Materiały źródłowe

• #1 Atypical genitalia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/atypical-genitalia/symptoms-causes/syc-20369273

  Atypical genitalia, formerly called ambiguous genitalia, is a rare condition in which an infant’s genitals don’t appear to be clearly male or female on the outside. […] Your medical team looks for the cause of atypical genitalia and provides information and counseling that can help guide decisions about your baby’s sex and any needed treatment. […] Atypical genitalia usually happen when hormone changes during pregnancy stop or disturb an unborn baby’s developing sex organs. […] A change in the steps that influence fetal sex development can result in a mismatch between the appearance of a baby’s external genitals and the baby’s internal sex organs or genetic sex, typically XX or XY. […] Sometimes it’s not possible to find the cause of atypical genitalia. […] Diagnosis treatment.

• #2 Ambiguous Genitalia: Definition & Causes

  https://my.clevelandclinic.org/health/diseases/22470-atypical-genitalia-formerly-known-as-ambiguous-genitalia

  Atypical genitalia, formerly known as ambiguous genitalia, is a rare condition where your newborns external genitals dont look typically male or typically female. […] Atypical genitalia is a difference of sexual development (DSD). […] Most babies receive a diagnosis of ambiguous genitalia at birth. When its unclear if your newborn is male or female, your babys healthcare provider will order further tests to determine a diagnosis. […] Your babys healthcare provider will ask about your familys medical history and examine your babys external genitals. They may order several tests to determine the correct diagnosis. […] The first step of management is to identify the cause of atypical genitalia. Then, your babys healthcare provider will put together a treatment plan and sex assignment based on hormone tests and other test results.

• #2 Ambiguous Genitalia: Definition & Causes

  https://my.clevelandclinic.org/health/diseases/22470-atypical-genitalia-formerly-known-as-ambiguous-genitalia

  Ambiguous genitalia (atypical genitalia) can have profound physical, social and psychological effects on your child. Your childs genitals can shape the way they understand themselves. […] A diagnosis of ambiguous genitalia (atypical genitalia) in your newborn can be very distressing for you and your family.

• #3 Evaluation of the infant with atypical genital appearance (difference of sex development) – UpToDate

  https://www.uptodate.com/contents/evaluation-of-the-infant-with-atypical-genital-appearance-difference-of-sex-development

  Evaluation of the infant with atypical genital appearance (difference of sex development) […] Infants born with genitals that do not appear typically male or female, or that have an appearance discordant with the chromosomal sex (picture 1), are classified as having a difference (or disorder) of sex development (DSD; terminology discussed further below). DSDs with a genital appearance that is sufficiently atypical to prompt evaluation occur in approximately 1 in 1000 to 4500 live births. […] The evaluation of the infant with a DSD is presented here. Specific causes of DSDs and the management of affected infants are discussed separately. […] Many of these individuals present as newborns with an atypical genital appearance sometimes termed „ambiguous genitalia.”

• #4 Atypical genitalia – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/atypical-genitalia/diagnosis-treatment/drc-20369278

  Atypical genitalia is usually diagnosed at birth or shortly after. […] Sometimes, healthcare professionals may suspect atypical genitalia during pregnancy when results of blood tests of the unborn baby’s sex differ from the ultrasound imaging of the baby’s genitalia. […] But generally, the diagnosis is not made until after birth. Healthcare professionals who help with delivery may notice the signs of atypical genitalia in your newborn. […] If your baby is born with atypical genitalia, your doctor and other healthcare professionals work to find the cause. […] Your healthcare professional begins by asking questions about your family and medical history. […] Your baby has a physical exam to check for testicles and evaluate the genitalia. […] Using the information gathered from these tests, your healthcare professional may suggest a sex for your baby.

• #4 Atypical genitalia – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/atypical-genitalia/diagnosis-treatment/drc-20369278

  The suggestion is based on the cause, genetic sex, anatomy, future reproductive and sexual potential, probable adult gender identity, and discussion with you. […] Sometimes, a family may make a decision within a few days after the birth. […] But it’s important that families wait until tests are finished. […] The timing of surgery depends on your child’s specific situation. […] Some healthcare professionals prefer to postpone surgery done only for appearance. […] They suggest waiting until the person with atypical genitalia is mature enough to be part of the decision about sex assignment. […] For children with atypical genitalia, the sex organs may work properly in spite of how the genitals look on the outside. […] Children with atypical genitalia need ongoing medical care. […] This includes watching for complications, such as getting cancer screenings into adulthood.

• #5 Atypical genitalia

  https://johnsonmemorial.org/jmh-health/disease-conditions/con-20369257

  Atypical genitalia is usually diagnosed at birth or shortly after. […] Sometimes, healthcare professionals may suspect atypical genitalia during pregnancy when results of blood tests of the unborn baby’s sex differ from the ultrasound imaging of the baby’s genitalia. […] Healthcare professionals who help with delivery may notice the signs of atypical genitalia in your newborn. […] If your baby is born with atypical genitalia, your doctor and other healthcare professionals work to find the cause. […] The cause helps guide treatment and decisions about your baby’s sex. […] Your baby has a physical exam to check for testicles and evaluate the genitalia. […] Your baby will likely have these tests: Blood tests to measure hormone levels. […] Blood tests to look at chromosomes. This can show the genetic sex: typically, XX or XY.

• #5 Atypical genitalia

  https://johnsonmemorial.org/jmh-health/disease-conditions/con-20369257

  These blood tests also can show conditions caused by a gene change that affects sex organ development. […] Ultrasound of the pelvis and belly to look for testicles that haven’t descended, a uterus or a vagina. […] X-ray studies using a contrast dye to help give a clear picture of pelvic and belly structures. […] Sometimes minimally invasive surgery is needed to collect a tissue sample of your newborn’s reproductive organs. […] Using the information gathered from these tests, your healthcare professional may suggest a sex for your baby. […] The suggestion is based on the cause, genetic sex, anatomy, future reproductive and sexual potential, probable adult gender identity, and discussion with you. […] Sometimes, a family may make a decision within a few days after the birth. […] But it’s important that families wait until tests are finished. […] Sex assignment can be complex and delayed. […] Parents should be aware that as the child grows up, the child may make a different decision about gender identification.

• #6 Atypical genitalia | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/atypical-genitalia?content_id=CON-20369257

  Atypical genitalia is usually diagnosed at birth or shortly after. […] Sometimes, healthcare professionals may suspect atypical genitalia during pregnancy when results of blood tests of the unborn baby’s sex differ from the ultrasound imaging of the baby’s genitalia. […] Healthcare professionals who help with delivery may notice the signs of atypical genitalia in your newborn. […] If your baby is born with atypical genitalia, your doctor and other healthcare professionals work to find the cause. […] The cause helps guide treatment and decisions about your baby’s sex. […] Your healthcare professional begins by asking questions about your family and medical history. […] Your baby has a physical exam to check for testicles and evaluate the genitalia. […] Your baby will likely have these tests: Blood tests to measure hormone levels.

• #6 Atypical genitalia | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/atypical-genitalia?content_id=CON-20369257

  Blood tests to look at chromosomes. This can show the genetic sex: typically, XX or XY. […] These blood tests also can show conditions caused by a gene change that affects sex organ development. […] Ultrasound of the pelvis and belly to look for testicles that haven’t descended, a uterus or a vagina. […] X-ray studies using a contrast dye to help give a clear picture of pelvic and belly structures. […] Sometimes minimally invasive surgery is needed to collect a tissue sample of your newborn’s reproductive organs. […] Using the information gathered from these tests, your healthcare professional may suggest a sex for your baby. […] The suggestion is based on the cause, genetic sex, anatomy, future reproductive and sexual potential, probable adult gender identity, and discussion with you.

• #6 Atypical genitalia | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/atypical-genitalia?content_id=CON-20369257

  Sometimes, a family may make a decision within a few days after the birth. […] But it’s important that families wait until tests are finished. […] Sex assignment can be complex and delayed. […] Parents should be aware that as the child grows up, the child may make a different decision about gender identification.

• #7

  https://journals.lww.com/jiap/fulltext/2019/24030/a_clinical_approach_to_diagnosis_of_ambiguous.3.aspx

  Criteria for suspecting DSD include: (1) Overt genital ambiguity (e.g. cloacal exstrophy); (2) Apparent female genitalia with an enlarged clitoris and posterior labial fusion (e.g., CAH); (3) Apparent male genitalia with bilateral undescended testes, hypospadias, or micropenis; and (4) Discordance between genital appearance and a prenatal karyotype. […] The diagnosis is confirmed after karyotyping (46, XX) and hormonal assay. […] The diagnosis of AIS is confirmed by karyotyping suggestive of 46, XY (X linked recessive/autosomal recessive) DSD and increased LH, testosterone, oestradiol and sometimes increased follicle-stimulating hormone (FSH). […] Confirmation of each of them would require a detailed work-up including chromosomal evaluation, radiological investigations, hormonal evaluation, genitoscopy, laparoscopy/laparotomy, and gonadal biopsy for diagnostic and therapeutic purposes.

• #8 A Clinical Approach to Diagnosis of Ambiguous Genitalia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6568146/

  However, the important markers in clinical examination are often overlooked due to lack of knowledge and experience of most physicians dealing with pediatric DSD cases. […] This article aims to unfold the clinical clues to diagnose different types of DSDs gathered over 38 years of experience of the senior author in managing more than 1200 patients of DSD at a tertiary level institute. […] Criteria for suspecting DSD include: (1) Overt genital ambiguity (e.g. cloacal exstrophy); (2) Apparent female genitalia with an enlarged clitoris and posterior labial fusion (e.g., CAH); (3) Apparent male genitalia with bilateral undescended testes, hypospadias, or micropenis; and (4) Discordance between genital appearance and a prenatal karyotype. […] The diagnosis is confirmed after karyotyping (46, XX) and hormonal assay.

• #8 A Clinical Approach to Diagnosis of Ambiguous Genitalia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6568146/

  The diagnosis of AIS is confirmed by karyotyping suggestive of 46, XY (X linked recessive/autosomal recessive) DSD and increased LH, testosterone, oestradiol and sometimes increased follicle-stimulating hormone (FSH). […] Confirmation of each of them would require a detailed work-up including chromosomal evaluation, radiological investigations, hormonal evaluation, genitoscopy, laparoscopy/laparotomy, and gonadal biopsy for diagnostic and therapeutic purposes.

• #8 A Clinical Approach to Diagnosis of Ambiguous Genitalia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6568146/

  Disorders of sex development (DSD) are a sensitive and stressful condition for the family as well as the treating physician to deal with. […] The main issue in managing such cases is sex assignment. […] In this article, the authors try to identify the important clinical features in children presenting with various types of DSD, which may aid in making a quick provisional clinical diagnosis and expediting the diagnostic work-up. […] A complete evaluation of DSD case entails clinical presentation including the status of gonads, chromosomal analysis, hormonal evaluation, radiology (genitogram, ultrasound [USG], magnetic resonance imaging [MRI]) to look for Mullerian structures, endoscopy, and laparoscopy/laparotomy. […] The starting point of all these algorithms has been defined by the karyotype or the gonadal histology.

• #9 Ambiguous Genitalia (Disorders of Sexual Development) | 5-Minute Pediatric Consult

  https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617552/all/Ambiguous_Genitalia__Disorders_of_Sexual_Development_?q=Vaginitis

  Genital ambiguity occurs when it is not possible to categorize the gender of the child based on outward genital appearance. […] Can result from various disorders of sexual development (DSD), a generic term defined as a congenital condition in which development of chromosomal, gonadal, or phenotypic sex is atypical. […] Criteria that suggest that a child may have a DSD include the following: Bilateral nonpalpable testes, Micropenis (stretched length 2.5 cm at full term), Severe hypospadias or mild hypospadias with a unilateral undescended testis, Clitoromegaly (width 6 mm or length 9 mm), posterior labial fusion, An inguinal/labial mass, Family history of a DSD, Discordance between genital appearance and prenatal karyotype. […] Disorders causing genital ambiguity are congenital and usually present in the newborn period.

• #9 Ambiguous Genitalia (Disorders of Sexual Development) | 5-Minute Pediatric Consult

  https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617552/all/Ambiguous_Genitalia__Disorders_of_Sexual_Development_?q=Vaginitis

  Partial androgen insensitivity syndrome (PAIS) is the next most common cause of DSD (classified as a 46,XY DSD). […] 46,XY DSD may be associated with mutations in the following genes: Genes involved in testicular development: sex-determining region on Y (SRY), SOX9, steroidogenic factor 1 (SF-1), Wilms tumor suppressor (WT1) gene, WNT4 duplication, and DAX1 duplication. […] 46,XX DSD may be associated with mutations in the following genes: Genes involved in ovarian development and leading to gonadal dysgenesis: FSH receptor (FSHR), SF-1. […] Incomplete masculinization of the male fetus can be caused by disorders of T synthesis (e.g., CAH, 5-reductase deficiency), unresponsiveness to T action (androgen insensitivity syndromes), or defects in testicular development (complete or partial gonadal dysgenesis). […] Masculinization of the female fetus is caused by exposure to androgens, either endogenous or exogenous. The most common cause is CAH in which the fetal adrenal glands overproduce androgens in an attempt to produce cortisol.

• #10 Atypical genitalia in neonates – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/868

  Atypical genitalia (i.e., a genital phenotype that is neither clearly male nor female) are caused by the atypical development of chromosomal, gonadal, or anatomical sex. The complex group of disorders that cause atypical genitalia are called differences of sex development (DSD). […] 46,XY DSD can be due to several etiologies and usually requires a more extensive diagnostic evaluation. […] The initial management of a neonate with atypical genitalia is a social and clinical emergency. The local team has a key role in coordinating the initial assessment and investigations, and supporting parents. It is important there is early discussion with a more specialist multidisciplinary team with expertise in pediatric endocrinology, genetics, and surgery, and with appropriate psychiatric/psychological support.

• #10 Atypical genitalia in neonates – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/868

  DSD most commonly present in the newborn period and can be classified as sex chromosome DSD, 46,XY DSD, or 46,XX DSD. A subset of children with DSD present at birth with atypical genitalia and without other dysmorphic features. […] This topic addresses the initial approach to neonates with atypical genitalia who are not identified as having a specific chromosomal syndrome in which atypical genitalia may be one of a number of presenting features. […] Key diagnostic factors include atypical genitalia with no palpable gonads, atypical genitalia with one palpable gonad, and atypical genitalia with bilaterally palpable gonads. […] 1st tests to order include chromosome analysis (karyotype), serum electrolytes and glucose, and pelvic ultrasound.

• #11 Atypical genitalia in neonates – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/868?locale=th

  Atypical genitalia (i.e., a genital phenotype that is neither clearly male nor female) are caused by the atypical development of chromosomal, gonadal, or anatomical sex. The complex group of disorders that cause atypical genitalia are called differences of sex development (DSD). […] 46,XY DSD can be due to several etiologies and usually requires a more extensive diagnostic evaluation. […] The initial management of a neonate with atypical genitalia is a social and clinical emergency. The local team has a key role in coordinating the initial assessment and investigations, and supporting parents. It is important there is early discussion with a more specialist multidisciplinary team with expertise in pediatric endocrinology, genetics, and surgery, and with appropriate psychiatric/psychological support.

• #11 Atypical genitalia in neonates – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/868?locale=th

  This topic addresses the initial approach to neonates with atypical genitalia who are not identified as having a specific chromosomal syndrome in which atypical genitalia may be one of a number of presenting features. […] Key diagnostic factors include atypical genitalia with no palpable gonads, atypical genitalia with one palpable gonad, and atypical genitalia with bilaterally palpable gonads. […] 1st tests to order include chromosome analysis (karyotype), serum electrolytes and glucose, and pelvic ultrasound. […] Tests to consider include serum 17 hydroxyprogesterone, plasma renin activity, and serum testosterone.

• #12 Disorders/differences of sex development (DSDs) for primary care: the approach to the infant with ambiguous genitalia – Indyk – Translational Pediatrics

  https://tp.amegroups.org/article/view/16975/html

  Unfortunately, a great number of cases do not have an identifiable cause, particularly among 46XY DSD, which highlights the importance of an experienced team with multidisciplinary focus. […] A thoughtful history and exam, along with an initial workup can be extremely helpful in progressing toward a working diagnosis. […] Without a diagnosis, it becomes difficult for the medical team to assist the family with proper guidance in assigning a sex of rearing and planning for the future. […] Key points in the history and exam are outlined in Table 3. […] The first conversations with the family need to set a positive tone where the new parents will be respectfully included and guided through the process. […] Assigning a sex of rearing is a great responsibility and obligation and should not be rushed.

• #12 Disorders/differences of sex development (DSDs) for primary care: the approach to the infant with ambiguous genitalia – Indyk – Translational Pediatrics

  https://tp.amegroups.org/article/view/16975/html

  The initial management of the neonate with ambiguous genitalia can be a very stressful and anxious time for families, as well as for the general practitioner or neonatologist. […] A timely approach must be sensitive and attend to the psychosocial needs of the family. […] In addition, it must also effectively address the diagnostic dilemma that is frequently seen in the care of patients with disorders of sex development (DSDs). […] Achieving optimal outcomes requires open and transparent dialogue with the family and caregivers, and should harness the resources of a multidisciplinary team. […] The causes of genital ambiguity in newborn period are listed in Table 1. […] The most common cause of ambiguous genitalia is congenital adrenal hyperplasia. […] CAH should be the primary consideration in any virilized infant with non-palpable gonads.

• #12 Disorders/differences of sex development (DSDs) for primary care: the approach to the infant with ambiguous genitalia – Indyk – Translational Pediatrics

  https://tp.amegroups.org/article/view/16975/html

  Parents must be involved and made to feel included in decision-making. […] Though the history of surgery in DSD is filled with controversy and regret, surgical intervention has an important role in certain circumstances. […] The major indications for surgery in DSD are gonadectomy and genital reconstructive surgery, and both carry significant controversy. […] There is increased risk of neoplasm in dysgenetic gonads carrying Y chromosome material, and in sex chromosome DSDs such as mixed/partial gonadal dysgenesis. […] Achieving a balance between adequate and excessive steroid dosing in CAH can be a challenge. […] Optimal care in CAH, as with other DSDs, requires a multidisciplinary team, including urologists, geneticists, social workers, psychologists. […] While clinical and molecular biology research have propelled us in breaking down the complexities of male and female sex development, it has been significantly shaped by decades of practical medical experience and the lessons learned from painful personal, family, and individual experiences.

• #13 Management of ambiguous genitalia – O&G Magazine

  https://www.ogmagazine.org.au/19/3-19/management-ambiguous-genitalia/

  The identification of ambiguous genitalia at birth is often the cause for significant distress and concern. […] Ambiguous genitalia can be the earliest feature of a Disorder of Sex Development (DSD), which covers a wide range of conditions where the chromosomal, gonadal or genital development is atypical. […] Although the commonest cause for ambiguous genitalia is congenital adrenal hyperplasia (CAH) in 46XX individuals, the diagnosis and management of patients with ambiguous genitalia can nevertheless be challenging and will require a multidisciplinary approach. […] We have designed this to be a simple guide to the approach, diagnosis and early management of neonates with ambiguous genitalia. […] Detailed family and prenatal history, followed by thorough physical examination for associated dysmorphic features, pigmentation, palpable gonad(s) and external genitalia appearance (including symmetry of the genitals, the site of the urethral opening, the presence of a hymen and vaginal opening or the presence of a urogenital opening) is required.

• #14 Disorders of sex development – Wikipedia

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

  Disorders of sex development (DSDs), also known as differences in sex development, variations in sex characteristics, sexual anomalies, or sexual abnormalities, are congenital conditions affecting the reproductive system, in which development of chromosomal, gonadal, or anatomical sex is atypical. […] Infants born with atypical genitalia often cause confusion and distress for the family. […] These professionals are capable of providing first line (prenatal) and second line diagnostic (postnatal) tests to examine and diagnose sexual anomalies. […] DSDs are defined as „any problem noted at birth where the genitalia are atypical in relation to the chromosomes or gonads”. […] The presence of gonads, uterus and vagina should be monitored. This can be done through abdominal ultrasounds. However, the absence of these sex organs will lead to difficulties in gender identification.

• #15 Atypical genitalia | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20369257/

  Atypical genitalia, formerly called ambiguous genitalia, is a rare condition in which an infants genitals dont appear to be clearly male or female on the outside. […] Atypical genitalia is not a disease; its a difference of sex development. Usually, atypical genitalia can be seen at or shortly after birth. […] Atypical genitalia is usually diagnosed at birth or shortly after. […] If your baby is born with atypical genitalia, your doctor and other healthcare professionals work to find the cause. The cause helps guide treatment and decisions about your babys sex. […] Using the information gathered from these tests, your healthcare professional may suggest a sex for your baby. […] The goal of treatment is long-term mental health and social well-being, as well as having as much sexual function and fertility as possible. […] In children with atypical genitalia, surgery may be used to keep healthy sexual function and create genitals that appear more typical. […] Children with atypical genitalia need ongoing medical care. This includes watching for complications, such as getting cancer screenings into adulthood.

• #16 Ambiguous genitalia Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/symptoms/ambiguous-genitalia

  Ambiguous genitalia is a rare condition where a child is born with outer genitals that do not clearly look either male or female. […] This condition is also called uncertain genitalia or atypical genitalia. […] Ambiguous genitalia is common in children with differences of sex development (DSD). […] Ambiguous genitalia may be discovered during the first well-baby exam. […] The provider will perform a physical exam which may reveal genitals that are not „typical male” or „typical female,” but somewhere in between. […] The following tests may be done: Chromosome analysis (karyotyping) to determine the person’s genetic makeup, Blood tests to check levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), Electrolyte tests, Specific molecular testing. […] Depending on the cause, surgery, hormone replacement, or other treatments are used to treat conditions that can cause ambiguous genitalia. […] There have been significant changes in treating ambiguous genitalia. […] Many experts now urge delaying definitive surgery for as long as is healthy, and ideally involving the child in the decision, unless surgery is needed for the health of the infant.

• #17 Differences (Disorders) of Sex Development (DSDs): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1015520-overview

  Infants born with ambiguous or abnormal genitalia may have indeterminate phenotypic sex […] Karyotype to rule out DSDs should be considered in a male-looking patient with bilateral undescended testes or unilateral undescended testis and hypospadias, whether the genitalia appear ambiguous or not […] Prompt diagnosis of the underlying cause of DSD is essential; 75% of those with 21-hydroxylase deficiency have salt-wasting nephropathy […] The diagnosis is confirmed by noting an elevated amniotic fluid level of 17-hydroxyprogesterone (17-OHP) during the second trimester or by HLA typing of the amniotic cells […] Following birth, CAH is diagnosed more often during the evaluation of a 46,XX child with ambiguous genitalia and nonpalpable gonads […] Diagnosis of this deficiency can be confirmed in a patient with a 46,XY karyotype by the presence of a high ratio of serum testosterone to DHT

• #17 Differences (Disorders) of Sex Development (DSDs): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1015520-overview

  Gender assignment in these patients has been the subject of considerable debate because of the major virilization that occurs at puberty […] The surgical results of a masculinizing operation in a mildly virilized infant are poor, and the burden of growing up with inadequate genitalia hardly seems justified […] Gonadal findings may include any combination of ovary, testis, or ovotestis […] The most common presentation is a phenotypic male with an inguinal hernia on one side and an impalpable contralateral gonad […] Appropriate surgical management is straightforward and includes orchiopexy for undescended testes […] The risk of gonadal malignancy is increased when a Y chromosome is present in the karyotype […] Gender assignment for patients with DMP and MGD remains under debate […] Prophylactic gonadectomy is advised in the Y mosaic Turner syndrome because the risk of gonadoblastoma is estimated to be 12% […] Gonadectomy becomes important as soon as the diagnosis is recognized followed by cyclic hormone replacement with estrogen and progestins.

• #18 15 DIAGNOSIS OF AMBIGUOUS GENITALIA AT PREPUBERIAL AGE BY THE THE CHRONIC hCG TEST | Pediatric Research

  https://www.nature.com/articles/pr1992200

  We evaluated the contribution of the chronic hCG test (50-100 U/kg/dose, 4/4 days, 4 doses) to the differential diagnosis of ambiguous genitalia in prepubertal age. […] We conclude that the testicular response to hCG at prepubertal age can be normal in true hermaphroditism and mixed gonadal dysgenesis, and that this test was useful for the identification of the testosterone synthesis errors and deficiency of 5-alpha-reductase.

• #19 Differences (Disorders) of Sex Development (DSDs) Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1015520-workup

  Routine workup in infants born with ambiguous genitalia should include genetic testing and endocrine screening. […] The diagnosis is evident if a difference (disorder) of sex development (DSD) is caused by chromosomal abnormalities. […] Hormonal diagnostics and serum electrolytes/chemistry levels are essential right after birth. […] In the absence of palpable testes, markedly elevated luteinizing hormone (LH) levels or lack of testosterone elevation in response to human chorionic gonadotropin (hCG) stimulation can indicate the absence of normally functioning testicular tissue in patients with nonpalpable gonads. […] A complete ultrasonographic (US) examination of the pelvic structures, as well as the perineal region and of the entire urinary tract, is recommended. […] Ambiguous genitalia, enlarged adrenal glands, and the presence of mllerian structures in a newborn are virtually pathognomonic for CAH.

• #19 Differences (Disorders) of Sex Development (DSDs) Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1015520-workup

  Cystourethroscopy before or during the definitive reconstructive surgical procedure may help better define the anatomy of the urogenital sinus and determine the exact location of the confluence where the vagina meets the urethra (ie, high, intermediate, or low). […] Laparoscopy allows the identification and biopsy of intra-abdominal gonads. […] Histologic analysis of gonadal biopsy specimens may identify ovarian tissue, testicular tissue, ovotestes, or streak gonads.

• #20

  https://link.springer.com/article/10.1007/BF02926947

  The pediatric radiologist plays a significant role in the evaluation and the treatment of infants with ambiguous genitalia. On the first day of life, an investigation should be initiated that includes studies, in particular a sonogram, to demonstrate the presence or absence of a uterus, and a genitogram to define the presence of a vagina. Once gender assignment has been made, information regarding the size of the vagina and its position in regard to the urogenital sinus becomes essential to the pediatric urologist when planning a course for reconstruction. […] The role of the radiologist in each of these states is discussed.

• #21

  https://scite.ai/reports/a-clinical-approach-to-diagnosis-RVpR6d9

  Disorder of sex development (DSD) merupakan kondisi anatomi organ seks atipikal sehingga organ kelamin tidak bisa diidentifikasi dengan jelas. […] Setiap kasus DSD perlu dilakukan pemeriksaan diagnostik secara menyeluruh untuk menentukan jenis dan penyebab, serta penatalaksanaan komprehensif sesuai dengan etiologi. […] Analisis kromosom merupakan pemeriksaan awal yang harus dilakukan pada DSD dan sebaiknya menggunakan teknik karyotyping untuk menilai kelainan struktur kromosom secara lebih baik. […] Pemeriksaan penunjang yang perlu dilakukan mencakup analisis kromosom, pemeriksaan kadar hormon steroid seks, serta pencitraan, seperti USG pelvis dalam 24 jam setelah kelahiran, genitogram, hingga MRI untuk menilai struktur Mullerian. […] Cytogenetic and molecular genetic studies play an essential role in diagnosis and decision-making and should be made affordable in developing countries for better patient care. […] In these cases, an integrated approach with detailed history and clinical examination supplemented by imaging, hormonal assays, karyotyping, and gonadal biopsy is necessary to arrive at a conclusive diagnosis.

• #22 Presentation: Neonate with ambiguous genitalia — In the Clinic

  https://www.genomicseducation.hee.nhs.uk/genotes/in-the-clinic/presentation-neonate-with-ambiguous-genitalia/

  In many babies who present with ambiguous genitalia in the newborn period, there will be a genetic cause. Genetic sex needs to be established rapidly for management purposes. […] All newborn babies presenting with ambiguous genitalia need genomic testing to establish genetic sex and possible genetic cause, in parallel with biochemical investigations. […] There are two types of genomic testing that are required in this scenario: a rapid common aneuploidy test or karyotype (chromosome test) to establish the genetic sex; and additional genomic testing to determine the cause of the ambiguous genitalia. […] To establish the genetic sex, the appropriate test is: R314 Ambiguous genitalia presenting neonatally (including common aneuploidy testing and, if necessary, karyotype). […] If this test does not identify aneuploidy and biochemical investigations suggest that congenital adrenal hyperplasia (CAH) is the likely diagnosis then proceed to: R180 CAH diagnostic test (including single gene sequencing and multiplex ligation-dependent probe amplification (MLPA) of CYP21A2); and/or R388 Linkage testing for congenital adrenal hyperplasia. […] If the underlying diagnosis is still unclear after aneuploidy testing, biochemical investigations and a CAH diagnostic test (where relevant), proceed to: R146 Differences in sex development. This includes microarray and gene panel sequencing.

• #23 Ambiguous Genitalia | Doctor

  https://patient.info/doctor/ambiguous-genitalia

  Ambiguous genitalia may be a result of a disorder of sexual development (DSD), previously called intersex conditions. […] The ability to diagnose these conditions has improved greatly in recent years, due to advances in molecular genetics. […] Prompt, accurate diagnosis and counselling about therapeutic options should be available to parents soon after the baby’s birth. […] To make a diagnosis, it is essential not only to understand normal development but also to understand the different pathophysiological mechanisms responsible for DSDs. […] This should be made with great care and after proper diagnostic work-up which should include external appearance, internal anatomy, genetic make-up and hormone profile. […] The authors of one study commented that despite thorough investigation, in as many as 50% of cases of 46, XY DSD a definitive diagnosis could not be made. […] Referral and consultation between specialties (for example, geneticists, neonatologists, paediatric and adult endocrinologists, gynaecologists, psychologists, ethicists and social workers).

• #24 Intersex – Wikipedia

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

  The common pathway of sexual differentiation, where a productive human female has an XX chromosome pair, and a productive male has an XY pair, is relevant to the development of intersex conditions. […] Ambiguous genitalia is the most common sign. […] There are a variety of symptoms that can occur. […] Intersex can be divided into four categories which are: 46, XX intersex; 46, XY intersex; true gonadal intersex; and complex or undetermined intersex. […] Medical interventions take place to address physical health concerns and psychosocial risks. […] Both types of rationale are the subject of debate, particularly as the consequences of surgical (and many hormonal) interventions are lifelong and irreversible. […] There remains no clinical consensus about an evidence base, surgical timing, necessity, type of surgical intervention, and degree of difference warranting intervention.

• #25 Ambiguous genitalia and disorders of sexual development (DSD)

  https://www.utmb.edu/pedi_ed/CoreV2/Endocrine/Endocrine7.html

  Ambiguous genitalia and disorders of sexual development (DSD) […] Disorders of sexual development can be associated with ambiguous genitalia (i.e., external genitals neither appearing clearly male nor female). […] The most common DSDs are: Klinefelter Syndrome, Turner Syndrome, Mixed gonadal dysgenesis, Congenital adrenal hyperplasia (CAH), Androgen insensitivity syndrome, Cryptorchidism. […] Diagnosis: High FSH and LH, low AMH and inhibin B, testosterone low in 50-75% of cases. […] Diagnosis: prenatal typically. Based on cardiac anomalies, short stature in childhood, delayed puberty (high FSH LH) in puberty. […] Diagnosis: In 21-hydroxylase deficiency, newborn screen (NBS) detects most cases. If no NBS in place, classic type can present with hyponatremia, hyperkalemia, low aldosterone, high PRA, high 17-hydroxy progesterone, high androstenedione.

• #25 Ambiguous genitalia and disorders of sexual development (DSD)

  https://www.utmb.edu/pedi_ed/CoreV2/Endocrine/Endocrine7.html

  Diagnosis: age-appropriate testosterone levels, elevated LH FSH, normally formed testes, absent/vestigial Mullerian structures, variable presence of Wolffian ducts. […] Cryptorchidism mean that the testis is not in the scrotum and is not descended by 4 months old. This is the most common congenital abnormality in boys, present in 2-4% of term male infants.

• #26 Differences of Sex Development: Detection & Diagnosis | Lurie Children’s

  https://www.luriechildrens.org/en/specialties-conditions/atypical-genitalia-differences-of-sex-development/detection-diagnosis/

  Increasingly, parents may learn of a possible DSD before birth. […] Some healthy children are born with genitalia that is not clearly male or female. This situation is referred to as atypical (or ambiguous) genitalia. […] For a newborn, the process of diagnosing the specific condition and determining medical needs begins right after birth. […] A DSD can also be found after infancy. […] Diagnosing differences of sex development and planning healthcare involves many specialists. […] We implement a comprehensive approach to diagnosis, including a physical examination and clinical testing to understand the body both internally and externally. […] For infants, these tests and exams help the team, in collaboration with the childs parents, to make a sex designation (as a boy or girl).

• #27 Prenatal ultrasound finding of atypical genitalia: Counseling, genetic testing and outcomes – PubMed

  https://pubmed.ncbi.nlm.nih.gov/35808910/

  Objective: To report uptake of genetic counseling (GC) and prenatal genetic testing after the finding of atypical genitalia on prenatal ultrasound (US) and the clinical and genetic findings of these pregnancies. […] Atypical genitalia were postnatally confirmed in 91% (group 1) and 64% (group 2), indicating a high rate of false positive US diagnosis of ambiguous genitalia. […] For optimal care, referral for an expert fetal US scan, GC and invasive diagnostics including broad testing should be offered after prenatal detection of isolated atypical genitalia.

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• #29 Atypical Genitalia: Prenatal Ultrasound, Follow-Up Counseling and Diagnosis – The ObG Project

  https://www.obgproject.com/2022/07/22/atypical-genitalia-prenatal-ultrasound-follow-up-counseling-and-diagnosis/

  Atypical Genitalia: Prenatal Ultrasound, Follow-Up Counseling and Diagnosis […] van Bever at al. (Prenatal Diagnosis, 2022) report on the uptake of genetic counseling, diagnostic testing and genetic findings following the identification of atypical genitalia on prenatal ultrasound […] Upon ultrasound diagnosis of fetal atypical genitalia, expert US screening and invasive diagnostic testing, including CMA and gene panel analysis, should be offered in the context of counseling by a clinical geneticist, irrespective of the presence of concurrent US anomalies.

• #30 The Fetal Medicine Foundation

  https://fetalmedicine.org/education/fetal-abnormalities/genital-tract/ambiguous-genitalia

  Ambiguous genitalia […] Prevalence: 1 in 5,000 births. […] Ultrasound diagnosis: […] On the basis of the cause, the condition is divided into: […] Investigations: Detailed ultrasound examination. […] Determine genetic sex by invasive testing or cfDNA in maternal blood. […] Follow up: In families with congenital adrenal hyperplasia, administering dexamethasome to the pregnant woman from 6 weeks gestation can minimize the effect of androgens on the genitalia and the developing brain. […] Prognosis: Treatment of a neonate with ambiguous genitalia should be performed by a multidisciplinary team, including geneticists, pediatric endocrinologists, and pediatric urologist. There is controversy concerning sex assignment and the need or not of reconstructive surgery.

• #31 Ambiguous Genitalia | Radiology Key

  https://radiologykey.com/ambiguous-genitalia/

  Ambiguous genitalia is a morphologic diagnosis, with various underlying genetic and hormonal etiologies. […] Timely diagnosis in the postnatal period is important because of the life-threatening consequences of the classic salt-wasting form. […] In cases of ambiguous genitalia, invasive diagnosis with chorionic villus sampling (CVS) or amniocentesis can be helpful in reconciling ultrasound (US) findings, determining genetic sex, and diagnosing CAH. […] For both medical and psychologic reasons, ambiguous genitalia in a newborn requires timely diagnosis and management. […] Ambiguous genitalia, a subclassification of the disorders of sex development (DSDs), is defined as the unclear appearance of the fetal external genitalia, leading to unsuccessful phenotypic determination of fetal sex.

• #32 Atypical Genitalia | Cardinal Glennon

  https://www.ssmhealth.com/cardinal-glennon/fetal-care-institute/fetal-conditions-we-treat/kidney-urinary-and-genital/atypical-genitalia

  Atypical genitalia, previously known as ambiguous genitalia, is a condition in which a babys external genitals are not typically formed. […] Atypical genitalia falls into a group of conditions known as differences of sexual development (DSDs), which affect approximately 1 in every 4,500 newborns. […] After delivery, specialists from Urology, Endocrinology and Genetics typically assess babies with atypical genitalia in order to assist with assigning the babys sex as well as to look for any associated conditions that might affect the babys overall well-being. Various tests may be used to help obtain a diagnosis and identify any medical problems that would require immediate or later treatment. […] Our team of specialists will provide more information about potential recommendations for care for your baby after birth. Some individuals with atypical genitalia will need treatments such as hormone therapy or surgery. […] Babies with atypical genitalia are typically stable at birth and able to be delivered normally. […] Our team will perform thorough evaluations and, using that information, work with your family to assign the babys sex.

• #33 Ambiguous Genitalia (Atypical Genitalia) | Children’s Hospital Colorado

  https://www.childrenscolorado.org/conditions-and-advice/conditions-and-symptoms/conditions/ambiguous-genetalia/

  Ambiguous genitalia is also called atypical genitalia. Its considered a disorder or difference of sex development (DSD), a group of conditions (previously called intersex) that occur when biological sex and external genitalia dont match. […] Babies with ambiguous genitalia usually get diagnosed at birth. Their doctor may initially diagnose them based on a physical exam. Your baby may also have tests to confirm the diagnosis, including: […] We use these tests to find the cause of ambiguous genitalia. The tests may also help us better understand your babys potential diagnosis and make decisions about gender. […] The goal of treatment for ambiguous genitalia is to ensure your child has sexual and reproductive function as well as social and psychological well-being. Your childs treatment may include a team of experts, such as pediatric urologists, pediatric endocrinologists, geneticists, psychologists and social workers.

• #34 Infant with Ambiguous Genitalia – Pediatric Endocrine Society

  https://pedsendo.org/clinical-resource/infant-with-ambiguous-genitalia/

  Ambiguous genitalia: including bilateral cryptorchidism, hypospadias with unilateral cryptorchidism, posterior labial fusion Hyperpigmentation […] All cases of ambiguous genitalia are considered an emergency and should be promptly referred to a pediatric endocrinology team with a multidisciplinary approach to these patients. […] Gender assignment is not done until evaluation is completed by the multidisciplinary team. […] While evaluating a child with ambiguous genitalia the primary concern should be […] Is this associated with a life-threatening illness? Congenital adrenal hyperplasia is associated with adrenal insufficiency (and may also be associated with salt wasting), which if not recognized and treated urgently can lead to mortality in the infant. […] Gender of rearing: Ideally a decision about gender of rearing should be made as early as possible but only after appropriate work up in the setting of a multidisciplinary team has been done.

• #35 Ambiguous Genitalia and Disorders of Sexual Differentiation | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/17428

  A finely balanced hormonal milieu is required for normal sexual development; testosterone is necessary to stabilize the Wolffian ducts, while secretion of anti-Mullerian factors is essential for the regression of Mullerian ducts. […] The male external genitalia requires the presence of dihydrotestosterone for normal phenotypic development. […] The incidence of a child with a disorder of sexual development (DSD) is approximately 1 in 1000 to 4500 live births. […] The initial evaluation should include karyotyping, which is usually performed on peripheral leukocytes. […] The absence of the SRY gene in a 46XY karyotype indicates deletion and can result in DSD ranging from ambiguous genitalia to sex reversal. […] Accurate diagnosis is essential; in some cases, diagnosis may be obvious; however, it is prudent to transfer cases to a center experienced in the management of DSDs.

• #35 Ambiguous Genitalia and Disorders of Sexual Differentiation | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/17428

  The management of individuals with disorders of sexual development can be complex. […] The decision for gender assignment should be made upon the best available evidence and considerations of such as type of DSD, prenatal androgen exposure, the possibility of fertility and sexual functionality, and psychosocial factors. […] The basic principles of surgery are to ensure the best cosmetic results, preserve sexual functioning, preserve fertility if possible, and decrease the risk of malignancy in the dysgenetic gonad. […] The most important initial finding on physical examination is the presence and number of gonads. […] A disorder of sex development(DSD) is suspected in any infant who has the physical examination findings of bilateral nonpalpable undescended testes or hypospadias with unilateral undescended testis.

• #36 Ambiguous Genitalia and Disorders of Sexual Differentiation – MD Searchlight

  https://mdsearchlight.com/sexual-health/ambiguous-genitalia-and-disorders-of-sexual-differentiation/

  To try and shed light on the issue, doctors usually kick off their evaluation with a test called karyotyping. Its most often done using peripheral leukocytes, which are a type of white blood cell. This test helps sort patients into three categories: 46XX DSD, 46XY DSD, and mixed chromosome DSD. […] Another important test used in this context is fluorescent in situ hybridization (FISH) for the SRY gene. This gene plays a key role in developing male sex characteristics. […] Its crucial not to overlook potential congenital adrenal hyperplasia (CAH). This is because delayed diagnosis could result in salt-wasting, which can cause significant ill-health and potentially death. […] The type of treatment depends on the patients karyotype and whether the SRY gene is present or not. […] Managing individuals with conditions that affect sexual development can be complicated.

• #36 Ambiguous Genitalia and Disorders of Sexual Differentiation – MD Searchlight

  https://mdsearchlight.com/sexual-health/ambiguous-genitalia-and-disorders-of-sexual-differentiation/

  An accurate diagnosis is essentially important. […] The decision about the individuals gender should be based on available evidence and a thorough consideration of factors such as type of condition, hormone exposure, possible fertility and sexual functioning, and psychosocial aspects. […] Surgical procedures, if deemed necessary, should always aim for optimal cosmetic results, preserving sexual functioning and fertility when possible, and minimizing the risk of cancer in the abnormal gonad (ovary or testis). […] Treatment largely depends on the nature of the condition.

• #37 Ambiguous genitalia: clinical management of adult female with male assigned gender: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-021-02914-2

  Managing an adult with ambiguous external genitalia requiring surgical intervention is extremely rare as patients with various spectra of the disease requiring surgical intervention most probably would have received it during childhood or adolescence. […] The current practice for managing these diseases is an early multidisciplinary approach that often includes early surgical evaluation and possible reconstruction, at most deferring until adolescence. […] Advocates for deferral of surgical intervention raise concern that the influence of high maternal estrogen levels that causes clitoromegaly could be mistaken for male phallus, leading to wrong gender assignment. […] The management of the DSD in this case was focused on first ascertaining the etiological diagnosis. […] A diagnosis of 46, XX DSD secondary to androgen excess was made.

• #38 Management of Atypical Genitalia & Suspected DSD in the Neonate | NHSGGC

  https://clinicalguidelines.scot.nhs.uk/ggc-paediatric-guidelines/ggc-paediatric-guidelines/neonatology/management-of-atypical-genitalia-suspected-dsd-in-the-neonate/

  Disorders of sex development (DSD) are relatively rare conditions with diverse pathophysiology. These conditions are very heterogeneous and can present in a variety of different ways, most commonly with atypical genitalia in the newborn period or as a disorder of puberty in adolescence. […] A child with a suspected DSD may present with one or more of these features: a bifid scrotum, bilateral undescended testes, clitoromegaly (phallus 0.8mm in an apparent female infant), micropenis (phallus 2cm stretched penile length in an apparent male infant), proximal (penoscrotal or perineal) hypospadias, distal or midshaft hypospadias in combination with any of the above features. […] The neonatal consultant on call should be informed about the baby. History and examination should be carried out by an experienced clinician. […] Further investigations to identify the cause of DSD are discussed in Appendix 3 but should not be ordered without discussion with the endocrine team.

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