Diagnosis Of Androgen Insensitivity Syndrome Research Articles

Early diagnosis of androgen insensitivity syndrome with cell-free fetal DNA screening: A case report.

SynopsisNon‐invasive prenatal testing provides an early opportunity to identify patients with genotype–phenotype sex discordance and can be used to screen for complete androgen insensitivity syndrome.

Clinical Case of the Complete Form of Androgen Insensitivity Syndrome (AIS)

The article presents a clinical observation of an extremely rare in gynecological practice androgen insensitivity syndrome (AIS). The authors give data on the pathogenesis of the disease, modern classification and terminology of various forms of this pathology. The phenotypic manifestations of the disease, the results of clinical and instrumental studies and surgical treatment are described.The results of the study show the possibility of clinical diagnosis of AIS and timely surgical treatment of patients with this pathology, due to the high risk of gonadal malignancy.

Incidental Inguinal Tubercular Lymphadenitis in a female of Androgen Insensivity Syndrome- A rarest of rare presentation

Androgen insensitivity syndrome (AIS) is a rare X-linked recessive disorder occurring in phenotypic women with male genotype (46, XY) resulting due to mutation in the X chromosome. On the other hand, tuberculosis (TB) is a chronic granulomatous infection caused by Mycobacterium tuberculosis, an acid-fast bacillus. We report a case of a 22-year-old unmarried female presenting with bilateral inguinal pain and primary amenorrhea, which, on comprehensive evaluation, revealed complete female external genitalia and intra-abdominal testes. The karyotype was 46 XY, hence a diagnosis of complete AIS was made. One of the ‘probable testes’ removed surgically was an inguinal lymph node with tuberculous lymphadenitis. Isolated inguinal tuberculous lymphadenopathy, by itself, is rare. Co-occurrence of Complete AIS and inguinal tuberculous lymphadenopathy is a highly unusual and rare association that has not been documented in the literature reviewed.

Novel pathogenic variants in the androgen receptor gene associated with androgen insensitivity syndrome identified through exome sequencing and in silico analysis

Androgen insensitivity syndrome (AIS) is a common disorder/differences of sex development with a 46, XY karyotype, but diverse genital phenotypes. Various pathogenic variants within the androgen receptor (AR) gene on the X chromosome are the primary pathogenesis of AIS. However, some patients with AIS still lack a definitive molecular diagnosis. Here, molecular diagnosis of eight patients with the clinical phenotype of AIS was performed using exome sequencing. We found eight variants of the AR gene, including p.(C131*), p.(W435*), p.(T653Lfs*8), c.2318+1G>T, p.(S397R), p.(Y572C), p.(S648G), and p.(D691G), and a pathogenic copy number variation covering a deletion of exon 2 of AR gene. Patient pedigree validation confirmed that the discovered variants conformed to the X-linked recessive inheritance patterns of AIS. In silico analysis indicated that the splice site variant (c.2318+1G>T) could lead to loss of the original 5′ splice donor site and exon skipping. Missense variants, including p.(S397R), p.(S648G), and p.(D691G), may affect the structure and function of the AR protein. Our results highlight the applicability of exome sequencing for molecular diagnosis of AIS. The novel variants found in this study enrich the pathogenic variant spectrum of the AR gene and provide a basis for the diagnosis and management of patients with AIS. A definite molecular diagnosis will provide accurate guidance for genetic counseling of proband’s family members.

Detection of c.G2194A mutation in \(\textit{AR}\) gene of a vietnamese patient with androgen insensitivity syndrome: a case report

Androgen insensitivity syndrome (AIS) is a rare X-linked recessive androgen receptor (AR) disorder. However, the overlap in clinical manifestations between AIS and other disorders of sex development can cause clinical diagnostic difficulties. Applying the whole coding region sequencing method is an optimal method for the diagnosis of AIS. In this study, whole-exome sequencing was performed to screen mutations in the AR gene as well as genes related to disorders of sex development (DSD). Sanger sequencing was applied to validate the mutations in the patient. One missense mutation in the AR gene which was reported previously was identified in the patient. In this site, nucleotide G is changed to A at position 2194 on cDNA (c.G2194A), leading to a substitution of aspartic at position 732 aspartic to asparagine (p.Asp732Asn). However, this is the first published case in a Vietnamese with this mutation. Our study expands the mutation spectrum of the AR gene in Vietnamese patients and confirms the usefulness of whole-exome sequencing in the diagnosis of AIS. The results of the study are the basis for supporting doctors in prenatal diagnosis and giving reasonable advice to patients and families.

PD02-12 THE RISK OF GONADAL MALIGNANCY IN PATIENTS WITH ANDROGEN INSENSITIVITY SYNDROME

You have accessJournal of UrologyCME1 May 2022PD02-12 THE RISK OF GONADAL MALIGNANCY IN PATIENTS WITH ANDROGEN INSENSITIVITY SYNDROME Pratik Kanabur, Soo Jeong Kim, Sagar Patel, Lefkothea Karaviti, and Paul F. Austin Pratik KanaburPratik Kanabur More articles by this author , Soo Jeong KimSoo Jeong Kim More articles by this author , Sagar PatelSagar Patel More articles by this author , Lefkothea KaravitiLefkothea Karaviti More articles by this author , and Paul F. AustinPaul F. Austin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002517.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen Insensitivity Syndrome (AIS) is a rare condition caused by a mutated androgen receptor, with varying penetrance levels. Patients often have undescended gonads, and thus an increased risk for developing germ cell tumors. Optimal gonad management in these patients is controversial. We aim to review the outcomes of gonad management in a large series of AIS patients at a single center. METHODS: A retrospective review was performed of patients with a diagnosis of AIS seen at a freestanding children’s hospital (2010-2020). Various patient factors including age at presentation, phenotypic gender, and subtype of AIS were collected. Management strategies including presence of imaging and tumor markers (AFP, HCG, LDH), surgical intervention, and length of follow-up were also evaluated. We also determined the rate of malignancy in gonadectomy specimens. RESULTS: 24 patients were included, 6 (25%) with partial AIS (PAIS) and 18 (75%) with complete AIS (CAIS). Age at evaluation ranged from 0 to 22 years. Of patients with PAIS, median age at presentation was 15 years. 3 (50%) had imaging of gonads and 2 (33%) had tumor markers obtained, all of which was negative for malignancy. 3 patients (50%) had surgical intervention (1 gonadopexy and 2 bilateral gonadectomy). One patient who underwent bilateral gonadectomy at 15 years of age was diagnosed with T1 dysgerminoma; there was no recurrence or progression of disease after 5 years of follow-up. Average length of follow-up was 2.9 years. Of patients with CAIS, median age at evaluation was 10.5 years. 12 (75%) had imaging of gonads and 3 (16.7%) had tumor markers obtained, all of which was negative for malignancy. 15 patients (83%) had surgical intervention (1 gonadopexy, 4 unilateral gonadectomy, 10 bilateral gonadectomy). One patient who underwent bilateral gonadectomy at 22 years of age had germ cell neoplasia in situ. She did not develop recurrence or progression after 6 years of follow-up. Average length of follow-up was 2.8 years. CONCLUSIONS: The majority of patients with CAIS and PAIS underwent surgical gonadectomy, and at younger ages (<5). In patients who had a gonadectomy after 12 years of age, over 25% of patients had a malignancy in the specimen, but were able to be treated with surgery alone. Imaging and tumor markers did not diagnose any malignancies. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e40 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pratik Kanabur More articles by this author Soo Jeong Kim More articles by this author Sagar Patel More articles by this author Lefkothea Karaviti More articles by this author Paul F. Austin More articles by this author Expand All Advertisement PDF DownloadLoading ...

Clinical, Biochemical, and Molecular Characterization of Indian Children with Clinically Suspected Androgen Insensitivity Syndrome

This study describes the clinical, biochemical, and molecular characteristics of Indian children with 46,XY DSD and suspected androgen insensitivity syndrome (AIS). Fifty children (median age 3.0 years, range 0–16.5 years) with 46,XY DSD and a suspected diagnosis of AIS were enrolled. Sanger sequencing was performed to identify pathogenic variants in the androgen receptor (AR) gene and to study genotype-phenotype correlations. All 5 (100%) patients with CAIS and 14/45 (31%) patients with PAIS had pathogenic/likely pathogenic variants in the AR gene (overall, 14 different variants in 19 patients; 38.8%). There was no significant difference in clinical (cryptorchidism, hypospadias, or external masculinizing score) or biochemical parameters (gonadotropins and testosterone) between patients with or without pathogenic variants. However, patients with AIS were more likely to have a positive family history, be assigned female gender at birth, and present with gynaecomastia at puberty. Three novel pathogenic/likely pathogenic variants, including one splice donor site variant c.2318+1G>A, one frameshift variant p.H790Lfs*40, and one missense variant p.G821E, were identified in 3 patients with CAIS. The missense variant p.G821E was predicted as deleterious, damaging, disease-causing, and likely functionally inactive by in silico analysis and protein modelling study. Two previously not reported pathogenic/likely pathogenic variants, including p.R386H and p.G396R, were identified in patients with PAIS. This study contributes in expanding the spectrum of pathogenic variants in the AR gene in patients with AIS. Only 31% patients with a provisional diagnosis of PAIS had pathogenic variants in the AR gene, suggesting other possible mechanisms or candidate genes may be responsible for such a phenotypic presentation.

The challenges of androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling.

Analysis of the androgen receptor (AR) gene in a cohort of Indonesian undermasculinized 46, XY DSD patients

BackgroundPathogenic variants in the androgen receptor (AR) gene located on chromosome Xq11-12, are known to cause varying degrees of undermasculinization in 46, XY individuals. The aim of this study was to investigate the frequency of pathogenic variants in the AR gene in a cohort of 46, XY undermasculinized individuals from Indonesia who were suspected of having androgen insensitivity syndrome (AIS). All patients with 46, XY DSD referred to our center between 1994 and 2019 were collected from our clinical database. All 46, XY DSD patients without a prior molecular diagnosis with an external masculinization score (EMS) ≤ 9 were included in this study. All exons and intron–exon boundaries of AR gene were analyzed using Sanger sequencing to identify pathogenic variants of the AR gene.ResultsA cohort of 75 undermasculinized patients were selected for the study. Direct Sanger sequencing of all eight exons of the AR gene led to a genetic diagnosis in 11 patients (14.67%). All of the variants identified (p.Arg841His; p.Ile604Asn; p.Val731Met; p.Pro672Ser; p.Gln739Arg; p.Ser302Glufs*3) have been previously reported in patients with AIS.ConclusionsThis is the first study in Indonesia that highlights the significance of molecular analysis in providing a definitive diagnosis of AIS for patients with 46, XY DSD undermasculinization. This is an uncommon finding in the Indonesian population presenting with 46, XY DSD undermasculinization. A genetic diagnosis allows optimal clinical management and genetic counseling for patients and their families. As 46, XY DSD can be caused by pathogenic variants in other genes involved in gonadal development and differentiation, further genetic analysis, such as whole exome sequencing, should be carried out on those patients that did not carry an AR variant.

Clinical, hormonal and genetic characteristics of androgen insensitivity syndrome in 39 Chinese patients

BackgroundAbnormal androgen receptor (AR) genes can cause androgen insensitivity syndrome (AIS), and AIS can be classified into complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS) and mild AIS. We investigated the characteristics of clinical manifestations, serum sex hormone levels and AR gene mutations of 39 AIS patients, which provided deeper insight into this disease.MethodsWe prospectively evaluated 39 patients with 46, XY disorders of sex development (46, XY DSD) who were diagnosed with AIS at the Department of Endocrinology of Shanghai Children’s Hospital from 2014 to 2019. We analysed clinical data from the patients including hormone levels and AR gene sequences. Furthermore, we screened the AR gene sequences of the 39 AIS patients to identify probable mutations.ResultsThe 39 AIS patients came from 37 different families; 19 of the patients presented CAIS, and 20 of them presented PAIS. The CAIS patients exhibited a higher cryptorchidism rate than the PAIS (100 and 55%, P = 0.001). There were no significant difference between the CAIS and PAIS groups regarding the levels of inhibin B (INHB), sex hormone-binding globulin (SHBG), basal luteinizing hormone (LH), testosterone (T), or basal dihydrotestosterone (DHT), the T:DHT ratio, DHT levels after human chorionic gonadotropin (HCG) stimulation or T levels after HCG stimulation. However, the hormone levels of AMH (P = 0.010), peak LH (P = 0.033), basal FSH (P = 0.009) and peak FSH (P = 0.033) showed significant differences between the CAIS group and the PAIS group. Twenty-one reported pathogenic and 9 novel AR mutations were identified. Spontaneous AR mutations were found in 5 AIS patients, and 21 patients inherited mutations from their mothers, who carried heterozygous mutations.ConclusionsForty-six XY DSD patients with cryptorchidism and female phenotypes were highly suspected of having AIS. We demonstrated that CAIS patients could not be distinguished by their hormone levels alone. Compared with PAIS patients, CAIS patients exhibited higher basal FSH, peak FSH, and peak LH hormone levels but lower AMH expression. We identified 21 reported pathogenic AR mutations and 9 novel AR mutations that led to different types of AIS. Missense mutations were the major cause of AIS and mostly occurred in exon 7 of the AR gene. These findings provided deeper insight into the diagnosis and classification of AIS and will even contributed to its clinical assessment.

"Spectrum of 46 XY Disorders of Sex Development": A Hospital-based Cross-sectional Study.

Background:Disorders of sex development (DSD) are a wide range of relatively rare conditions having diverse pathophysiology. Identification of an underlying cause can help in treating any coexisting hormone deficiencies and can help with anticipating any other immediate or long-term health concerns.Objective:To study the clinical and biochemical profile of patients with 46 XY DSD along with androgen receptor (AR) gene mutation status in selected group of patients.Methods:A cross-sectional study was conducted after enrolling the eligible DSD patients. Thorough elicitation of history and detailed clinical examination was done. Assays for luteinizing hormone, follicle-stimulating hormone, testosterone, dihydrotestosterone, androstenedione, AMH & Inhibin B (where indicated), and human chorionic gonadotropin stimulation were done as per protocol.Results:In total, 48 patients were included in the study. Ambiguous genitalia (58.3%) followed by hypospadias (33.3%) were common presentation. Androgen biosynthetic defect were the most commonly encountered diagnosis followed by androgen insensitivity syndrome (AIS). Swyer syndrome was diagnosed in 4.2% of cases; partial gonadal dysgenesis, ovotesticular DSD, and vanishing testis syndrome contributed to 2% of cases each. Eight cases (16.7%) who presented with isolated proximal and midshaft hypospadias for whom no diagnosis was found were categorized in the “etiology unclear” group. AR gene mutation analysis designed against specific exons did not yield any results.Conclusion:46 XY DSD is a heterogeneous group of patients with a varying age of presentation and a diverse clinical profile. Most patients are reared as males and maintained the same gender identity except in isolated cases. Diagnosis of AIS remains a clinical challenge as a definite hormonal criterion does not exist and genetic mutations in AR gene may be negative. Flanking region sequencing, whole genome sequencing, and promoter region sequencing may reveal pathogenic variants. Variations in other genes regulating AR pathway may also be candidates to be studied.

Phenotypic and molecular characteristics of androgen insensitivity syndrome patients.

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.

Mutational analysis of the androgen receptor (NR3C4) gene in patients with 46,XY DSD

Androgen insensitivity syndrome (AIS) is an X-linked disorder caused by mutations in the NR3C4 gene, which encodes the androgen receptor (AR). In this study, we performed mutational analyses to identify AR molecular defects, in individuals with 46,XY disorders of sex development (46,XY DSD) and a presumptive diagnosis of AIS. Eighteen different gene mutations, including seven previously unreported new variants, were detected in 26 unrelated cases. These included two deletion mutations (P49fs*185 and E308f*320) in exon 1 and five substitution mutations (p.S792P, p.D829G, p.R832P, p.L839F, and p.K906E) located in the steroid-binding domain. Expression analyses of mutants generated by site-directed mutagenesis indicated that these new gene variants impaired AR function by affecting its binding activity. Seventeen of 18 mutations likely lead to reduced or absent responses to androgens, which may in turn account for the different degrees of undermasculinization observed. Our study provides insight into the functional consequences of these mutations.

Androgen Insensitivity Syndrome (AIS): A Case History

Androgen Insensitivity Syndrome (AIS) is an inherited X-linked recessive disease with a mutation in the Androgen Receptor (AR) gene resulting in - functioning of Y sex chromosome and abnormality on X sex chromosome, where affected individuals have male chromosomes and male gonads with complete or partial feminization of the external genitals. Recently a case of complete Androgen Insensitivity Syndrome (CAIS) is reported at Shaheed Suhrawardy Medical College, Dhaka. A 15 years old school girl was admitted with primary amenorrhea with bilateral inguinal hernia. Diagnosis of complete AIS is confirmed by discovering an adult male testosterone level, 46, XY karyotype, absence of axillary and pubic hair and a shallow vagina, with no cervix or uterus.&#x0D; Ibrahim Cardiac Med J 2014; 4(1): 33-37

Next generation sequencing and functional characterization of the androgen receptor (AR) gene in patients with androgen insensitivity syndrome (AIS) and controls

Androgen insensitivity syndrome (AIS) is characterized by a partial to complete lack of genital virilization in genetically male individuals. It is classically caused by inactivating mutations in the coding region of the X-chromosomal androgen receptor (AR) gene. However, up to two-third of the patients with a clinically established diagnosis of AIS lack a detectable molecular cause to date. As conventional sequencing is restricted to the AR coding exons, we set up a next generation sequencing (NGS) approach of the entire AR-gene locus for a comprehensive AR mutation analysis in patients with AIS. To this purpose, DNA was extracted from cultured genital skin fibroblasts (GSF = scrotum, foreskin, labia) of 80 patients with known and presumed AIS, two patients with 17sHSDIII deficiency, six patients with 5alpha-reductase deficiency and 15 control males. Patients were suspected to have AIS based on clinical findings, pathological androgen binding, reduced AR expression in GSF or a combination of these. The AR-sequencing library was produced using a capture-based method (Haloplex; Agilent). The target sequence included the coding region, the UTRs, 90% of the intron sequences as well as a 9kb upstream and 5kb downstream sequence. Sequencing was performed on a Miseq benchtop sequencer (Illumina). Alignment to the hg19 reference genome and single nucleotide polymorphism (SNP) calling was performed by the MiSeq-Reporter software (Illumina). Targeted NGS confirmed AR mutations in all patients with mutations previously identified by Sanger sequencing. Additional SNPs were detected in and outside the AR-coding region. In order to understand the functional impact of the SNPs, they were further tested for the ability of the endogenous AR to induce transcription of the AR target gene Apolipoprotein D (APOD-Assay). In conclusion we show that NGS is a valid method for AR-sequencing in presumed AIS and allows in combination with the APOD-Assay a refined classification of AIS.

L712V mutation in the androgen receptor gene causes complete androgen insensitivity syndrome due to severe loss of androgen function

Inability to respond to the circulating androgens is named as androgen insensitivity syndrome (AIS). Mutations in the androgen receptor (AR) gene are the most common cause of AIS. A cause and effect relationship between some of these mutations and the AIS phenotype has been proven by in vitro studies. Several other mutations have been identified, but need to be functionally validated for pathogenicity. Screening of the AR mutations upon presumptive diagnosis of AIS is recommended. We analyzed a case of complete androgen insensitivity syndrome (CAIS) for mutations in the AR gene. Sequencing of the entire coding region revealed C>G mutation (CTT–GTT) at codon 712 (position according to the NCBI database) in exon 4 of the gene, resulting in replacement of leucine with valine in the ligand-binding domain of the AR protein. No incidence of this mutation was observed in 230 normal male individuals analyzed for comparison. In vitro androgen binding and transactivation assays using mutant clone showed approximately 71% loss of ligand binding and about 76% loss of transactivation function. We conclude that CAIS in this individual was due to L712V substitution in the androgen receptor protein.

Androgen Insensitivity Syndrome with Gynandroblastoma and Vulvar Leiomyoma

This study aimed to describe a rare case of androgen insensitivity syndrome (AIS) in association with gynandroblastoma and vulvar leiomyomata. The patient was a 64-year-old phenotypically female person with 46 XY chromosomal karyotypes who presented with a chief complaint of abdominal distension of 1-month duration. She had 2 vulvar masses for more than 20 years and had experienced life-long (untreated) amenorrhea. History and physical examination findings showed the patient to be 175 cm in height, with normal breast development, and a lack of pubic or axillary hair. Serum levels were as follows: testosterone, 1,980 ng/dL; estradiol, 1,380.8 pg/mL. In combination with clinical findings, a diagnosis of complete AIS was made. The patient subsequently underwent surgery, during which the bilateral vulvar masses and the rudimentary uterus, right sex gland, and left side of the tumor were resected. Histological examination of the tumor revealed a mass composed primarily of juvenile-type granulosa cells, admixed with a Sertoli cell component that comprised less than 50% of the tumor. The right side of the gonad had an ovarian-like cortex and was considered to be an undeveloped ovary. The left and right side of the vulvar masses were diagnosed with leiomyomas. Patients with AIS should be monitored closely because these patients may also experience gonadal tumors. When confronted with gynandroblastoma, close attention should be paid to the patient's endocrinologic status, and comprehensive endocrinologic analyses should be conducted to make correct treatment decisions.

Community screening leading to the diagnosis of androgen insensitivity syndrome at the age of 65

Androgen insensitivity syndrome (AIS) is a disease that can be X-linked recessive or sporadic in nature. Patients with complete AIS are phenotypically female individuals with an XY genotype. During embryonic development, the testicular tissue present in patients with AIS produces Mullerian Inhibiting Substance, which blocks the development of the upper one third of the vagina, uterus and ovaries, while a lack of androgen receptors results in female-appearing external genitalia. Complete AIS patients tend to present as amenorrheic females during adolescence. This case report presents a unique situation in which a public health screening campaign, for abdominal aortic aneurysms, led to an incidental finding and work-up resulting in two separate, yet related diagnoses: androgen insensitivity syndrome (AIS) and sertoli cell adenoma. This case also highlights the importance of a comprehensive physical examination with emphasis on wide differential diagnosis. It underscores the importance of considering the complicated ethics surrounding patient disclosure when dealing with a sensitive diagnosis.

Challenges in clinical and laboratory diagnosis of androgen insensitivity syndrome: a case report

IntroductionAndrogen is a generic term usually applied to describe a group of sex steroid hormones. Androgens are responsible for male sex differentiation during embryogenesis at the sixth or seventh week of gestation, triggering the development of the testes and penis in male fetuses, and are directed by the testicular determining factor: the gene SRY (sex determining region on Y chromosome) located on the short arm of chromosome Y. The differentiation of male external genitalia (penis, scrotum and penile urethra) occurs between the 9th and 13th weeks of pregnancy and requires adequate concentration of testosterone and the conversion of this to another more potent androgen, dihydrotestosterone, through the action of 5α-reductase in target tissues.Case presentationThis report describes the case of a teenage girl presenting with a male karyotype, and aims to determine the extension of the mutation that affected the AR gene. A Caucasian girl aged 15 was referred to our laboratory for genetic testing due to primary amenorrhea. Physical examination, karyotype testing and molecular analysis of the androgen receptor were critical in making the correct diagnosis of complete androgen insensitivity syndrome.ConclusionsSex determination and differentiation depend on a cascade of events that begins with the establishment of chromosomal sex at fertilization and ends with sexual maturation at puberty, subsequently leading to fertility. Mutations affecting the AR gene may cause either complete or partial androgen insensitivity syndrome. The case reported here is consistent with complete androgen insensitivity syndrome, misdiagnosed at birth, and consequently our patient was raised both socially and educationally as a female. It is critical that health care providers understand the importance of properly diagnosing a newborn manifesting ambiguous genitalia. Furthermore, a child with a pseudohermaphrodite phenotype should always undergo adequate endocrine and genetic testing to reach a conclusive diagnosis before gender is assigned and surgical interventions are carried out. Our results show that extreme care must be taken in selecting the genetic tools that are utilized for the diagnosis for androgen insensitivity syndrome.

Bilateral Gonadal Cysts and Late Diagnosis of Androgen Insensitivity Syndrome Treated by Laparoscopic Gonadectomy

Background. Complete androgen insensitivity syndrome is a rare syndrome in which the uterus is absent and testes rather than ovaries are present. Patients usually visit a gynecologist due to primary amenorrhea. Case. A forty-eight-year-old woman with lower abdominal pain and anamnesis of uterus agenesis was operated on due to bilateral cystic masses. A 5 × 3 × 1.2 cm left adnexal cyst revealed the presence of a serous cyst with a hypoplastic ductus deferens. A smaller cyst of the right adnexa revealed immature testis tissue with Leydig-cell hyperplasia. After karyotype and hormonal examinations, laparoscopic gonadectomy was performed. Conclusion. Attention should be paid in all cyst-removing operations in cases of uterus agenesis, due to the high incidence of malignancy. Not of less importance is the issue of informing the patient in the most appropriate way.