Materiały źródłowe

• #1 Androgen Insensitivity Syndrome – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1429/

  The diagnosis of AIS is established in an individual with a 46,XY karyotype who has: undermasculinization of the external genitalia, impaired spermatogenesis with otherwise normal testes, absent or rudimentary mullerian structures, evidence of normal or increased synthesis of testosterone and its normal conversion to dihydrotestosterone, and normal or increased luteinizing hormone (LH) production by the pituitary gland; AND/OR a hemizygous pathogenic variant in AR identified by molecular genetic testing. […] The diagnosis of AIS is established in a 46,XY proband with: […] A hemizygous pathogenic (or likely pathogenic) variant in AR identified by molecular genetic testing. […] No formal diagnostic criteria for identifying AIS have as yet been published; large variance is seen at the molecular, biochemical, and morphologic levels due to the extreme variation in these characteristics with the various AIS phenotypes.

• #1

  https://www.nhs.uk/conditions/androgen-insensitivity-syndrome/

  Androgen insensitivity syndrome (AIS) affects the development of a person’s genitals and reproductive organs. […] CAIS can be more difficult to spot, as the genitals usually look like those of any other girl. It’s often not diagnosed until puberty, when periods do not start and pubic and underarm hair does not develop. […] Read more about the symptoms of AIS and diagnosing AIS. […] You and your child will be offered psychological support to help you understand and cope with the diagnosis of AIS.

• #2 Androgen Insensitivity Syndrome: Complete & Partial

  https://my.clevelandclinic.org/health/diseases/22199-androgen-insensitivity-syndrome

  Androgen insensitivity syndrome (AIS) is a rare, inherited, sexual development disorder. […] AIS can cause problems during puberty, as well as infertility. […] AIS prevents male genitals from developing as they should. It almost always results in infertility during adulthood. […] A healthcare provider can often diagnose PAIS right after birth by looking at a babys genitals. But CAIS or MAIS might not be evident until the age of 11 or 12 when puberty begins. […] Your healthcare provider will need to do tests to confirm a diagnosis: Blood tests check hormone levels, sex chromosomes and genetic abnormalities. Imaging exams, such as ultrasound, can confirm the absence of female reproductive organs. […] Treatment for AIS depends on sex, which is recorded for an infant at birth. […] But some health experts think certain treatments, such as removal of the testicles, should happen before puberty.

• #3 Androgen Insensitivity Syndrome | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/androgen-insensitivity-syndrome

  Complete androgen insensitivity syndrome may be discovered in infancy when a testicle is felt as a mass in the groin or abdomen. However, in most cases, the syndrome isnt diagnosed until adolescence or later. […] Partial androgen insensitivity may be diagnosed at birth because of the presence of male and female sexual traits. […] Tests used to confirm this condition include blood work to check hormone levels, genetic testing and pelvic ultrasound.

• #4

  https://www.archivesofmedicalscience.com/The-challenges-of-androgen-insensitivity-syndrome,125584,0,2.html

  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. […] 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. […] In order to confirm the diagnosis, a karyotype assessment should be considered. Imaging investigations, readily available, reveal the absence of the uterus, fallopian tubes and ovaries and the presence of testes. […] The diagnosis in patients with mild AIS is made usually during adulthood due to infertility or during puberty due to the development of gynecomastia, whereas in patients with complete androgen insensitivity the diagnosis can be made during pregnancy, at birth, during childhood or adulthood.

• #4

  https://www.archivesofmedicalscience.com/The-challenges-of-androgen-insensitivity-syndrome,125584,0,2.html

  For cases with PAIS, the diagnosis is made in most cases at birth due to the presence of ambiguous genitalia. […] The management of AIS requires a multidisciplinary team of paediatricians, endocrinologists, gynaecologists, urologists, plastic surgeons and psychiatrists. Psychological counselling should be recommended for these patients and their parents.

• #5 Androgen Insensitivity: Symptoms, Causes, and Treatment

  https://www.verywellhealth.com/androgen-insensitivity-4173975

  The initial diagnosis of androgen insensitivity is usually because of symptoms. […] Often, complete androgen insensitivity is not diagnosed until puberty. Lack of menstruation blood in combination with normal breast growth and a lack of pubic and underarm hair should cause doctors to suspect CAIS. […] Lack of menstruation blood can also be the trigger for doctors to identify that a young woman does not have a uterus on an ultrasound or other exams. […] Partial androgen insensitivity may be diagnosed much earlier. If the genitals are clearly ambiguous at the time of birth, a number of tests may be done. These include a karyotype or a count of the chromosomes. Hormone levels may also be tested. In adult men, a semen analysis may be done. […] At the time of birth, testosterone and luteinizing hormone (LH) levels are low, and later on they increase. During puberty, testosterone and LH levels are usually normal or slightly elevated for individuals with PAIS. However, individuals with CAIS will have very high levels. This is because hormone production is controlled by negative feedback loops. In individuals with CAIS, there is no mechanism for feedback.

• #6 Androgen Insensitivity | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/androgen-insensitivity

  How is androgen insensitivity diagnosed? Complete androgen insensitivity is usually not diagnosed before puberty, unless a lump is felt in the groin or abdomen, and it turns out to be a testicle during surgery. Usually, androgen insensitivity is diagnosed only after a young woman discovers that she hasn’t started menstruation. […] A physician may use the following diagnostic tests to diagnose androgen insensitivity: genetic testing, blood work to check the levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), pelvic ultrasound.

• #7

  https://www.nhs.uk/conditions/androgen-insensitivity-syndrome/diagnosis/

  An ultrasound scan can also be used to confirm the absence of the womb and ovaries. […] If a surgeon thinks they’ve found testicles in a baby’s tummy during a hernia repair operation, a small tissue sample (biopsy) may be taken and analysed to confirm they are testicles and not ovaries. […] Testing can also be carried out in unborn babies when there’s a known family history of AIS. […] There are 2 main tests that can be carried out during pregnancy to determine whether a baby has AIS: chorionic villus sampling (CVS) a sample of cells is removed from the placenta for testing, usually with a needle; this is usually carried out between week 11 and week 14 of pregnancy. […] amniocentesis a needle is used to extract a sample of the fluid surrounding the baby (amniotic fluid) for testing; this is usually carried out between week 15 and week 20 of pregnancy.

• #8 Androgen Insensitivity Syndrome Workup: Laboratory Studies, Imaging Studies, Histologic Findings

  https://emedicine.medscape.com/article/924996-workup

  The studies described below may be indicated in patients with androgen insensitivity syndrome (AIS). […] A karyotype is essential to differentiate an undermasculinized male from a masculinized female. Alternatively, the presence of a Y chromosome can be confirmed by fluorescent in situ hybridization (FISH) probes for either the SRY region of the Y chromosome or a subtelomeric Y chromosome probe. These offer a much quicker turnaround time than conventional karyotypes. […] Levels of testosterone and dihydrotestosterone (DHT) establish the presence of normal steroidogenesis. If the testosterone level is low for age, obtain levels of dehydroepiandrosterone (DHEA), androstenedione, and their precursors, 17-hydroxypregnenolone and 17-hydroxyprogesterone. These levels allow identification of errors in the steroid biosynthetic pathways. An elevated ratio of testosterone to DHT indicates a 5-alpha reductase deficiency, a possible differential for patients with partial androgen insensitivity syndrome but usually not for complete androgen insensitivity syndrome. Low levels of testosterone in the absence of evidence of defective steroidogenesis suggest testicular dysgenesis or Leydig cell aplasia/hypoplasia.

• #8 Androgen Insensitivity Syndrome Workup: Laboratory Studies, Imaging Studies, Histologic Findings

  https://emedicine.medscape.com/article/924996-workup

  Mutation analysis of the androgen receptor gene is now commercially available. It detects upwards of 95% of the mutations for complete androgen insensitivity syndrome and partial androgen insensitivity syndrome. The analysis is performed on DNA obtained from buccal swabs. However, the testing is slow (about 6 weeks for results) and expensive (not covered by some insurance companies). […] A pelvic ultrasound examination is frequently useful. Identification of any mullerian structures, such as uterus or fallopian tubes, is inconsistent with a diagnosis of complete androgen insensitivity syndrome or partial androgen insensitivity syndrome. […] Histologic examination of the testes in patients with complete androgen insensitivity syndrome or partial androgen insensitivity syndrome should show fairly normal testicular structure, although the numbers of spermatogonia and/or sperm may be reduced markedly in postpubertal patients.

• #9 Androgen insensitivity syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Androgen_insensitivity_syndrome

  Androgen insensitivity syndrome (AIS) is a condition involving the inability to respond to androgens, typically due to androgen receptor dysfunction. […] The diagnosis of AIS requires thorough exclusion of other causes. […] Clinical findings indicative of AIS include the presence of a short vagina or undermasculinized genitalia, partial or complete regression of Müllerian structures, bilateral nondysplastic testes, and impaired spermatogenesis and/or virilization. […] Laboratory findings include a 46,XY karyotype and typical or elevated postpubertal testosterone, luteinizing hormone, and estradiol levels. […] The diagnosis of AIS is confirmed if androgen receptor gene sequencing reveals a mutation, although not all individuals with AIS (particularly PAIS) will have an AR mutation. […] Each of the three types of AIS (complete, partial, and mild) has a different list of differential diagnoses to consider.

• #10 Orphanet: Partial androgen insensitivity syndrome

  https://www.orpha.net/en/disease/detail/90797

  A difference of sex development (DSD) distinct from complete AIS (CAIS) characterized by the presence of abnormal genital development in a 46,XY individual with normal testis development and partial responsiveness to age-appropriate levels of androgens. […] The diagnosis is based on clinical and biochemical findings in XY patients with varying degrees of under-masculinization. The typical hormone profile is increased luteinizing hormone (LH) and testosterone levels, which is used as a screening test for MAIS with male factor infertility. Serum anti-Mullerian hormone (AMH) levels may be normal or increased. A pelvic ultrasound, MRI or cysto-urethroscopy confirm the presence of Wolffian duct structures and the absence of Mllerian structures. A utriculus or vaginal remnant is often visualized on urethroscopy. Positive mutation analysis of the AR gene and the mutant AR confirmed to be pathogenic in a reporter gene assay confirms the diagnosis.

• #10 Orphanet: Partial androgen insensitivity syndrome

  https://www.orpha.net/en/disease/detail/90797

  Human chorionic gonadotropin (hCG) stimulation should be performed to exclude an androgen biosynthetic defect. A urinary steroid profile is reliable to exclude 5-alpha-reductase deficiency after six months of age. Other differential diagnoses include 46,XY partial gonadal dysgenesis, congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency, Denys-Drash syndrome, Smith-Lemli-Opitz syndrome, and PAIS with a normal AR. The latter condition is strongly associated with low birth weight due to fetal growth restriction.

• #11 Androgen Insensitivity Syndrome – MD Searchlight

  https://mdsearchlight.com/sexual-health/androgen-insensitivity-syndrome/

  In simple terms, the diagnosis of conditions called CAIS (Complete Androgen Insensitivity Syndrome) and PAIS (Partial Androgen Insensitivity Syndrome) includes assessing physical symptoms, hormone levels, as well as ruling out problems with testosterone production. Genetic testing can also be used to confirm these conditions. […] To rule out issues with testosterone production, doctors may recommend measuring levels of testosterone, a hormone known as luteinizing hormone (LH), and follicle-stimulating hormone (FSH) within the first year of life. This evaluation will help identify any abnormalities in hormone production which might indicate these syndromes. […] Through these tests, doctors assess two key problems with hormone synthesis: 17-beta-hydroxysteroid dehydrogenase deficiency and 5-alpha-reductase deficiency. In people with CAIS and PAIS, testosterone responses after the hCG stimulation test are typically normal. Low testosterone production after this test may suggest a 17-beta-hydroxysteroid dehydrogenase deficiency.

• #12 Diagnostic Challenges in Androgen Insensitivity Syndrome & 5 Alpha Reductase Deficiency | BSPED2009 | 37th Meeting of the British Society for Paediatric Endocrinology and Diabetes | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0023/ea0023p25

  Diagnostic Challenges in Androgen Insensitivity Syndrome and 5 Alpha Reductase Deficiency. The clinical differentiation between androgen insensitivity syndrome (AIS) and 5 alpha reductase deficiency (5-ARD) can be difficult. Presenting features may be similar and initial investigations may still not be discriminatory. All ten children had a 46XY male karyotype. Four children were raised as male. Three out of the six females had an initial diagnosis of AIS, but subsequent re-evaluation revealed a diagnosis of 5-ARD. A urine steroid profile (USP) and then genetic analysis confirmed the diagnosis of 5-ARD. A child whose sibling had complete AIS also subsequently had a diagnosis of 5-ARD on urine steroid profile. A diagnosis of 5-ARD was subsequently made on urinary steroid profile and confirmed on genetic testing. This series revealed that clitoromegaly and inguinal lumps were a common finding in females with 5-ARD. Thus females with a diagnosis of AIS were re-evaluated and subsequently 3 of them were reclassified as 5-ARD. We reinforce the need to evaluate these children using a combination of USP, HCG test genetics.

• #13 Invitae Androgen Insensitivity Panel | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-04412

  The Invitae Androgen Insensitivity Panel analyzes AR and SRD5A2, two genes that are associated with ambiguous or feminized external sexual development in an individual with a 46,XY chromosome complement. Pathogenic changes in the AR gene cause androgen insensitivity; changes in SRD5A2 disrupt the conversion of testosterone into active dihydrotestosterone. […] Genetic testing of these genes may confirm a diagnosis and help guide treatment and gender-assignment decisions. Identification of a disease-causing variant can also guide genetic counseling and inform risk assessment for other relatives. […] Androgen insensitivity syndrome (AIS) due to defective function or absence of the androgen receptor is characterized by variable levels of virilization and infertility in all affected individuals and by female or ambiguous external genitalia in a 46,XY individual.

• #14 Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor gene | Scientific Reports

  https://www.nature.com/articles/srep32819

  Mutations in the X-linked androgen receptor (AR) gene underlie complete androgen insensitivity syndrome (CAIS), the most common cause of 46,XY sex reversal. […] Molecular genetic diagnosis of CAIS, however, remains uncertain in patients who show normal coding region of AR. […] Our results show that patients with CAIS and normal AR coding region need to be examined for deep intronic mutations that can lead to pseudoexon activation. […] The identification of a pathogenic mutation in AR confirms the diagnosis of AIS, especially in the milder forms which have some phenotypic overlap with other disorders of sex development. […] Here, we demonstrate a new mechanism for CAIS. […] We show that a deep intronic pseudoexon-activating mutation in the intron between exons 6 and 7 of AR, detected in two siblings with CAIS with normal AR coding region and conserved splice sites, leads to aberrant splicing of the AR mRNA and insufficient AR protein production. […] In conclusion, AR cDNA together with intronic sequences should be examined in CAIS patients with normal coding region and conserved splice sites of AR. […] The precise molecular genetic diagnosis is of crucial importance for genetic counseling of the patients and their family members.

• #15 SciELO Brazil – Androgen insensitivity syndrome: a review Androgen insensitivity syndrome: a review

  https://www.scielo.br/j/aem/a/98DLW9RbrG7knCMNdRcGdtM/

  Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. PAIS should be considered in all individuals with atypical genitalia at birth regardless of the degree of external genitalia virilization and MAIS is a possible diagnosis in males with persistent gynecomastia and or infertility. The AIS diagnosis is confirmed by the presence of allelic variants in the AR gene. Sequencing of the entire AR gene is recommended for all 46,XY DSD newborns, regardless of a familial history of DSD or AIS. In the absence of allelic variants in AR a multiplex ligation-dependent probe amplification (MLPA) can be helpful in order to detect deletions, insertions and duplications in the AR gene. Molecular diagnosis is achieved in almost all patients with CAIS and in a lower frequency in PAIS individuals. In AIS, gender identity usually follows the sex of rearing, but quality of sexual life, sexual functioning and quality of life can be slightly compromised and are important issues for keeping patients in psychological care.

• #16 Complete androgen insensitivity syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Complete_androgen_insensitivity_syndrome

  Complete androgen insensitivity syndrome (CAIS) is an AIS condition that results in the complete inability of the cell to respond to androgens. […] CAIS is usually not suspected until the menses fail to develop at puberty, or an inguinal hernia presents during premenarche. […] A diagnosis of CAIS or Swyer syndrome can be made in utero by comparing a karyotype obtained by amniocentesis with the external genitalia of the fetus during a prenatal ultrasound. […] The diagnosis of CAIS is confirmed when androgen receptor (AR) gene sequencing reveals a mutation, although up to 5% of individuals with CAIS do not have an AR mutation.

• #17 Pathogenesis and clinical features of disorders of androgen action – UpToDate

  https://www.uptodate.com/contents/pathogenesis-and-clinical-features-of-disorders-of-androgen-action

  Over 1000 mutations, as well as some larger structural alterations, have been identified in patients with all forms of androgen insensitivity syndrome, and these mutations can be spread out over the whole coding region. […] Furthermore, a distinct class of AR mutation-negative patients with AIS have been described, in whom the AR-responsive target gene apolipoprotein D (APOD) is diminished in genital skin fibroblasts. The exact molecular defect in these patients has not been identified yet.

• #18 Androgen insensitivity syndrome | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/androgen-insensitivity-syndrome?lang=us

  Androgen insensitivity syndrome (AIS), also known as testicular feminization syndrome, results from end-organ resistance to androgens, particularly testosterone. AIS may be complete or incomplete with variable imaging findings. […] Usually, the first modality to locate the testes, and document absent uterus. […] The modality of choice to accurately delineate Mllerian duct anomalies, and localize testes. It may also diagnose testicular malignancy, if any, in cryptorchid testes. […] These patients have an increased incidence of malignancy in the undescended testes: seminoma, gonadoblastoma. […] Role of imaging in the diagnosis and management of complete androgen insensitivity syndrome in adults.

• #19

  https://irispublishers.com/gjpnc/fulltext/diagnosis-and-management-of-androgen.ID.000584.php

  Androgen Insensitivity Syndrome (AIS) is a rare X-linked disorder characterised by an impaired virilisation in an individual with 46, XY karyotype. […] The diagnosis of AIS may be made before or after puberty using karyotyping, ultrasounds and MRI scans. […] The diagnosis of AIS should be established in someone that has a 46, XY karyotype with feminisation of the external genitalia, abnormal secondary characteristics and infertility. […] A molecular DNA analysis of those with AIS would most likely show a mutation in the various regions of the AR gene that causes frameshifts, deletions and single base mutations which can reduce the transcriptional activity of the Androgen receptor. […] The use of ultrasonography is the first line to look for Mullerian structures and an MRI can assist in locating the undescended testes in the abdominal cavity.

• #19

  https://irispublishers.com/gjpnc/fulltext/diagnosis-and-management-of-androgen.ID.000584.php

  A hCG test can also help to exclude a 5-alpha reductase 2 deficiency and a decreased testosterone biosynthesis that may present with similar clinical presentations. […] A diagnosis of AIS should be carried out with full disclosure that involves the patients and the family using an MDT that addresses functional, sexual and psychological issues. […] It is vital to establish a correct diagnosis of the type of AIS and address the main clinical presentations whilst forming a management plan.

• #20 Androgen Insensitivity Syndrome: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/924996-overview

  A karyotype is essential to differentiate an undermasculinized male from a masculinized female. […] Mutation analysis of the androgen receptor gene is now commercially available. It detects upwards of 95% of the mutations for complete androgen insensitivity syndrome and partial androgen insensitivity syndrome. […] The use of a magnetic resonance imaging before surgery appears to be helpful in localizing and planning for removal of the gonads for malignancy risk reduction and preventing injury to other structures. […] Timing of gonadectomy in patients with complete androgen insensitivity syndrome-current recommendations and future directions.

• #21 What Is Androgen Insensitivity Syndrome?

  https://www.icliniq.com/articles/genetic-disorders/androgen-insensitivity-syndrome

  How Androgen Insensitivity Syndrome Can Be Diagnosed? […] PAIS is frequently diagnosed right after birth by examining a baby’s genitals. However, CAIS or MAIS may not become apparent until the age of 11 or 12, when puberty begins. This is when a healthcare provider may notice problems. A child with CAIS may or may not have menstrual periods or pubic hair. A child with MAIS may retain a small penis or develop breast tissue. During puberty, undescended testicles can also herniation or bulge through a hole in the abdominal wall. If the child has surgery for an inguinal hernia, healthcare providers may discover undescended testicles. […] Since androgen insensitivity syndrome does not exclusively exhibit the phenotypes associated with androgen sensitivity, other potential causes must be thoroughly ruled out before diagnosing androgen insensitivity syndrome. […] Although not everyone with androgen insensitivity syndrome (especially partial androgen insensitivity syndrome) will have an androgen receptor mutation, the diagnosis of androgen insensitivity syndrome is confirmed if androgen receptor gene sequencing reveals a mutation.

• #22 Androgen insensitivity syndrome | Radiology Case | Radiopaedia.org

  https://radiopaedia.org/cases/androgen-insensitivity-syndrome-8?lang=us

  Primary amenorrhea. […] The MRI features are consistent with androgen insensitivity syndrome with female external genitalia (male pseudohermaphroditism). […] Androgen insensitivity syndrome (AIS), also known as testicular feminization syndrome, results from end-organ resistance to androgens, particularly testosterone. […] Affected individuals are genotypically male with a 46XY karyotype but with a female phenotype (male pseudohermaphroditism) and often have bilateral cryptorchidism. […] The main differential diagnosis is Mayer-Rokitansky-Kuster-Hauser syndrome which has a female karyotype with normal female genitalia, and ovaries, but the uterus is rudimentary or absent.

• #23

  https://step1.medbullets.com/evidence/20301602

  DIAGNOSIS/TESTING: The diagnosis of AIS is established in an individual with a 46,XY karyotype who has: undermasculinization of the external genitalia, impaired spermatogenesis with otherwise normal testes, absent or rudimentary mullerian structures, evidence of normal or increased synthesis of testosterone and its normal conversion to dihydrotestosterone, and normal or increased luteinizing hormone (LH) production by the pituitary gland; AND/OR a hemizygous pathogenic variant in AR identified by molecular genetic testing. […] For an apparently asymptomatic older or younger sib who has normal external female genitalia and who has not yet undergone menarche, a karyotype can be done first. For those phenotypic females who have a 46,XY karyotype, molecular genetic testing for the known AR variant in the family can be pursued next. If the AR variant in the family is not known, androgen binding assays could be considered.

• #24 Androgen Insensitivity Syndrome | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/17524

  Androgen insensitivity syndrome (AIS) is a common etiology of sexual developmental disorders resulting in varying phenotypes. […] Therefore, it is crucial for the clinician to have an understanding of the physiology of the androgen receptors mechanism to diagnose the condition as CAIS or PAIS accurately and plan the treatment course from birth to adulthood. […] The diagnosis of CAIS and PAIS includes assessing clinical and biochemical features, 46 XY karyotype, and exclusion of defects in testosterone synthesis. Furthermore, confirmation is possible with genetic testing. […] In addition to clinical features, biochemical testing may not be adequate to establish the diagnosis of CAIS or PAIS. Therefore, molecular genetic studies become imperative to diagnose CAIS or PAIS. […] The mutational analysis may confirm the diagnosis of androgen insensitivity syndrome. However, PAIS still poses a substantial amount of challenge for clinicians to predict a genotype-phenotype correlation and further clinical prognosis. […] The interprofessional approach is also beneficial in the education of healthcare professionals to interpret diagnostic tests accurately and avoid incorrect diagnoses and treatment of individuals from infancy to adulthood.

• #25

  https://111.wales.nhs.uk/encyclopaedia/a/article/androgeninsensitivitysyndrome

  If a surgeon thinks they’ve found testicles in a baby’s tummy during a hernia repair operation, a small tissue sample (biopsy) may be taken and analysed to confirm they are testicles and not ovaries. […] If someone in your family has AIS and the specific genetic fault causing it has been identified, it may be possible to have a blood test to check if you carry the same fault and are at risk of passing it on to any children you have. […] Testing can also be carried out in unborn babies when there’s a known family history of AIS. […] There are 2 main tests that can be carried out during pregnancy to determine whether a baby has the condition: chorionic villus sampling (CVS) and amniocentesis.

• #26 Androgen Insensitivity Syndrome | Embryo Project Encyclopedia

  https://embryo.asu.edu/pages/androgen-insensitivity-syndrome

  Blood levels of testosterone and DHT may be above normal due to the lack of the negative feedback loop between the anterior pituitary gland and the blood level of androgens, a feedback loop that normally keeps the level of androgens released by the testes in balance. […] Many physicians recommend removal of the testes prior to, or immediately following, the age of puberty due to an increased risk of testicular cancer. […] In infants born with MAIS, parents often raise the children as male, as those infants exhibit mild alteration of normal male genitalia. […] For some children born with AIS, treatments didn’t include anatomical surgeries other than the removal of the testes to prevent testicular cancer. […] Doctors can identify fetuses whose external genitalia does not match their genetic sex. To do so, doctors use ultrasound to view the fetus in the womb, and they use either sampling of the placental tissue (chorionic villi sampling) or sampling of amniotic fluid (amniocentesis) to obtain cells that will reveal the genetic sex of the fetus.

• #27 Is there a test to find out if I have androgen insensitivity syndrome? | Intersex Society of North America

  https://isna.org/faq/conditions/ais_test/

  Is there a test to find out if I have androgen insensitivity syndrome? The answer depends upon exactly what you are looking for diagnostic information, or carrier status. If you were born with female genitals and testes, and have very sparse or absent pubic hair, you most likely have complete AIS. Testing for partial AIS is more problematic than the complete form. Hormonal tests in a newborn with 46 XY karyotype and ambiguous genitals will show normal to elevated testosterone and LH, and a normal ratio of testosterone to DHT. A family history of ambiguous genitals in maternal relatives suggests partial androgen insensitivity. If you are wondering if you are a carrier, or if you know that you are a carrier and are wondering about the status of your fetus, genetic testing is possible. AIS has been diagnosed as early as 9-12 weeks gestation by chorionic villus sampling (sampling tissue from the fetal side of the placenta). By the 16th week it can be detected by ultrasound and amniocentesis. However, prenatal diagnosis is not indicated unless there is a family history of AIS. […] See the following for details of testing.

• #28 Complete Androgen Insensitivity Syndrome (CAIS) | Lurie Children’s

  https://www.luriechildrens.org/en/specialties-conditions/complete-androgen-insensitivity-syndrome/

  Complete Androgen Insensitivity Syndrome (CAIS) is a genetic condition characterized by the body’s inability to respond to testosterone, despite having 46,XY chromosomes and functional testes that produce this hormone. […] Diagnosis of CAIS can occur at various stages of life and for different reasons: Genetic testing during pregnancy or after birth may reveal 46,XY chromosomes despite typical female external genitalia. In adolescence, the absence of menstruation coupled with imaging studies (such as ultrasound) revealing the absence of a uterus and the presence of testicles in the groin, pelvis, or abdomen can lead to diagnosis. Elevated levels of testosterone in hormone tests or the identification of testicles during hernia surgery may also prompt diagnosis.

• #29 Orphanet: Complete androgen insensitivity syndrome

  https://www.orpha.net/en/disease/detail/99429

  Complete androgen insensitivity syndrome (CAIS) is a form of androgen insensitivity syndrome (AIS), a disorder of sex development (DSD), characterized by the presence of female external genitalia in a 46,XY individual with normal testis development but undescended testes and unresponsiveness to age-appropriate levels of androgens. […] The diagnosis is based on clinical and biochemical findings in a female with a 46,XY karyotype. The typical hormone profile is increased basal luteinizing hormone (LH) and testosterone levels in adults, and increased testosterone levels in infants following human chorionic gonadotropin (hCG) stimulation. Serum anti-Mllerian hormone (AMH) levels are normal or increased. Pelvic ultrasound or MRI reveal absent Mllerian structures (uterus, Fallopian tubes and upper vagina), due to the action of testicular anti-Mllerian hormone (AMH). Wolffian duct derivatives (vas deferens, epididymis, seminal vesicle) are absent due to androgen resistance. Mutation analysis of the AR gene confirms the diagnosis.

• #30 Complete Androgen Insensitivity Syndrome – ISS

  https://www.iss.it/en/-/complete-androgen-insensitivity-syndrome

  Androgen Insensitivity Syndrome (AIS) is the most common form of Variation of Sex Characteristics (VSC)/Difference of Sex Development (DSD) in individuals with XY chromosomes. […] Identification Suspicion of CAIS generally occurs in adolescence in people assigned female at birth because of their typically female external genitalia, when their first menstrual cycle (menarche) fails to occur. […] The genetic analysis of the karyotype and the identification of the androgen receptor (AR) gene mutations will confirm the suspicion and diagnosis of CAIS.

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

  https://www.mdpi.com/1648-9144/57/11/1142

  At the age of 20 years, the patient came to our observation with the diagnosis of CAIS. […] The patient was referred to our Division at the age of 20 years. […] We performed genetic testing to evaluate AR gene variants by Next-Generation Sequence (NGS) analysis. The results showed a novel missense variant of the AR gene that confirmed the clinical diagnosis of CAIS. […] The diagnosis and management of CAIS represent a difficult challenge for clinicians. […] A proper diagnosis is essential to enable appropriate management and genetic counseling of these patients and their families. […] The variation c.2242T>A p.(Phe748Ile) of the AR gene was found, and, to the best of our knowledge, this variant has never been described before. […] The patient presented with osteopenia at the lumbar spine (T-score = -2.3; BMD 0.950 g/centimeters²) despite her young age. […] This case report underlines the complexity of the management of CAIS and the urgent need to standardize the diagnostic and therapeutic strategies for these patients. […] Finally, AR gene analysis is mandatory to confirm a definitive diagnosis of CAIS.

• #32 Pediatric androgen insensitivity syndrome (AIS) – Children’s Health Dallas and Plano

  https://www.childrens.com/specialties-services/conditions/androgen-insensitivity-syndrome

  Complete androgen insensitivity is typically discovered at puberty, when a girl fails to start having periods or doesn’t develop pubic or underarm hair. […] Diagnosis starts with a thorough medical history and physical exam, including a pelvic exam. […] Additional testing may include: Blood test – to check hormone levels, Genetic testing (karyotype), Pelvic ultrasound or MRI of the pelvis to see the internal organs, confirming the absence of internal female reproductive organs. […] Partial androgen insensitivity is usually discovered when the baby is born because the external genitals aren’t clearly male or female (ambiguous genitalia).

• #33 Partial Androgen Insensitivity Syndrome – ISS

  https://www.iss.it/en/-/androgen-insensitivity-syndrome-ais-

  The condition is usually recognized clinically at birth by the presence of atypical male external genitalia and palpable testicles. […] PAIS diagnosis requires that the variant of the genus AR be identified; this, however, only happens in 40% of cases.

• #34 Partial Androgen Insensitivity Syndrome, Commentary 2 | Journal of Ethics | American Medical Association

  https://journalofethics.ama-assn.org/article/partial-androgen-insensitivity-syndrome-commentary-2/2005-11

  While delivering Mrs. Burdetts third child, her obstetrician observed that the baby had ambiguous external genitalia; on the evidence of the labioscrotal folds and incompletely formed penis or clitoris, the babys sex could not be determined on sight. […] Genetic tests performed the next day revealed that the baby had a 46,XY karyotype. Based on this and on the ratios of testosterone to luteinizing hormone and to dihydrotestosterone, the Burdett newborn was diagnosed with partial androgen insensitivity syndrome (PAIS). […] The first order of business in the management of this childs care should be to make a definitive diagnosis of the specific intersex disorder. Based on karyotype and endocrine studies, the child appears to have a partial androgen insensitivity syndrome. This diagnosis can be further confirmed by PCR analysis of venous blood for chromosomal abnormalities of the androgen receptor.

• #35 Partial Androgen Insensitivity Syndrome, Commentary 2 | Journal of Ethics | American Medical Association

  https://journalofethics.ama-assn.org/article/partial-androgen-insensitivity-syndrome-commentary-2/2005-11

  Findings from the physical examination and work-up need further clarification. The presence and position of gonads should be defined. The size and anatomy of the penis/clitoris and labioscrotal folds should also be determined to confirm the degree of virilization, and an abdominal ultrasound should be done to confirm absence of mullerian tissue. […] The management issues for this newborn include sex assignment and appropriate treatment of the gonads and external genitalia. Partial androgen insensitivity, unlike complete androgen insensitivity, is an intersex condition for which no general consensus exists as to the better sex assignment. […] Thus, more than 1 scenario is possible with this patient. One option may be to assign sex in the newborn period and carry out sex-appropriate surgical reconstruction.

• #36 Mild Androgen Insensitivity (MAIS): A challenging clinical and laboratory diagnosis | ECE2022 | European Congress of Endocrinology 2022 | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0081/ea0081ep928

  Mild Androgen Insensitivity (MAIS): A challenging clinical and laboratory diagnosis […] Mutations in the AR gene can disrupt its function leading to Androgen Insensitivity Syndrome (AIS). […] Due to its variable presentation, MAIS can prove challenging to diagnose clinically and biochemically. […] The case reported here is consistent with mild androgen insensitivity. […] Patients who present with gynaecomastia should always undergo adequate endocrine and genetic testing to reach a conclusive diagnosis.

• #37 Androgen insensitivity syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/androgen-insensitivity-syndrome/

  People with partial androgen insensitivity can have genitalia that look typical for females, genitalia that have both male and female characteristics, or genitalia that look typical for males. […] People with mild androgen insensitivity are born with male-typical sex characteristics, but they are often infertile and tend to experience breast enlargement at puberty. […] Variants (also called mutations) in the AR gene cause androgen insensitivity syndrome. […] This gene provides instructions for making a protein called an androgen receptor. […] Variants in the AR gene prevent androgen receptors from working properly, which makes them less able to bind to testosterone and regulate gene activity. […] This condition is inherited in an X-linked recessive pattern. […] About 70 percent of all cases of androgen insensitivity syndrome are inherited from people who carry an altered copy of the AR gene on one of their two X chromosomes.

• #38 Androgen Insensitivity: Symptoms, Causes, and Treatment

  https://www.verywellhealth.com/androgen-insensitivity-4173975

  Other tests may include biopsying the gonads. In all individuals with androgen insensitivity, they will have testes rather than ovaries. It is also possible to look for mutations in the androgen receptor genes. However, while this is a reasonably reliable marker for CAIS, it is not for PAIS. Only a fraction of mutations that cause PAIS has been identified to date.

• #39 Androgen Insensitivity Syndrome – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1429/

  Androgen insensitivity syndrome (AIS) should be suspected in an individual with the following clinical, family history, radiologic, and supportive laboratory findings. […] The diagnosis of AIS is explained to the affected individual and family in an empathic environment, with both professional and family support.

• #40 Complete Androgen Insensitivity Syndrome: A Rare Case with 47, XXY/46, XY Mosaic Karyotype and Literature Review

  https://clinmedjournals.org/articles/ogcr/obstetrics-and-gynaecology-cases-reviews-ogcr-9-227.php?jid=ogcr

  After the diagnosis of AIS is confirmed, the treatment needs to consider many factors, including genetic counseling, psychosocial gender, endocrine status, the possibility of orthopedic external genitalia and so on. […] The specific timing of orchiectomy is still inconclusive. At present, it is generally recommended that after the onset of puberty, orchiectomy can be performed once the height and breasts have matured. […] Long-term estrogen replacement therapy is required after surgery, which helps to induce puberty, maintain secondary sexual characteristics, promote the formation of bone mineral peaks and prevent bone loss, so as to benefit physical and socio-mental health. […] The current point of view is that vaginal molds or regular sex life can effectively expand the vagina and achieve the desired depth, which is a simple, safe and effective method.

• #40 Complete Androgen Insensitivity Syndrome: A Rare Case with 47, XXY/46, XY Mosaic Karyotype and Literature Review

  https://clinmedjournals.org/articles/ogcr/obstetrics-and-gynaecology-cases-reviews-ogcr-9-227.php?jid=ogcr

  Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disease caused by the absence or defects of androgen receptor (AR). […] The clinical manifestations of CAIS are relatively insidious. Clinicians should master the characteristics of this disease, identify carefully, make a clear diagnosis, and then develop an individualized treatment plan, so as to improve the life quality of patients and reduce the occurrence of tumors as much as possible. […] At present, the research on AIS has advanced to molecular and gene levels, but its clinical diagnosis still needs to be established on the combination with clinical manifestations, sex hormone determination, gonadal pathological examination and family genetic history. […] The following karyotype test will help to early diagnosis and treatment.

• #41 Androgen Insensitivity Syndrome Symptoms, Doctors, Treatments, Advances & More | MediFind

  https://www.medifind.com/conditions/androgen-insensitivity-syndrome/257

  Treatment and gender assignment can be a very complex issue and must be targeted to each individual person. Treatment guidelines are still evolving. […] It is vital that children with AIS and their parents receive care and support from a health care team that includes different specialists with expertise in gender medicine. This should include mental health professionals to help provide support for both children and their parents.

• #42 Androgen Insensitivity Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK542206/

  Androgen insensitivity syndrome (AIS) is a common etiology of sexual developmental disorders and results in varying phenotypes. […] This activity reviews the evaluation and treatment of androgen insensitivity syndrome (AIS) and highlights the role of the interprofessional team in evaluating and treating patients with this condition. […] Describe the appropriate evaluation of androgen insensitivity syndrome. […] The diagnosis of CAIS and PAIS includes assessing clinical and biochemical features, 46 XY karyotype, and exclusion of defects in testosterone synthesis. Furthermore, confirmation is possible with genetic testing. […] In addition to clinical features, biochemical testing may not be adequate to establish the diagnosis of CAIS or PAIS. Therefore, molecular genetic studies become imperative to diagnose CAIS or PAIS. […] The interprofessional approach is also beneficial in the education of healthcare professionals to interpret diagnostic tests accurately and avoid incorrect diagnoses and treatment of individuals from infancy to adulthood.

• #43 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20230327/Discovery-enables-a-clear-diagnosis-for-more-patients-with-androgen-insensitivity-syndrome.aspx

  The discovery also provides a basis for further research on the development of sexual characteristics and enables a clear diagnosis for more patients with AIS: „Previously, patients with androgen insensitivity but without a modification in the androgen receptor did not receive a clear diagnosis despite having clear symptoms,” says Hornig. „Now we can make a clear diagnosis for those in whom DAAM2 is altered.”

• #44 Challenges in clinical and laboratory diagnosis of androgen insensitivity syndrome: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-446

  Androgen is a generic term usually applied to describe a group of sex steroid hormones. […] Physical examination, karyotype testing and molecular analysis of the androgen receptor were critical in making the correct diagnosis of complete androgen insensitivity syndrome. […] 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. […] The aim of the investigation reported here was to provide a genetic diagnosis of a teenage girl with normal male karyotype using fluorescence in situ hybridization (FISH) and PCR in order to determine the nature and the extent of the mutation that affected the AR gene.

• #45 Challenges in clinical and laboratory diagnosis of androgen insensitivity syndrome: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-446

  The results reported in this paper underline the fact that great care must be taken when selecting genetic testing tools to be utilized to reach the proper diagnosis for AIS. […] However, due to complex chromosome aberrations or other genomic mutations, other molecular tools to detect and define DNA mutations, such as DNA sequencing, may be required to properly reach the conclusion of a diagnosis of AIS.

• #46

  https://www.ijrcog.org/index.php/ijrcog/article/view/15180

  Partial androgen insensitivity syndrome (PAIS) is a rare 46XY disorder that results from mutations in androgen receptors leading to failure of normal masculinization of external genitalia in genetically male individuals. […] Early identification and multi-disciplinary management aiming at appropriate gender assignment, gonadectomy, reconstructive surgery, hormone replacement therapy and screening of other family members should be done.

• #47 A Very Early Diagnosis of Complete Androgen Insensitivity Syndrome Due to a Novel Variant in the AR Gene: A Neonatal Case Study

  https://www.mdpi.com/2227-9059/12/8/1742

  By analyzing the above clinical data, the preliminary diagnosis of CAIS was confirmed. […] Therefore, the molecular analysis of the AR gene was then performed resulting in a mutation in exon 4 of the AR gene. […] This is the first report of a novel mutation in exon 4 of the AR gene. […] The discovery of a new variant in the AR gene is crucial for several reasons, especially in the context of androgen insensitivity syndrome (AIS): (1) improved diagnosis: the identification of novel variants in the AR gene helps to confirm the diagnosis of AIS. […] Besides describing a new variant in the AR gene, we hereby emphasize the importance of a multidisciplinary approach that allows a very early diagnosis of AIS.

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