of Surgery Case Reports, 2020
BACKGROUND: Androgen Insensitivity Syndrome (AIS) is a rare X-linked recessive androgen receptor (AR) disorder with 46XY karyotype. Partial AIS affects 5-7 per 1,000,000 genetically male individuals whereas Complete AIS affects 2-5 per 100,000 genetically male individuals. CAIS CAIS is characterized by complete resistance to the action of androgens. PRESENTATION OF CASE: 17-year patient presented with swelling in bilateral inguinal region. Patient also complained of primary amenorrhea with serum FSH and LH levels being raised, serum testosterone level much above normal range. MRI Pelvis revealed agenesis of vagina, uterine body, both ovaries and cervix. Bilateral testes were noted in bilateral superficial inguinal ring. Bilateral orchidectomy was done and the patient was advised estrogen substitution therapy. DISCUSSION: CAIS is usually diagnosed at puberty, when the patient presents with primary amenorrhea. Karyotype has to be mapped in order to differentiate from other genetic disorders. Orchidectomy should be done to avoid risk of malignancy of undescended intra-abdominal testes (3.6 % at 25 years old, and 33 % at 50 years old, reported by various studies). Hormonal substitution therapy should be administered. Comprehensive psychiatric assessment and intervention go a long way in alleviating distress and enhancing quality of life. CONCLUSION: Androgen Insensitivity Syndrome requires expert and sympathetic handling. Close collaboration between surgeon, gynaecologist and psychologist is essential for proper management of complete androgen insensitivity syndrome.
Androgen insensitivity syndrome: clinical features and molecular defects
HORMONES, 2008
The end-organ resistance to androgens has been designated as Androgen Insensitivity Syndrome (AIS), an X-linked disorder caused by mutations in the Androgen Receptor (AR) gene. It is generally accepted that defects in the AR gene prevent the normal development of both internal and external genital structures in 46,XY individuals, causing a variety of phenotypes ranging from male infertility to completely normal female external genitalia. Precise diagnosis requires clinical, hormonal and molecular investigation and is of great importance for appropriate gender assignment and management in general. The complexity of phenotypic presentation of AIS with genotype-phenotype variability of identical mutations complicates both the diagnostic procedure and genetic counseling of the affected families. More than 400 different AR gene mutations have thus far been reported but the receptor structure-function relationship and its phenotypic outcome is not yet fully understood. This review focuses on the clinical features and molecular pathophysiology of AIS and explores the relationship of the molecular defects in the AR gene to their clinical expression.
The Journal of Clinical Endocrinology & Metabolism, 2000
Androgen insensitivity syndrome (AIS) is the most common single entity that results in male under-masculinization, but large cohort studies of AIS have rarely been performed. Over the last decade, nationwide cooperation between pediatric endocrinologists in the United Kingdom has allowed the creation of a database of cases of intersex and ambiguous genitalia where detailed clinical information on every notified case has been collected via a questionnaire. Among the 816 entries recorded by January 1999, there were 105 clinically diagnosed cases of complete AIS (CAIS) and 173 cases of partial AIS (PAIS). A masculinization score was devised by scoring the external phenotype, and a score of 12 represented normal masculinization. Androgen receptor (AR) binding was determined by studying binding capacity (B max) and receptor affinity (K d), and cases were classified as either zero, abnormal, or normal binding. Mutation screening of all eight exons of the AR gene was performed by single-strand conformational polymorphism analysis, followed by direct DNA sequencing. All cases of PAIS presented within the first month of birth. The median age at presentation of children with CAIS was 1 yr (P10,P90: 0.1,10.4). The testes were palpable in the labioscrotal folds or the inguinal region in 77% and 41% of cases of CAIS and PAIS, respectively. There was marked overlap between the masculinization score of those children with PAIS reared as girls [2.5(P10,P90:1, 6)] and those reared as boys [3(P10,P90:2, 7.5)]. Gonadectomy was performed prepubertally in 66% and postpubertally in 29% of the cases of CAIS.
Androgen insensitivity syndrome: a review
Archives of endocrinology and metabolism
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.
Androgen insensitivity syndrome
The Lancet, 2012
Androgen insensitivity syndrome in its complete form is a disorder of hormone resistance characterised by a female phenotype in an individual with an XY karyotype and testes producing age-appropriate normal concen trations of androgens. Pathogenesis is the result of mutations in the X-linked androgen receptor gene, which encodes for the ligand-activated androgen receptor-a transcription factor and member of the nuclear receptor superfamily. This Seminar describes the clinical manifestations of androgen insensitivity syndrome from infancy to adulthood, reviews the mechanism of androgen action, and shows examples of how mutations of the androgen receptor gene cause the syndrome. Management of androgen insensitivity syndrome should be undertaken by a multidisciplinary team and include gonadectomy to avoid gonad tumours in later life, appropriate sex-hormone replacement at puberty and beyond, and an emphasis on openness in disclosure.
Complete androgen insensitivity syndrome--a review
Journal of Pediatric and …, 2008
This review paper highlights important diagnostic and therapeutic concerns for girls with Complete Androgen Insensitivity Syndrome (CAIS). CAIS is an androgen receptor defect disorder associated with vaginal and uterine agenesis in women with a 46,XY karyotype. The major clinical issues surrounding this syndrome include timing of gonadectomy, hormone replacement, vaginal dilation, and attention to psychological issues.
46 XY, Female. Complete androgen insensitivity syndrome: a case report
Journal of Education, Health and Sport
Introduction: Androgen insensitivity syndrome (AIS) is an inherited disorder of sexual development caused by mutations in the androgen receptor encoding gene. Case report: A female patient born in 1984, at the age of 17, was diagnosed with complete androgen insensitivity syndrome, during the diagnosis of primary amenorrhea. She was assigned grade 7 in the Quigley scale. Cytogenetic analysis showed a 46 XY karyotype. Gynecological examination revealed a blind ending vagina and a lack of uterus. Physical examination revealed normal breast development and scanty pubic and axillary hair. The patient kept seeing herself as a woman. At the age of 18, the patient underwent laparoscopic gonadectomy. After the procedure, the patient was under medical supervision and was taking orally 1 mg of estradiol daily. At the age of 24 patient was diagnosed with. The patient received sodium alendronate and ibandronic acid. The level of FSH was 35.50 mlU / ml and LH was 13.05 mlU/ml. Discussion: Quigley...
Complete androgen insensitivity syndrome in three sisters: A case report
Journal of Turkish Society of Obstetric and Gynecology, 2014
Complete androgen insensitivity syndrome (CAIS) (testicular feminization) is the most common cause of male pseudohermaphroditism. The underlying main pathology is an end organ resistance to androgen stimulation, and as a result, this impairs the differentiation of the body structures and systems which this hormone affects. Inheritance of this disorder is by means of an X-linked recessive gene that is responsible for the intracellular androgen receptors. CAIS may be observed in several members of a family. For this reason, the family members of the affected individual should be screened. In this article we present a case of three sisters diagnosed with CAIS after investigating the pedigree of one of them owing to an inguinal mass and diagnosing with CAIS.