Materiały źródłowe

• #1 Differences in sex development

  https://www.nhs.uk/conditions/differences-in-sex-development/

  Doctors will check a baby for DSD soon after birth because of signs such as undescended testicles or if a baby’s genitals look different. […] Tests may be done to help get a clear diagnosis and find out whether any immediate treatment is needed. […] Tests may include: a further physical examination of your baby done by a specialist, an ultrasound scan to examine their internal organs, blood tests to check their genes and hormone levels. […] Sometimes a DSD may be diagnosed if an older child does not go through puberty properly. […] Speak to a GP if you have any concerns about your child’s development at puberty. They can refer your child to a specialist. […] A team of specialist healthcare professionals will work with you to understand your child’s condition and offer you and your child support and advice. […] Some people with DSD may need hormone therapy and psychological support. Some may want to think about altering their existing genitals, for example by using vaginal stretch techniques. […] Some people with DSD consider altering the appearance of their genitals by having surgery.

• #2 A clinical algorithm to diagnose differences of sex development – PubMed

  https://pubmed.ncbi.nlm.nih.gov/30803928/

  The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. […] A precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. […] We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies.

• #3 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0042/html?lang=en&srsltid=AfmBOorcCT3DCaqCnBrGU6cp_7hxigklsiPVdh8ESoCUMc2OlOVnwVF-

  The development of female or male sex characteristics occurs during fetal life, when the genetic, gonadal, and internal and external genital sex is determined (female or male). Any discordance among sex determination and differentiation stages results in differences/disorders of sex development (DSD), which are classified based on the sex chromosomes found on the karyotype. […] Diagnosis of DSD requires the involvement of a multidisciplinary team coordinated by a clinician, including a service of biochemistry, clinical, and molecular genetic testing, radiology and imaging, and a service of pathological anatomy. […] Diagnosis of the cause of a DSD is challenging and will depend on the knowledge and skills of each specialist involved, added to the performance of the multidisciplinary team.

• #4 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0042/html?lang=en&srsltid=AfmBOorcCT3DCaqCnBrGU6cp_7hxigklsiPVdh8ESoCUMc2OlOVnwVF-

  Biochemical tests and, especially, hormone determinations, play a crucial role in initial diagnosis of DSD, follow-up, and monitoring of response to treatment. […] The karyotype is essential for DSD categorization into one of the three diagnostic groups based on the sex chromosomes found. The gold-standard method is cytogenetics, although array-complementary genomic hybridization (array-CGH) techniques are increasingly used. […] The most frequent monogenic causes of DSD were identified in the late 20th century with the cloning of the genes codifying proteins that were known to be altered in the clinical and biochemical phenotype.

• #5 Differences of Sex Development (DSD) | Causes, Diagnosis & Care

  https://www.cincinnatichildrens.org/health/d/differences-sexual-development

  Differences of sex development (DSD) describes a group of conditions that occur early in pregnancy in which sex development is not typical. […] DSD affects people throughout the lifespan. While some conditions are discovered at birth, others may be found later, during childhood, puberty or even adulthood. DSD can affect both the genitals on the outside and the reproductive body parts on the inside of the body. […] How are differences of sex development diagnosed? […] The doctors may order tests, such as: […] Karyotype: This is a blood test that looks at all of the bodys chromosomes, including the X and Y chromosomes. […] Genetic testing: This is a blood test to look for changes in the genes that are known to cause DSD. […] Hormone testing: This is a blood test that checks what hormones the gonads are making and how much. […] Pelvic ultrasound: This is an imaging test that looks for the gonads and for a uterus. […] Laparoscopy: This is a surgery using a small camera. The surgeon looks for the reproductive parts inside the body. The surgeon may also take small pieces of tissue.

• #6 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. […] 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. Commonly, a DSD may be diagnosed after a puberty does not occur in a typical way (ex: not starting a menstrual period), if a girl starts to develop characteristics such as facial hair or unexpected growth of the clitoris at puberty, or if a boy starts to have growth of the penis at a young age. […] 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).

• #7 Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development | Journal of Medical Genetics

  https://jmg.bmj.com/content/57/9/581

  We present key points from the updated Dutch-Flemish guideline on comprehensive diagnostics in disorders/differences of sex development (DSD) that have not been widely addressed in the current (inter)national literature. […] The Dutch-Flemish guidelines uniquely address three aspects of DSD. First, we propose an algorithm for counselling and diagnostic evaluation when a DSD is suspected prenatally, a clinical situation that is becoming more common. […] Second, we pay special attention to healthcare professionals not working within a DSD centre as they are often the first to diagnose or suspect a DSD, but are not regularly exposed to DSDs and may have limited experience. […] Third, we discuss the timing of (NGS-based) molecular diagnostics in the initial workup of new patients and in people with a diagnosis made solely on clinical grounds or those who had earlier genetic testing that is not compatible with current state-of-the-art diagnostics.

• #8 Disorders of Sexual Development (DSDs)

  https://my.clevelandclinic.org/health/diseases/disorders-of-sexual-development

  Disorders of sexual development (DSDs) are a range of conditions in which a person has characteristics of both sexes. […] In some cases, healthcare providers can diagnose DSDs at birth. Other types of DSDs arent obvious until puberty or later in adulthood. […] A provider will start with a physical examination. They may also ask to run additional tests like: Pelvic ultrasound or MRI (magnetic resonance imaging). Karyotype test to check for abnormal chromosomes. Genetic test to identify gene mutations. Hormone test to measure hormone levels. […] Depending on the severity of symptoms, a person with a DSD might need: Hormone replacement therapy to induce puberty and reduce the risk of DSD-related health issues like osteoporosis. Reconstructive surgery to change the appearance of the genitals.

• #9 Disorders of Sexual Differentiation | UCSF Department of Urology

  https://urology.ucsf.edu/patient-care/children/genital-anomalies/disorders-of-sex-development

  Disorders of sex development (DSDs) are conditions in which the reproductive organs and genitals do not develop normally. […] How are disorders of sex development diagnosed? […] If sexual organs are ambiguous at birth, a child may receive a diagnosis right away. Other types of DSD do not become apparent until puberty. Partial androgen insensitivity syndrome, for example, is usually diagnosed at birth because the genitals appear different. In complete androgen insensitivity syndrome, the genitals look normal for a female, so the condition may not be picked up until a girl fails to menstruate. […] When a DSD is suspected, tests are used to confirm the diagnosis. These include chromosome analyses, blood tests to measure hormone levels, and imaging studies to examine internal sex organs.

• #10 A guide to differences/disorders of sex development/intersex in children and adolescents

  https://www1.racgp.org.au/ajgp/2020/july/differences-disorders-of-sex-development-intersex

  Initial investigations for genital ambiguity include karyotype and/or rapid polymerase chain reaction or fluorescence in situ hybridisation for Y material, glucose, electrolytes, 17-hydroxyprogesterone (17-OHP), gonadotropins, oestradiol and testosterone. […] Presenting features of DSD in an adolescent may include delayed puberty, primary amenorrhea or virilisation of a phenotypic female. […] Many DSD are caused by variants in genes involved in genital and/or gonadal development or steroid hormone production. Recent advances in molecular genetics have enabled more accurate molecular diagnoses in many individuals, which can then provide guidance on prognosis and potential gonadal malignancy risk for some. […] Surgical decisions remain the most challenging and controversial area in DSD, especially if the surgery is considered irreversible. Functionality, malignancy prevention and cosmetic appearance are all taken into account when considering surgical procedures.

• #11 A guide to differences/disorders of sex development/intersex in children and adolescents

  https://www1.racgp.org.au/ajgp/2020/july/differences-disorders-of-sex-development-intersex

  A major consideration in paediatric decision making is respecting parental views/wishes and the impact on the individual as they become more aware of their diagnosis and involved in decision making. […] Individuals with DSD may present in the newborn period with atypical genitalia, during adolescence with atypical pubertal development, or in adulthood with fertility issues.

• #12 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. […] DSDs, formerly termed intersex conditions, are classified on the basis of genetics and the state of the gonads. […] 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. […] A team or multidisciplinary approach to treatment is essential; thus, gender assignment of a child with a DSD is best made after parents have been counseled by a gender medicine team. […] The diagnosis is suspected antenatally when there is discordance between the phenotypic sex diagnosed on antenatal ultrasonography (US) and the female karyotype on fetal DNA testing. […] Following birth, CAH is diagnosed more often during the evaluation of a 46,XX child with ambiguous genitalia and nonpalpable gonads. […] Diagnosis in 46,XY phenotypic females with complete androgen insensitivity usually occurs after puberty during an evaluation for primary amenorrhea.

• #13 Disorders/Differences of Sex Development Presenting in the Newborn With 46,XY Karyotype

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8100517/

  Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions, resulting in discordance between an individual’s sex chromosomes, gonads, and/or anatomic sex. […] The management of a newborn with suspected 46,XY DSD remains challenging. […] Gender assignment should be avoided prior to expert evaluation and possibly until molecular diagnosis. […] The classic diagnostic approach is time and cost-consuming. Today, a different approach may be considered. […] The first line of investigations must exclude rare life-threatening diseases related to salt wasting crises. […] Then, the new genetic tests should be performed, yielding increased diagnostic performance. […] The challenge for health professionals will lie in integrating specific genetic information with better defined clinical and endocrine phenotypes and in terms of long-term evolution.

• #14 Disorders of Sexual Development (DSDs)

  https://my.clevelandclinic.org/health/diseases/disorders-of-sexual-development

  If your child has a DSD, theyll see several healthcare providers from a range of specialties. Members of your childs medical team might include: Pediatricians. Adolescent medicine physicians. Pediatric endocrinologists. Pediatric urologists. Pediatric gynecologists. Geneticists. Child psychologists. […] Providers diagnose many cases of DSDs at birth. But sometimes, symptoms arent apparent until puberty or adulthood. You should schedule an appointment with a healthcare provider as soon as you suspect something out of the ordinary. They can do a physical examination and run tests to see whats causing your childs symptoms.

• #15 Disorders of Sex Development

  https://www.urology-textbook.com/disorders-sex-development.html

  The current classification of DSD (disorders in sex development) by pediatric endocrinologists (Chicago Consensus Statement) emphasizes the sex chromosome constellation (Hughes et al., 2006): […] Diagnosis of Disorders of Sex Development […] Physical examination: Palpable gonads? Urethral meatus location? Stretched penile length? […] Laboratory tests: Urine and blood tests are used, among others: sodium, potassium, blood gases, cortisol (without and with ACTH stimulation), estradiol, androstenedione, 17-hydroxyprogesterone, testosterone (without and with GnRH stimulation), LH, FSH, and dihydrotestosterone. […] Imaging: Abdominal ultrasonography of the adrenal glands and urinary tract, pelvic ultrasound with search for Mllerian structures (uterus? gonads?). MRI in patients with doubtful findings or unclear diagnosis. Regular imaging of the gonads is necessary in patients with increased tumor risk. […] Genetic testing: Genetic testing includes Karyotyping, molecular karyotyping, or next generation sequencing, depending on the suspected disorder. […] Invasive examinations: Helpful might be cystoscopy, vaginoscopy, diagnostic laparoscopy, or gonadal biopsy.

• #16 Health Library

  https://www.limamemorial.org/m/health-library/HIE%20Multimedia/1/001669

  A team of health care professionals with expertise in DSD will work together to understand and treat a child with DSD and support the family. This team may include neonatologists, geneticists, endocrinologists, and psychiatrists or social workers. The specific treatment will depend on the specific cause of the DSD. Depending on the cause, surgery, hormone replacement, or other treatments are used to treat DSD. […] If you notice that your child has unusual genitalia or sexual development, discuss this with your health care provider.

• #17 Differences/Disorder of Sex Development – Society of Pediatric Psychology

  https://pedpsych.org/fact_sheets/differencesdisorder-sex-development/

  The process of sex development, in which humans begin to develop male or female reproductive anatomy, starts at about six weeks after conception. Differences/disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, and/or anatomic sex is atypical. […] Determining the specific DSD diagnosis is important because some conditions, such as certain forms of congenital adrenal hyperplasia, may be associated with medical problems requiring urgent medical attention. […] In some cases, healthcare providers and parents must engage in the complex process of deciding on the child’s gender of rearing. […] Infants or young children born with atypical genitalia may undergo genital surgery to address either urgent or life-threatening medical issues (e.g., if an outlet for urine is blocked or is not present) or non-urgent issues affecting genital function.

• #18 Differences/Disorder of Sex Development – Society of Pediatric Psychology

  https://pedpsych.org/fact_sheets/differencesdisorder-sex-development/

  Gonadectomy (i.e., removing the gonads) may be considered and is another complex decision in which potential for fertility and the individual’s established gender identity should be considered. […] For some DSD, future gender identity can be more difficult to predict; in these cases, families may be encouraged to postpone gonadectomy or genital surgery until the child is old enough to assert their own gender identity and provide informed assent. […] Pediatric psychologists should also assess for and provide support around these concerns. […] Due to the complex and sensitive nature of the issues surrounding DSD care, referral to a specialized center is strongly encouraged. […] Pediatric psychologists may complete an assessment of the psychosocial needs of the caregivers and/or patient, as developmentally appropriate.

• #19 Genetic diagnosis in XY disorders of sex development – Journal of Pediatric Endocrinology and Diabetes

  https://ispae-jped.com/genetic-diagnosis-in-xy-disorders-of-sex-development/

  The evaluation of a child with atypical genitalia begins with a complete medical history, detailed physical examination, and documentation of the findings systematically using the external genitalia score. […] Karyotyping is an essential investigation in children with DSD. […] Molecular diagnosis ends the diagnostic odyssey for the family and the clinician. […] A molecular diagnosis informs the clinician of hormone production and responsiveness, which can help in choosing appropriate androgen replacement therapy. […] A genetic diagnosis is key to predicting the onset of extragenital features. […] Molecular genetic testing has become crucial for ending diagnostic uncertainty and providing closure to patients and their families.

• #20

  https://biomedres.us/fulltexts/BJSTR.MS.ID.005924.php

  Disorders of sex devolvement (DSD), formerly, known as ambiguous genitalia or intersex disorders, represent a spectrum of congenital conditions in which the chromosomal, gonadal or anatomic sex is atypical. […] The main focus of this article is to understand the various etiologies of DSD, diagnostic approach, and management of infants and children with suspected disorders of sex development (DSD) are discussed. […] The main goal of the management is to reach a correct diagnosis, in a timely manner, to avoid the issue of sex-reassignment and its consequences. Patients with disorders of sex development (DSD), and ambiguous genitalia, should be managed in a highly specialized medical center, where a multi-disciplinary team of specialists capable of managing such disorder is present. […] A complete detailed history is essential for an appropriate diagnosis, which include unexplained deaths, fertility, similar genital ambiguity in the family, hirsutism, amenorrhea, maternal exposure to exogenous medications, containing androgens, such as synthetic progesterone preparation and consanguinity.

• #21 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

  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. […] A clinical staging tool called the Prader scale was developed to describe the external genitalia by the degree of virilization, from unvirilized (normal female genitalia) to complete male virilization with penis-size phallus, complete labial fusion, and meatus on the glans (normal male genitalia). […] Assigning a sex of rearing is a great responsibility and obligation and should not be rushed. […] All of these factors named above must be collectively integrated to formulate the most accurate working diagnosis prior to assigning a sex and gender.

• #22 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. […] 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”. […] Symptoms such as infertility, early menopause, amenorrhea or sudden infant death syndrome (SIDS) could be a sign. Hence, an early check-up should be conducted. […] Peripheral blood is collected for karyotyping. This helps classify the patient in one of the three main categories of DSD: chromosomal variation, gonadal development disorders and abnormal genital development.

• #23 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

  While we have improved our understanding of normal sex development in terms of anatomy and molecular biology of the male and female pathways, our understanding of the defects that can occur along the way is still in process. […] Based on gene mutations and/or metabolic defects identified in human and animal models, we have learned from the spectrum of phenotypes that can make up the term ambiguous genitalia or alternatively, atypical genitalia (AG). […] 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. […] 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.

• #24 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

  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. […] A clinical staging tool called the Prader scale was developed to describe the external genitalia by the degree of virilization, from unvirilized (normal female genitalia) to complete male virilization with penis-size phallus, complete labial fusion, and meatus on the glans (normal male genitalia). […] Assigning a sex of rearing is a great responsibility and obligation and should not be rushed. […] All of these factors named above must be collectively integrated to formulate the most accurate working diagnosis prior to assigning a sex and gender.

• #25 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0042/html?lang=en&srsltid=AfmBOorcCT3DCaqCnBrGU6cp_7hxigklsiPVdh8ESoCUMc2OlOVnwVF-

  Biochemical tests and, especially, hormone determinations, play a crucial role in initial diagnosis of DSD, follow-up, and monitoring of response to treatment. […] The karyotype is essential for DSD categorization into one of the three diagnostic groups based on the sex chromosomes found. The gold-standard method is cytogenetics, although array-complementary genomic hybridization (array-CGH) techniques are increasingly used. […] The most frequent monogenic causes of DSD were identified in the late 20th century with the cloning of the genes codifying proteins that were known to be altered in the clinical and biochemical phenotype.

• #26 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. […] 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”. […] Symptoms such as infertility, early menopause, amenorrhea or sudden infant death syndrome (SIDS) could be a sign. Hence, an early check-up should be conducted. […] Peripheral blood is collected for karyotyping. This helps classify the patient in one of the three main categories of DSD: chromosomal variation, gonadal development disorders and abnormal genital development.

• #27 Current Diagnostic Approaches in the Genetic Diagnosis of Disorders of Sex Development – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/current-diagnostic-approaches-in-the-genetic-diagnosis-of-disorders-of-sex-development/doi/jcrpe.galenos.2024.2024-3-3

  Disorders of sex development (DSD) are a clinically and genetically highly heterogeneous group of congenital disorders. The most accurate and rapid diagnosis may be possible with a complementary multidisciplinary diagnostic approach, including comprehensive clinical, hormonal, and genetic investigations. Rapid and accurate diagnosis of DSD requires urgency in terms of gender selection and management of the case. […] Despite the genetic tests performed in current daily practice, the genetic cause is still not elucidated in a significant proportion of cases. Karyotype analysis can be used as a standard for sex chromosome identification. […] The first step in cases with suspected DSD is to determine the presence of sex chromosome and the SRY gene. Karyotype analysis can be used as a standard for sex chromosome detection. In addition, QF-PCR or FISH analysis can be used to detect the sex chromosome and SRY gene more rapidly and cost-effectively.

• #28 Disorders of sex development – Wikipedia

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

  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. […] Inspection of the genitalia with care and palpation must be conducted with the following points in mind. […] 17-Hydroxyprogesterone can be used to screen for congenital adrenal hyperplasia (CAH). This is commonly found in patients with 46, XX DSD. […] Evaluation of hormones 48 hours after birth.

• #29 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0043/html?lang=en&srsltid=AfmBOooPfyvOuH3xezlPaavfY8o1-ha1OzimKtRd3dPeJuBwtmMnE5Om

  46,XY differences/disorders of sex development (DSD) involve an abnormal gonadal and/or genital (external and/or internal) development caused by lack or incomplete intrauterine virilization, with or without the presence of Mllerian ducts remnants. […] Useful biochemical markers for differential diagnosis of 46,XY DSD include hypothalamic-pituitary-gonadal hormones such as luteinizing and follicle-stimulating hormones (LH and FSH; in baseline or after LHRH stimulation conditions), the anti-Mllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), adrenal and gonadal steroid hormones (including cortisol, aldosterone, testosterone and their precursors, dihydrotestosterone and estradiol) and the pituitary ACTH hormone. […] Different patterns of hormone profiles depend on the etiology and the severity of the underlying disorder and the age of the patient at diagnosis.

• #30 Differences of sex development: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001669.htm

  Differences of sex development (DSD) is a group of conditions in which there is a discrepancy between the external (outside) genitals (penis, scrotum, vulva, labia) and the internal (inside) genitals (testes, vagina, ovaries). Intersex is an older term for DSD. […] Note: The cause of DSD may remain undetermined, even with modern diagnostic techniques. […] The following tests and exams 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, endoscopic exam (to verify the absence or presence of a vagina or cervix), ultrasound or MRI to evaluate whether internal sex organs are present (for example, a uterus).

• #31 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0043/html?lang=en&srsltid=AfmBOooPfyvOuH3xezlPaavfY8o1-ha1OzimKtRd3dPeJuBwtmMnE5Om

  Differential diagnosis of 46,XX or 46,XY DSD requires a multidisciplinary approach, including patient history and clinical, morphological, imaging, biochemical and genetic data. We propose a diagnostic algorithm suitable for a newborn with DSD that focuses mainly on biochemical and genetic data. […] Biochemical work-up in patients with a 46,XY karyotype and discordances in gonadal and/or genital development should include measurements of the hormones involved in testicular development and an evaluation of androgen and anti-Mllerian hormone (AMH) synthesis and action. […] AMH is exclusively secreted by Sertoli cells, and is a good marker of primary testicular dysfunction. […] INHB is also primarily secreted by Sertoli cells, though not exclusively. It is the main inhibitor of pituitary FSH secretion.

• #32 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0043/html?lang=en&srsltid=AfmBOooPfyvOuH3xezlPaavfY8o1-ha1OzimKtRd3dPeJuBwtmMnE5Om

  Differential diagnosis of 46,XX or 46,XY DSD requires a multidisciplinary approach, including patient history and clinical, morphological, imaging, biochemical and genetic data. We propose a diagnostic algorithm suitable for a newborn with DSD that focuses mainly on biochemical and genetic data. […] Biochemical work-up in patients with a 46,XY karyotype and discordances in gonadal and/or genital development should include measurements of the hormones involved in testicular development and an evaluation of androgen and anti-Mllerian hormone (AMH) synthesis and action. […] AMH is exclusively secreted by Sertoli cells, and is a good marker of primary testicular dysfunction. […] INHB is also primarily secreted by Sertoli cells, though not exclusively. It is the main inhibitor of pituitary FSH secretion.

• #33 FloridaHealthFinder | Differences of sex development | Health Encyclopedia | FloridaHealthFinder

  https://quality.healthfinder.fl.gov/health-encyclopedia/HIE/1/001669

  Differences of sex development (DSD) is a group of conditions in which there is a discrepancy between the external (outside) genitals (penis, scrotum, vulva, labia) and the internal (inside) genitals (testes, vagina, ovaries). Intersex is an older term for DSD. […] Note: The cause of DSD may remain undetermined, even with modern diagnostic techniques. […] The following tests and exams 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 […] Endoscopic exam (to verify the absence or presence of a vagina or cervix) […] Ultrasound or MRI to evaluate whether internal sex organs are present (for example, a uterus).

• #34 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. […] Chromosomal analysis is a basic examination. The diagnosis is evident if a difference (disorder) of sex development (DSD) is caused by chromosomal abnormalities. Chromosomal analysis allows for the differentiation of 46,XX and 46,XX DSD, which can guide further diagnostic testing. […] Hormonal diagnostics and serum electrolytes/chemistry levels are essential right after birth. These tests mainly aim at excluding a salt-wasting form of CAH. Basic values to be determined include 17-hydroxyprogesterone, cortisol, estradiol, androstenedione, testosterone, and dihydrotestosterone. […] 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.

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

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

  The hCG stimulation test can also help to diagnose 5-alpha-reductase deficiency and distinguish impaired testosterone synthesis from androgen insensitivity. […] A complete ultrasonographic (US) examination of the pelvic structures, as well as the perineal region and of the entire urinary tract, is recommended. […] Pelvic US is helpful for precisely defining the mllerian anatomy, and it can be helpful for evaluating the location and anatomy of nonpalpable gonads. […] 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. Ideally, bilateral deep and longitudinal biopsies are required for optimal histologic evaluation. […] Histologic analysis of gonadal biopsy specimens may identify ovarian tissue, testicular tissue, ovotestes, or streak gonads.

• #36 In-depth exploration of differences of sex development: 5-year experience in a tertiary center in: Endocrine Connections Volume 13 Issue 10 (2024)

  https://ec.bioscientifica.com/view/journals/ec/13/10/EC-24-0236.xml

  In Morocco, there are no national guidelines for diagnosing and managing DSD. […] The appropriate diagnosis was determined through a combination of a medical history review of the physical examination, karyotype evaluation, hormonal levels, serum electrolytes, and radiological findings. […] We categorized our patients into two primary groups based on their karyotypes: those with 46,XY DSD and those with 46,XX DSD. […] In the 46,XX DSD group, the diagnosis of the salt-wasting (SW) form of 21OH deficiency was based on the findings of SW syndrome (abnormal serum electrolytes), atypical genitalia, and a basal 17-hydroxyprogesterone (17OHP) level above 10 ng/mL. […] In the 46,XY DSD group, prepubertal patients underwent the human chorionic gonadotrophin (hCG) stimulation test. […] The diagnosis of androgen insensitivity syndrome (AIS) was suspected.

• #37 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0043/html?lang=en&srsltid=AfmBOooPfyvOuH3xezlPaavfY8o1-ha1OzimKtRd3dPeJuBwtmMnE5Om

  46,XY differences/disorders of sex development (DSD) involve an abnormal gonadal and/or genital (external and/or internal) development caused by lack or incomplete intrauterine virilization, with or without the presence of Mllerian ducts remnants. […] Useful biochemical markers for differential diagnosis of 46,XY DSD include hypothalamic-pituitary-gonadal hormones such as luteinizing and follicle-stimulating hormones (LH and FSH; in baseline or after LHRH stimulation conditions), the anti-Mllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), adrenal and gonadal steroid hormones (including cortisol, aldosterone, testosterone and their precursors, dihydrotestosterone and estradiol) and the pituitary ACTH hormone. […] Different patterns of hormone profiles depend on the etiology and the severity of the underlying disorder and the age of the patient at diagnosis.

• #38 Differences of Sex Development (DSD) Panel Test – PreventionGenetics

  https://www.preventiongenetics.com/testInfo?val=Differences-of-Sex-Development-%28DSD%29-Panel

  Candidates for this test are individuals with symptoms of disorders of sex development including both non-syndromic DSD with ambiguous or abnormal genitalia and syndromic conditions that involve additional congenital anomalies. […] Clinical management of DSD is often difficult and currently only 13% patients receive an accurate clinical genetic diagnosis. An accurate diagnosis is critical to predict the occurrence of life-threatening crises, response to hormone replacement therapy, eventual gender, fertility, and recurrence risk. […] Genetic testing to detect large cytogenetic events and CNVs is recommended in the case of a patient with ambiguous genitalia or other suspected disorder of sex development. Our CNV analysis enables these large cytogenetic abnormalities as well as exon level CNVs to be identified from NGS data. […] This panel analyzes genes involved in both syndromic and non-syndromic Disorders of Sex Development (DSD). 64 genes in this panel have provided genetic diagnosis in 35%-43% of patients with 46,XY DSD and in 17% of patients with 46,XX DSD.

• #39 Current Diagnostic Approaches in the Genetic Diagnosis of Disorders of Sex Development – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/current-diagnostic-approaches-in-the-genetic-diagnosis-of-disorders-of-sex-development/doi/jcrpe.galenos.2024.2024-3-3

  Disorders of sex development (DSD) are a clinically and genetically highly heterogeneous group of congenital disorders. The most accurate and rapid diagnosis may be possible with a complementary multidisciplinary diagnostic approach, including comprehensive clinical, hormonal, and genetic investigations. Rapid and accurate diagnosis of DSD requires urgency in terms of gender selection and management of the case. […] Despite the genetic tests performed in current daily practice, the genetic cause is still not elucidated in a significant proportion of cases. Karyotype analysis can be used as a standard for sex chromosome identification. […] The first step in cases with suspected DSD is to determine the presence of sex chromosome and the SRY gene. Karyotype analysis can be used as a standard for sex chromosome detection. In addition, QF-PCR or FISH analysis can be used to detect the sex chromosome and SRY gene more rapidly and cost-effectively.

• #40 Current Diagnostic Approaches in the Genetic Diagnosis of Disorders of Sex Development – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/current-diagnostic-approaches-in-the-genetic-diagnosis-of-disorders-of-sex-development/doi/jcrpe.galenos.2024.2024-3-3

  Disorders of sex development (DSD) are a clinically and genetically highly heterogeneous group of congenital disorders. The most accurate and rapid diagnosis may be possible with a complementary multidisciplinary diagnostic approach, including comprehensive clinical, hormonal, and genetic investigations. Rapid and accurate diagnosis of DSD requires urgency in terms of gender selection and management of the case. […] Despite the genetic tests performed in current daily practice, the genetic cause is still not elucidated in a significant proportion of cases. Karyotype analysis can be used as a standard for sex chromosome identification. […] The first step in cases with suspected DSD is to determine the presence of sex chromosome and the SRY gene. Karyotype analysis can be used as a standard for sex chromosome detection. In addition, QF-PCR or FISH analysis can be used to detect the sex chromosome and SRY gene more rapidly and cost-effectively.

• #41 Current Diagnostic Approaches in the Genetic Diagnosis of Disorders of Sex Development – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/current-diagnostic-approaches-in-the-genetic-diagnosis-of-disorders-of-sex-development/doi/jcrpe.galenos.2024.2024-3-3

  Disorders of sex development (DSD) are a clinically and genetically highly heterogeneous group of congenital disorders. The most accurate and rapid diagnosis may be possible with a complementary multidisciplinary diagnostic approach, including comprehensive clinical, hormonal, and genetic investigations. Rapid and accurate diagnosis of DSD requires urgency in terms of gender selection and management of the case. […] Despite the genetic tests performed in current daily practice, the genetic cause is still not elucidated in a significant proportion of cases. Karyotype analysis can be used as a standard for sex chromosome identification. […] The first step in cases with suspected DSD is to determine the presence of sex chromosome and the SRY gene. Karyotype analysis can be used as a standard for sex chromosome detection. In addition, QF-PCR or FISH analysis can be used to detect the sex chromosome and SRY gene more rapidly and cost-effectively.

• #42 Management guidelines for disorders/different sex development (DSD) | Anales de Pediatría

  https://www.analesdepediatria.org/en-management-guidelines-for-disorders-different-sex-articulo-S2341287918301637

  Disorders of sex development (DSD) include a wide range of anomalies among the chromosomal, gonadal, and phenotypic (genital) characteristics that define sexual differentiation. […] The diagnosis and treatment of DSD always requires multidisciplinary medical and psychosocial care. An aetiological diagnosis needs the interaction of clinical, biochemical (hormonal), genetic, imaging and, sometimes, surgical examinations. […] The recommended approach to the diagnosis of any suspected DSD now follows, although some of the diagnostic tests are used exclusively in the assessment of newborns with genital ambiguity. […] The diagnosis should be made by a multidisciplinary team. […] The different molecular studies are used to assess for a variety of genetic disorders: Detection of pathogenic changes in the sequence of a gene: the classic Sanger sequencing technique is used when there is a clear candidate gene.

• #43 Differences of Sex Development – Clinical Tree

  https://clinicalpub.com/differences-of-sex-development/

  The availability of exome sequencing in the clinical realm has also ushered in a change in paradigm in DSD diagnosis. With exome sequencing and targeted DSD gene panels available at decreasing cost and with turnaround time similar to that of some endocrine tests, prioritizing genetic testing as the first-tier diagnostic tool for the assessment of DSD patients is quickly becoming a reality in clinical practice. […] DSD can result from anomalies at any stage of these complex developmental pathways. […] Conditions associated with dysgenetic gonads result from events affecting sex determination, while conditions that can cause ambiguous genitalia but are not associated with dysgenetic gonads, such as androgen insensitivity syndrome (AIS) or congenital adrenal hyperplasia (CAH), are considered differences in sexual differentiation.

• #44 Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort | Genome Biology | Full Text

  https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1105-y

  A diagnosis is integral to genetic counseling and family planning and yet it has been found that as few as 13% of patients with a DSD will receive a clinical molecular genetic diagnosis in the current hospital system. […] The process of deploying these genomic assays involves extensive evaluation of technology, bioinformatics, and clinical concerns to choose the right configuration for a given setting. […] We designed a targeted gene panel for DSD using HaloPlex (Agilent) technology. This system allowed us to simultaneously sequence 64 known diagnostic genes for DSD and an additional 967 candidate genes. […] The results from targeted genetic testing of 326 patients with DSD (and 129 of their family members) from a wide spectrum of clinical presentations (the largest known such cohort) are presented.

• #45 Disorders of sex development: advances in genetic diagnosis and challe | AGG

  https://www.dovepress.com/disorders-of-sex-development-advances-in-genetic-diagnosis-and-challen-peer-reviewed-fulltext-article-AGG

  Despite the power of NGS, there are nevertheless several obstacles that usually require to be overcome in a diagnostic laboratory, prior to the introduction of NGS methodology. […] In developed countries, obtaining a molecular diagnosis for a DSD is still only possible in less than half of affected individuals. […] Genomic or exomic sequencing therefore, offers the opportunity to identify additional genes and mechanisms associated with the development of these conditions, to improve diagnostic rates and, ultimately, to have a positive impact on management.

• #46 Disorders of sex development: advances in genetic diagnosis and challe | AGG

  https://www.dovepress.com/disorders-of-sex-development-advances-in-genetic-diagnosis-and-challen-peer-reviewed-fulltext-article-AGG

  The first line investigation of a possible DSD includes quantitative fluorescence-polymerase chain reaction and karyotyping, with respective turnaround times of 12 days and 5 days. […] These investigations are crucial where there is uncertainty about sex assignment but also are an important guide for management where phenotypic sex is apparent. […] The most common sex chromosome DSD is Turner syndrome (45,X) followed by Klinefelter syndrome (47,XXY) and, less commonly, other forms of sex chromosome mosaicism may be identified. […] Detailed chromosome analysis using array comparative genomic hybridization (aCGH) allows the identification of microdeletions or microduplications, below the threshold of visibility by standard karyotype analysis (5 Mb) and is now widely available in optimally resourced centers.

• #47 Disorders of sex development: advances in genetic diagnosis and challe | AGG

  https://www.dovepress.com/disorders-of-sex-development-advances-in-genetic-diagnosis-and-challen-peer-reviewed-fulltext-article-AGG

  It is now recognized that in syndromic and non-syndromic DSD, recurrent, clinically significant regions of copy number variation (CNV) may be found in approximately a fifth of individuals. […] The identification of novel genes involved in DSD as well as insight into developmental mechanisms may be facilitated using aCGH. […] Traditional methods of molecular investigation of DSD include Sanger sequencing, often combined with multiplex ligation-dependent probe amplification to identify abnormalities in the dosage of a gene, such as a gene deletion or duplication. […] The heterogeneous nature, particularly of XY DSD, has led to the grouping of genes into panels that can still be analyzed by these traditional methods. […] Advances in genetic technology, however, combined with an improved understanding of the complex network of genes involved in gonadal development, have led to the use of next generation sequencing (NGS) to permit more rapid analysis of a larger number of genes.

• #48 Disorders of sex development: advances in genetic diagnosis and challe | AGG

  https://www.dovepress.com/disorders-of-sex-development-advances-in-genetic-diagnosis-and-challen-peer-reviewed-fulltext-article-AGG

  It is now recognized that in syndromic and non-syndromic DSD, recurrent, clinically significant regions of copy number variation (CNV) may be found in approximately a fifth of individuals. […] The identification of novel genes involved in DSD as well as insight into developmental mechanisms may be facilitated using aCGH. […] Traditional methods of molecular investigation of DSD include Sanger sequencing, often combined with multiplex ligation-dependent probe amplification to identify abnormalities in the dosage of a gene, such as a gene deletion or duplication. […] The heterogeneous nature, particularly of XY DSD, has led to the grouping of genes into panels that can still be analyzed by these traditional methods. […] Advances in genetic technology, however, combined with an improved understanding of the complex network of genes involved in gonadal development, have led to the use of next generation sequencing (NGS) to permit more rapid analysis of a larger number of genes.

• #49 Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort | Genome Biology | Full Text

  https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1105-y

  Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. […] To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. […] We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. […] Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD.

• #50 Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort | Genome Biology | Full Text

  https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1105-y

  In the 46,XY DSD cohort (278 patients) we found a total of 159 individuals (57%) had a variant in a clinically relevant DSD gene. […] Thus, our panel delivered a probable genetic diagnosis in 43% of individuals affected by 46,XY DSD (the genetic diagnosis rate). […] The targeted gene panel proved less well suited for those affected with 46,XX DSD. Only nine of the 48 patients with 46,XX DSD had a DSD variant, most of which were SRY translocations. […] Our data provide an improved genetic diagnostic rate of 43% for these individuals.

• #51 Caring for individuals with a difference of sex development (DSD): a Consensus Statement | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-018-0010-8

  Although the advent of genome-wide sequencing technologies has improved diagnostics, this goal cannot be achieved in ~50% of individuals with a 46,XY DSD, which highlights the importance of hitherto unidentified regulatory mechanisms. […] To address the aforementioned difficulties, we need to ensure that clinicians who do not have regular exposure to patients with a DSD have detailed guidance in clinical review and data collection for patients at various life stages. […] Standardizing the longitudinal assessment of individuals with a DSD across centres might also provide evidence for or against controversial procedures such as surgical management of genitalia with an atypical appearance. […] The lack of consensus is partially driven by a dearth of relevant, systematic data, which is due to the rarity of the conditions, the heterogeneity of presentations, the loss of patients from follow-up into adulthood and the long interval between surgery and time of data collection.

• #52 Differences in Sex Development | Conditions | UCSF Benioff Children’s Hospitals

  https://www.ucsfbenioffchildrens.org/conditions/differences-in-sex-development

  Differences in sex development, or DSD (previously called intersex), encompasses a range of conditions involving abnormal development of sex organs and ambiguous genitalia (external genital organs that arent clearly male or female). […] In most cases, we know that a child has a difference in sex development by looking at the genitals. In other cases, it’s less clear. Most children are diagnosed at birth, but sometimes the condition isnt detected until adolescence. […] DSD covers a range of conditions, so making a diagnosis requires several tests. The results can shed light on the most appropriate gender to assign your baby. The process may include: A thorough physical exam of external genitalia, Imaging tests (such as MRI, cystogram and ultrasound) of internal reproductive organs, Blood tests that provide information on chromosomes and hormone levels.

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

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

  The hCG stimulation test can also help to diagnose 5-alpha-reductase deficiency and distinguish impaired testosterone synthesis from androgen insensitivity. […] A complete ultrasonographic (US) examination of the pelvic structures, as well as the perineal region and of the entire urinary tract, is recommended. […] Pelvic US is helpful for precisely defining the mllerian anatomy, and it can be helpful for evaluating the location and anatomy of nonpalpable gonads. […] 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. Ideally, bilateral deep and longitudinal biopsies are required for optimal histologic evaluation. […] Histologic analysis of gonadal biopsy specimens may identify ovarian tissue, testicular tissue, ovotestes, or streak gonads.

• #54 Disorders of Sex Development

  https://www.urology-textbook.com/disorders-sex-development.html

  The current classification of DSD (disorders in sex development) by pediatric endocrinologists (Chicago Consensus Statement) emphasizes the sex chromosome constellation (Hughes et al., 2006): […] Diagnosis of Disorders of Sex Development […] Physical examination: Palpable gonads? Urethral meatus location? Stretched penile length? […] Laboratory tests: Urine and blood tests are used, among others: sodium, potassium, blood gases, cortisol (without and with ACTH stimulation), estradiol, androstenedione, 17-hydroxyprogesterone, testosterone (without and with GnRH stimulation), LH, FSH, and dihydrotestosterone. […] Imaging: Abdominal ultrasonography of the adrenal glands and urinary tract, pelvic ultrasound with search for Mllerian structures (uterus? gonads?). MRI in patients with doubtful findings or unclear diagnosis. Regular imaging of the gonads is necessary in patients with increased tumor risk. […] Genetic testing: Genetic testing includes Karyotyping, molecular karyotyping, or next generation sequencing, depending on the suspected disorder. […] Invasive examinations: Helpful might be cystoscopy, vaginoscopy, diagnostic laparoscopy, or gonadal biopsy.

• #55 FloridaHealthFinder | Differences of sex development | Health Encyclopedia | FloridaHealthFinder

  https://quality.healthfinder.fl.gov/health-encyclopedia/HIE/1/001669

  Differences of sex development (DSD) is a group of conditions in which there is a discrepancy between the external (outside) genitals (penis, scrotum, vulva, labia) and the internal (inside) genitals (testes, vagina, ovaries). Intersex is an older term for DSD. […] Note: The cause of DSD may remain undetermined, even with modern diagnostic techniques. […] The following tests and exams 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 […] Endoscopic exam (to verify the absence or presence of a vagina or cervix) […] Ultrasound or MRI to evaluate whether internal sex organs are present (for example, a uterus).

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

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

  The hCG stimulation test can also help to diagnose 5-alpha-reductase deficiency and distinguish impaired testosterone synthesis from androgen insensitivity. […] A complete ultrasonographic (US) examination of the pelvic structures, as well as the perineal region and of the entire urinary tract, is recommended. […] Pelvic US is helpful for precisely defining the mllerian anatomy, and it can be helpful for evaluating the location and anatomy of nonpalpable gonads. […] 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. Ideally, bilateral deep and longitudinal biopsies are required for optimal histologic evaluation. […] Histologic analysis of gonadal biopsy specimens may identify ovarian tissue, testicular tissue, ovotestes, or streak gonads.

• #57 Differences of Sex Development (DSD) | Causes, Diagnosis & Care

  https://www.cincinnatichildrens.org/health/d/differences-sexual-development

  Differences of sex development (DSD) describes a group of conditions that occur early in pregnancy in which sex development is not typical. […] DSD affects people throughout the lifespan. While some conditions are discovered at birth, others may be found later, during childhood, puberty or even adulthood. DSD can affect both the genitals on the outside and the reproductive body parts on the inside of the body. […] How are differences of sex development diagnosed? […] The doctors may order tests, such as: […] Karyotype: This is a blood test that looks at all of the bodys chromosomes, including the X and Y chromosomes. […] Genetic testing: This is a blood test to look for changes in the genes that are known to cause DSD. […] Hormone testing: This is a blood test that checks what hormones the gonads are making and how much. […] Pelvic ultrasound: This is an imaging test that looks for the gonads and for a uterus. […] Laparoscopy: This is a surgery using a small camera. The surgeon looks for the reproductive parts inside the body. The surgeon may also take small pieces of tissue.

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

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

  The hCG stimulation test can also help to diagnose 5-alpha-reductase deficiency and distinguish impaired testosterone synthesis from androgen insensitivity. […] A complete ultrasonographic (US) examination of the pelvic structures, as well as the perineal region and of the entire urinary tract, is recommended. […] Pelvic US is helpful for precisely defining the mllerian anatomy, and it can be helpful for evaluating the location and anatomy of nonpalpable gonads. […] 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. Ideally, bilateral deep and longitudinal biopsies are required for optimal histologic evaluation. […] Histologic analysis of gonadal biopsy specimens may identify ovarian tissue, testicular tissue, ovotestes, or streak gonads.

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

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

  The hCG stimulation test can also help to diagnose 5-alpha-reductase deficiency and distinguish impaired testosterone synthesis from androgen insensitivity. […] A complete ultrasonographic (US) examination of the pelvic structures, as well as the perineal region and of the entire urinary tract, is recommended. […] Pelvic US is helpful for precisely defining the mllerian anatomy, and it can be helpful for evaluating the location and anatomy of nonpalpable gonads. […] 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. Ideally, bilateral deep and longitudinal biopsies are required for optimal histologic evaluation. […] Histologic analysis of gonadal biopsy specimens may identify ovarian tissue, testicular tissue, ovotestes, or streak gonads.

• #60 Differences of Sex Development – Clinical Tree

  https://clinicalpub.com/differences-of-sex-development/

  Overview of the anatomical and biochemical diagnostic differences in DSD, including both disorders of sex determination and disorders of sex differentiation, are presented in the text. […] The major criteria for the diagnosis of pure, partial, or mixed GD are the appearance and histology of both gonads. Therefore, the ultimate diagnosis of any of the forms of GD, particularly the distinction between mixed and partial GD, requires a biopsy of both gonads. […] The risk of gonadoblastoma formation in XY GD increases with age and has been estimated to be as high as 30% by 30 years of age.

• #61 FloridaHealthFinder | Differences of sex development | Health Encyclopedia | FloridaHealthFinder

  https://quality.healthfinder.fl.gov/health-encyclopedia/HIE/1/001669

  Differences of sex development (DSD) is a group of conditions in which there is a discrepancy between the external (outside) genitals (penis, scrotum, vulva, labia) and the internal (inside) genitals (testes, vagina, ovaries). Intersex is an older term for DSD. […] Note: The cause of DSD may remain undetermined, even with modern diagnostic techniques. […] The following tests and exams 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 […] Endoscopic exam (to verify the absence or presence of a vagina or cervix) […] Ultrasound or MRI to evaluate whether internal sex organs are present (for example, a uterus).

• #62 A clinical algorithm to diagnose differences of sex development – PubMed

  https://pubmed.ncbi.nlm.nih.gov/30803928/

  The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. […] A precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. […] We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies.

• #63 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

  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. […] A clinical staging tool called the Prader scale was developed to describe the external genitalia by the degree of virilization, from unvirilized (normal female genitalia) to complete male virilization with penis-size phallus, complete labial fusion, and meatus on the glans (normal male genitalia). […] Assigning a sex of rearing is a great responsibility and obligation and should not be rushed. […] All of these factors named above must be collectively integrated to formulate the most accurate working diagnosis prior to assigning a sex and gender.

• #64 Disorders/Differences of Sex Development Presenting in the Newborn With 46,XY Karyotype

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8100517/

  Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions, resulting in discordance between an individual’s sex chromosomes, gonads, and/or anatomic sex. […] The management of a newborn with suspected 46,XY DSD remains challenging. […] Gender assignment should be avoided prior to expert evaluation and possibly until molecular diagnosis. […] The classic diagnostic approach is time and cost-consuming. Today, a different approach may be considered. […] The first line of investigations must exclude rare life-threatening diseases related to salt wasting crises. […] Then, the new genetic tests should be performed, yielding increased diagnostic performance. […] The challenge for health professionals will lie in integrating specific genetic information with better defined clinical and endocrine phenotypes and in terms of long-term evolution.

• #65 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0043/html?lang=en&srsltid=AfmBOooPfyvOuH3xezlPaavfY8o1-ha1OzimKtRd3dPeJuBwtmMnE5Om

  The biochemistry workup will encompass general analytics, protein and steroids hormones in blood and/or urine samples obtained in baseline conditions or in the context of dynamic stimulation tests according to the patients age. […] Genetic testing starts with a karyotype followed by molecular testing if a monogenic etiology is suspected.

• #66 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0043/html?lang=en&srsltid=AfmBOooPfyvOuH3xezlPaavfY8o1-ha1OzimKtRd3dPeJuBwtmMnE5Om

  46,XY differences/disorders of sex development (DSD) involve an abnormal gonadal and/or genital (external and/or internal) development caused by lack or incomplete intrauterine virilization, with or without the presence of Mllerian ducts remnants. […] Useful biochemical markers for differential diagnosis of 46,XY DSD include hypothalamic-pituitary-gonadal hormones such as luteinizing and follicle-stimulating hormones (LH and FSH; in baseline or after LHRH stimulation conditions), the anti-Mllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), adrenal and gonadal steroid hormones (including cortisol, aldosterone, testosterone and their precursors, dihydrotestosterone and estradiol) and the pituitary ACTH hormone. […] Different patterns of hormone profiles depend on the etiology and the severity of the underlying disorder and the age of the patient at diagnosis.

• #67 Disorders of Sex Development

  https://www.urology-textbook.com/disorders-sex-development.html

  The current classification of DSD (disorders in sex development) by pediatric endocrinologists (Chicago Consensus Statement) emphasizes the sex chromosome constellation (Hughes et al., 2006): […] Diagnosis of Disorders of Sex Development […] Physical examination: Palpable gonads? Urethral meatus location? Stretched penile length? […] Laboratory tests: Urine and blood tests are used, among others: sodium, potassium, blood gases, cortisol (without and with ACTH stimulation), estradiol, androstenedione, 17-hydroxyprogesterone, testosterone (without and with GnRH stimulation), LH, FSH, and dihydrotestosterone. […] Imaging: Abdominal ultrasonography of the adrenal glands and urinary tract, pelvic ultrasound with search for Mllerian structures (uterus? gonads?). MRI in patients with doubtful findings or unclear diagnosis. Regular imaging of the gonads is necessary in patients with increased tumor risk. […] Genetic testing: Genetic testing includes Karyotyping, molecular karyotyping, or next generation sequencing, depending on the suspected disorder. […] Invasive examinations: Helpful might be cystoscopy, vaginoscopy, diagnostic laparoscopy, or gonadal biopsy.

• #68 The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

  https://www.degruyterbrill.com/document/doi/10.1515/almed-2021-0042/html?lang=en&srsltid=AfmBOorcCT3DCaqCnBrGU6cp_7hxigklsiPVdh8ESoCUMc2OlOVnwVF-

  Biochemical tests and, especially, hormone determinations, play a crucial role in initial diagnosis of DSD, follow-up, and monitoring of response to treatment. […] The karyotype is essential for DSD categorization into one of the three diagnostic groups based on the sex chromosomes found. The gold-standard method is cytogenetics, although array-complementary genomic hybridization (array-CGH) techniques are increasingly used. […] The most frequent monogenic causes of DSD were identified in the late 20th century with the cloning of the genes codifying proteins that were known to be altered in the clinical and biochemical phenotype.

• #69 Disorders/Differences of Sex Development Presenting in the Newborn With 46,XY Karyotype

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8100517/

  Such advances will permit optimization of counseling of parents and sex assignment. […] The impact of 46,XY DSD in the life of the affected individuals and their families is immense, as these conditions require long-term clinical, endocrinological, and psychological management. […] Early correct diagnosis is a key factor for optimizing quality of life, but true diagnoses based on pathogenetic pathways is still not reached in some individuals, jeopardizing outcome. […] Rational investigations are mandatory in a newborn with 46,XY DSD to avoid repeated and invasive tests in a small baby. […] Therefore, a parallel approach should be considered which may result in a molecular diagnosis. […] The molecular diagnosis will permit more rational sex assignment, recognizing the natural history of the identified 46,XY DSD.

• #70 Current Diagnostic Approaches in the Genetic Diagnosis of Disorders of Sex Development – Journal of Clinical Research in Pediatric Endocrinology

  https://jcrpe.org/articles/current-diagnostic-approaches-in-the-genetic-diagnosis-of-disorders-of-sex-development/doi/jcrpe.galenos.2024.2024-3-3

  Algorithms in current diagnostic flowcharts are often time-consuming, costly, and unsuitable to accurately and rapidly diagnose DSD, which is considered one of the endocrine urgencies. […] Currently, the general recommendation is to report variants categorized as pathogenic, likely pathogenic, and VUS in the gene(s) related to the patient phenotype.

• #71 A guide to differences/disorders of sex development/intersex in children and adolescents

  https://www1.racgp.org.au/ajgp/2020/july/differences-disorders-of-sex-development-intersex

  Initial investigations for genital ambiguity include karyotype and/or rapid polymerase chain reaction or fluorescence in situ hybridisation for Y material, glucose, electrolytes, 17-hydroxyprogesterone (17-OHP), gonadotropins, oestradiol and testosterone. […] Presenting features of DSD in an adolescent may include delayed puberty, primary amenorrhea or virilisation of a phenotypic female. […] Many DSD are caused by variants in genes involved in genital and/or gonadal development or steroid hormone production. Recent advances in molecular genetics have enabled more accurate molecular diagnoses in many individuals, which can then provide guidance on prognosis and potential gonadal malignancy risk for some. […] Surgical decisions remain the most challenging and controversial area in DSD, especially if the surgery is considered irreversible. Functionality, malignancy prevention and cosmetic appearance are all taken into account when considering surgical procedures.

• #72 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. […] 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. Commonly, a DSD may be diagnosed after a puberty does not occur in a typical way (ex: not starting a menstrual period), if a girl starts to develop characteristics such as facial hair or unexpected growth of the clitoris at puberty, or if a boy starts to have growth of the penis at a young age. […] 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).

• #73 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. […] DSDs, formerly termed intersex conditions, are classified on the basis of genetics and the state of the gonads. […] 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. […] A team or multidisciplinary approach to treatment is essential; thus, gender assignment of a child with a DSD is best made after parents have been counseled by a gender medicine team. […] The diagnosis is suspected antenatally when there is discordance between the phenotypic sex diagnosed on antenatal ultrasonography (US) and the female karyotype on fetal DNA testing. […] Following birth, CAH is diagnosed more often during the evaluation of a 46,XX child with ambiguous genitalia and nonpalpable gonads. […] Diagnosis in 46,XY phenotypic females with complete androgen insensitivity usually occurs after puberty during an evaluation for primary amenorrhea.

• #74 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. […] 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. Commonly, a DSD may be diagnosed after a puberty does not occur in a typical way (ex: not starting a menstrual period), if a girl starts to develop characteristics such as facial hair or unexpected growth of the clitoris at puberty, or if a boy starts to have growth of the penis at a young age. […] 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).

• #75 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. […] 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. Commonly, a DSD may be diagnosed after a puberty does not occur in a typical way (ex: not starting a menstrual period), if a girl starts to develop characteristics such as facial hair or unexpected growth of the clitoris at puberty, or if a boy starts to have growth of the penis at a young age. […] 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).

• #76 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

  As a new standard of care according to the consensus statements, this multidisciplinary team should at minimum include representatives from endocrinology, urology (and/or surgery), social work behavioral health (psychology/psychiatry), and nursing, and have access to experts in gynecology, bioethics, neonatology, and child life. […] The need for broad and longitudinal psychological support cannot be overstated. […] Psychological issues can be dynamic along the age scale through infant, childhood, adolescent and adult developmental phases. […] Urgent referral or consultation with pediatric endocrinology (and eventually the entire multidisciplinary team) is essential if genital ambiguity is noted in the neonatal period, in order to expedite an informed sex assignment. […] As such, rapid mobilization of resources is necessary to adequately address the sex/gender determination question.

• #77 Management guidelines for disorders/different sex development (DSD) | Anales de Pediatría

  https://www.analesdepediatria.org/en-management-guidelines-for-disorders-different-sex-articulo-S2341287918301637

  Multidisciplinary teams are unable to establish the aetiology of DSDs in 40% to 50% of cases, especially in patients with a 46,XY karyotype. […] The decision rests with the parents, counselled by a multidisciplinary team (paediatric endocrinologists, surgeons, paediatric urologists, gynaecologists, neonatologists, geneticists, psychologists, social workers etc.). […] The current criteria for gender assignment are based on (1) psychosexual outcomes in adults with an aetiological diagnosis, (2) the potential for fertility, (3) surgical options and (4) the need for hormone replacement therapy during puberty. […] The DSD Guideline presents the most widely approved approach to sex steroid replacement therapy during puberty. […] The decision to choose this approach must be made jointly by the family and the multidisciplinary team advising the family. […] The DSD Guideline details the risk of malignant transformation based on the DSD classification.

• #78 Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort | Genome Biology | Full Text

  https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1105-y

  In the 46,XY DSD cohort (278 patients) we found a total of 159 individuals (57%) had a variant in a clinically relevant DSD gene. […] Thus, our panel delivered a probable genetic diagnosis in 43% of individuals affected by 46,XY DSD (the genetic diagnosis rate). […] The targeted gene panel proved less well suited for those affected with 46,XX DSD. Only nine of the 48 patients with 46,XX DSD had a DSD variant, most of which were SRY translocations. […] Our data provide an improved genetic diagnostic rate of 43% for these individuals.

• #79 Towards improved genetic diagnosis of human differences of sex development | Nature Reviews Genetics

  https://www.nature.com/articles/s41576-021-00365-5

  Despite being collectively among the most frequent congenital developmental conditions worldwide, differences of sex development (DSD) lack recognition and research funding. […] Identification of the individual conditions under the DSD umbrella is challenging and molecular genetic diagnosis is frequently not achieved, which has psychosocial and health-related repercussions for patients and their families. […] New genomic approaches have the potential to resolve this impasse through better detection of protein-coding variants and ascertainment of under-recognized aetiology, such as mosaic, structural, non-coding or epigenetic variants. […] This textbook chapter details clinical DSD categories, aetiology, testing and management approaches. […] This article describes a recent comprehensive clinical algorithm that guides diagnosis and management of newborns with ambiguous genitalia.

• #80 Towards improved genetic diagnosis of human differences of sex development | Nature Reviews Genetics

  https://www.nature.com/articles/s41576-021-00365-5

  Despite being collectively among the most frequent congenital developmental conditions worldwide, differences of sex development (DSD) lack recognition and research funding. […] Identification of the individual conditions under the DSD umbrella is challenging and molecular genetic diagnosis is frequently not achieved, which has psychosocial and health-related repercussions for patients and their families. […] New genomic approaches have the potential to resolve this impasse through better detection of protein-coding variants and ascertainment of under-recognized aetiology, such as mosaic, structural, non-coding or epigenetic variants. […] This textbook chapter details clinical DSD categories, aetiology, testing and management approaches. […] This article describes a recent comprehensive clinical algorithm that guides diagnosis and management of newborns with ambiguous genitalia.

• #81 Breakthrough in diagnosing disorders of sex development – Hudson Institute of Medical Research

  https://www.hudson.org.au/news/breakthrough-in-diagnosing-sex-development-disorders/

  Disorders/differences of sex development (DSD) are difficult to diagnose because of the multiple phenotypes and genes involved, but a new technique developed at Hudson Institute of Medical Research is set to change all that. […] Researchers have developed a technique to reprogram skin cells into testicular cells (Sertoli cells), simplifying the diagnosis of disorders of sex development (DSD) by allowing detailed study and testing without the need for gonadal tissue samples. […] Accurate diagnosis is critical to inform the occurrence of life-threatening crises (e.g. congenital adrenal hyperplasia), the response to hormone replacement therapy, eventual gender identity, cancer risk and counselling for future fertility. […] Patients suffer a long diagnostic odyssey, with many never receiving a definitive diagnosis, Prof Harley said. Our new model will help Identify new causes and mechanisms of DSD in children.

• #82 Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development | Journal of Medical Genetics

  https://jmg.bmj.com/content/57/9/581

  The diagnostic workup that is proposed for 46,XX and 46,XY DSD is shown in figures 2 and 3, respectively. […] Even with the rapidly expanding molecular possibilities, a (family) history and a physical examination remain the essential first steps in the diagnostic process. […] The rapidly evolving diagnostic possibilities raise new questions: What do laboratories report? How should we deal with the frequent findings of mainly unique VUS or class 3 variants (ACMG recommendation) in the many different DSD-related genes in the diagnostic setting? […] Centralised pathological examination of gonadal biopsy and gonadectomy samples in one centre, or a restricted number of centres, on a national scale can help to overcome the problem of non-uniform classification and has proven feasible in the Netherlands and Belgium. […] We therefore believe that uniform assessment and classification of gonadal differentiation patterns should also be addressed in guidelines on DSD management.

• #83

  https://biomedres.us/fulltexts/BJSTR.MS.ID.005924.php

  Although the diagnosis of the various etiological causes of disorders of sex development (DSD) can be delineated through chromosomal analysis, the radiological imaging, and various hormonal studies, the issue of sex assignment in the newborn with ambiguous genitalia is in a state of controversy. […] The assignment depends on many factors, including the genes involved. Despite the significant progress made over recent years in understanding the genetic basis of human sexual development, a specific molecular diagnosis is identified in about 20% of cases of DSD. […] Managing a patient with sexual ambiguity is so complex and challenging and depends on the sex assigned. Hormonal replacement therapy and surgery, all of which are crucial and considered as a part of the care.

• #84 Disorders/Differences of Sex Development Presenting in the Newborn With 46,XY Karyotype

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8100517/

  Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions, resulting in discordance between an individual’s sex chromosomes, gonads, and/or anatomic sex. […] The management of a newborn with suspected 46,XY DSD remains challenging. […] Gender assignment should be avoided prior to expert evaluation and possibly until molecular diagnosis. […] The classic diagnostic approach is time and cost-consuming. Today, a different approach may be considered. […] The first line of investigations must exclude rare life-threatening diseases related to salt wasting crises. […] Then, the new genetic tests should be performed, yielding increased diagnostic performance. […] The challenge for health professionals will lie in integrating specific genetic information with better defined clinical and endocrine phenotypes and in terms of long-term evolution.

• #85 Genetic diagnosis in XY disorders of sex development – Journal of Pediatric Endocrinology and Diabetes

  https://ispae-jped.com/genetic-diagnosis-in-xy-disorders-of-sex-development/

  The evaluation of a child with atypical genitalia begins with a complete medical history, detailed physical examination, and documentation of the findings systematically using the external genitalia score. […] Karyotyping is an essential investigation in children with DSD. […] Molecular diagnosis ends the diagnostic odyssey for the family and the clinician. […] A molecular diagnosis informs the clinician of hormone production and responsiveness, which can help in choosing appropriate androgen replacement therapy. […] A genetic diagnosis is key to predicting the onset of extragenital features. […] Molecular genetic testing has become crucial for ending diagnostic uncertainty and providing closure to patients and their families.

• #86 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

  Evidence based guidelines are badly needed and future studies will help give better guidance for specific conditions and clinical scenarios, though multicenter networks are making progress. […] Parents must be involved and made to feel included in decision-making. […] This approach to complex or difficult health care decisions, called Shared Decision-Making, helps the family feel more invested in the process, and leads to increased satisfaction. […] 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 (generally to mitigate increased risk of malignancy) 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.

• #87 Differences of Sex Development – Clinical Tree

  https://clinicalpub.com/differences-of-sex-development/

  Overview of the anatomical and biochemical diagnostic differences in DSD, including both disorders of sex determination and disorders of sex differentiation, are presented in the text. […] The major criteria for the diagnosis of pure, partial, or mixed GD are the appearance and histology of both gonads. Therefore, the ultimate diagnosis of any of the forms of GD, particularly the distinction between mixed and partial GD, requires a biopsy of both gonads. […] The risk of gonadoblastoma formation in XY GD increases with age and has been estimated to be as high as 30% by 30 years of age.

• #88 Caring for individuals with a difference of sex development (DSD): a Consensus Statement | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-018-0010-8

  The various forms of XY and X/XY DSD have a variable risk of developing a gonadal germ cell cancer, which is further modulated by patient age, location of the gonad and, possibly, genetic predisposition. […] The developmental origin of DSD conditions and the effect they can have on the functioning of several organ systems warrant extensive somatic assessment of all individuals presenting with a DSD, irrespective of age. […] The standardization of somatic assessments is crucial to secure the validity of cross-centre data pooling with the aim of revealing hitherto unrecognized health consequences and outcomes.

• #89 Differences of Sex Development (Intersex) Care | Article | GLOWM

  https://www.glowm.com/article/heading/vol-2–adolescent-gynecology–differences-of-sex-development-intersex-care/id/418293

  In recognition of these issues, the Consensus Statement on Management of Intersex Disorders has emphasized the importance of the role of psychosocial care in the multidisciplinary team management of children with DSD diagnoses. […] Genetics’ evaluation plays a key role in evaluating patients with DSD conditions. […] A karyotype (+/ FISH for SRY gene) is a key first step and can help determine which category of DSD the patient falls under (46,XX DSD, 46,XY DSD or other chromosomal aneuploidy) and direct further evaluation; this test is typically ordered as soon as possible. […] Endocrine testing can be most informative in the time of mini-puberty of infancy or during adolescence, and can provide both diagnostic information and assess hormone/gonadal function. […] Surgical management should be determined with a shared decision-making model that includes the patient’s input whenever possible, which may mean that some surgeries should be delayed so that the patient is able to participate in decision-making. […] Fertility preservation counseling for DSD patients is an important, evolving field that incorporates reproductive science, advancing technology, and ethical considerations.

• #90 Disorders/Differences of Sex Development Presenting in the Newborn With 46,XY Karyotype

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8100517/

  Such advances will permit optimization of counseling of parents and sex assignment. […] The impact of 46,XY DSD in the life of the affected individuals and their families is immense, as these conditions require long-term clinical, endocrinological, and psychological management. […] Early correct diagnosis is a key factor for optimizing quality of life, but true diagnoses based on pathogenetic pathways is still not reached in some individuals, jeopardizing outcome. […] Rational investigations are mandatory in a newborn with 46,XY DSD to avoid repeated and invasive tests in a small baby. […] Therefore, a parallel approach should be considered which may result in a molecular diagnosis. […] The molecular diagnosis will permit more rational sex assignment, recognizing the natural history of the identified 46,XY DSD.

• #91 Management guidelines for disorders/different sex development (DSD) | Anales de Pediatría

  https://www.analesdepediatria.org/en-management-guidelines-for-disorders-different-sex-articulo-S2341287918301637

  Multidisciplinary teams are unable to establish the aetiology of DSDs in 40% to 50% of cases, especially in patients with a 46,XY karyotype. […] The decision rests with the parents, counselled by a multidisciplinary team (paediatric endocrinologists, surgeons, paediatric urologists, gynaecologists, neonatologists, geneticists, psychologists, social workers etc.). […] The current criteria for gender assignment are based on (1) psychosexual outcomes in adults with an aetiological diagnosis, (2) the potential for fertility, (3) surgical options and (4) the need for hormone replacement therapy during puberty. […] The DSD Guideline presents the most widely approved approach to sex steroid replacement therapy during puberty. […] The decision to choose this approach must be made jointly by the family and the multidisciplinary team advising the family. […] The DSD Guideline details the risk of malignant transformation based on the DSD classification.

• #92 Disorders/Differences of Sex Development Presenting in the Newborn With 46,XY Karyotype

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8100517/

  A recent position paper not specific for DSD concluded that early diagnosis of a genetically based endocrine disorder contributes to precise management and helps the patients and their families in their self-determined planning of life. […] Sex assignment is one of the main issues in the management of a newborn with 46,XY DSD. […] The past recommendation for female assignment based on easier surgery has been overcome by improvements in male reconstructive surgical techniques. […] Social and cultural factors may influence decisions on sex assignment and outcome. […] Because the long-term outcome of the early management of babies with 46,XY DSD remains largely based on evidence from small series or single reports, ethical guidelines for the management of infants with DSD must be taken into consideration.

• #93 Differences of Sex Development (DSD) | Ambiguous Genitalia | Duke Health

  https://www.dukehealth.org/pediatric-treatments/pediatric-endocrinology/disorders-of-sex-development

  Children born with differences of sex development may have sex-specific traits that arent clearly male or female. This may be referred to as ambiguous genitalia. […] Hormonal imbalances can include congenital adrenal hyperplasia (CAH), a genetic disorder that affects hormone production in the adrenal glands. […] The first step is understanding your childs condition and determining if it is affecting their physical well-being now or will in the future. […] More often, your childs physical health is not immediately affected, and you and your child will begin a long-term relationship with our gender care specialists. […] In the appropriate setting, surgery to reconstruct ambiguous or atypical genital organs may be indicated. […] Depending on the reason for surgery, genital surgery in infants with primarily male genitalia may be performed between six and 18 months of age.

• #94 Differences of Sex Development (DSD) | Ambiguous Genitalia | Duke Health

  https://www.dukehealth.org/pediatric-treatments/pediatric-endocrinology/disorders-of-sex-development

  We spend months discussing the impact of surgery on your child and help you understand when, how, and if surgery should be considered. […] If there is no physical concern, we often recommend waiting. […] However, if and when you choose surgery for your child, its comforting to know that we are recognized for the depth of our expertise.

• #95 Differences in Sexual Development | Endocrine Society

  https://www.endocrine.org/patient-engagement/endocrine-library/differences-in-sexual-development

  Differences of sexual development are a group of conditions where the biological sex (being male or female) of a baby does not match the genital appearance. […] Diagnosing DSD Changes in genital appearance after birth is usually the first sign of DSD. […] Your child’s doctor will examine your child and ask about your family’s medical history. The doctor will check your child’s chromosomes with a blood test or by scraping the inside of your child’s cheek. […] Extensive genetic testing may also find a faulty gene that can explain the changes in reproductive organ and genital development. […] The goals of management are to ensure your child’s long-term emotional well-being, future sexual function and potential for fertility, and stable gender identity. […] Many children with DSD do not go into puberty on their own and would need sex hormone therapy (i.e. estrogen for those raised as girls or testosterone therapy for those raised as boys), to start and maintain puberty.

• #96 Differences/Disorder of Sex Development – Society of Pediatric Psychology

  https://pedpsych.org/fact_sheets/differencesdisorder-sex-development/

  Psychologists working with children and families affected by DSD conditions must be knowledgeable regarding issues related to sexuality, gender identity, and gender expression, and be comfortable counseling families in these areas. […] Despite limited evidence-based psychosocial interventions for children with DSD and their families, expert opinion suggests that a pediatric psychologist, or other behavioral health provider experienced in DSD, be available to support caregivers as they manage the range of emotions that may accompany a new DSD diagnosis.

• #97 Frequently asked questions about differences of sex development | University of Iowa Health Care Stead Family Children’s Hospital

  https://uihc.org/childrens/health-topics/frequently-asked-questions-about-differences-sex-development

  The Differences of Sex Development Service at UI Stead Family Childrens Hospital treats children, teens, and adults with differences of sex development (DSD), also sometimes referred to as intersex conditions. […] Parents whose children have been diagnosed with a DSD condition have many questions about how the condition is diagnosed and treated. […] Some DSD conditions are discovered at birth, while others may be found during childhood or later in life. […] This means that every patient requires an individual treatment plan specific to their diagnosis and may need attention from several kinds of medical experts. […] No. Sex development is about sexual anatomy reproductive organs and structures and the chromosomes and hormones that determine how those organs and structures develop in the body. A child who has a DSD condition has characteristics of sexual anatomy that are not typical. […] This will depend on the specific DSD condition. Some conditions have no impact on the childs fertility. Others may make becoming a parent a less typical process. […] Discussing this in an open and age-appropriate way will be one of the many ways you support your child.

• #98 Disorders of sex development: Genetic characterization of a patient cohort

  https://www.spandidos-publications.com/10.3892/mmr.2019.10819

  In conclusion, for the etiological diagnosis of DSDs, a broad-spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations. […] The etiological diagnosis of DSDs generally requires a broad spectrum of endocrinological tests, radiological images, and genetic tests. Karyotyping is an initial test that allows for the classification of the disorder, according to Lawson Wilkins, 2006. […] Providing patients with DSDs with a molecular diagnosis allows for the establishment of clinical management techniques, including providing patients with information regarding the risks of neoplasia associated with some types of DSDs, as well as offering advice to the patients and their family members regarding recurrence risks.

• #99 Caring for individuals with a difference of sex development (DSD): a Consensus Statement | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-018-0010-8

  The term differences of sex development (DSDs; also known as disorders of sex development) refers to a heterogeneous group of congenital conditions affecting human sex determination and differentiation. […] Recommendations from 2014, 2015 and 2016 address diagnostic strategies and provide guidance for a holistic clinical approach, mostly during childhood and adolescence. […] All individuals with a suspected DSD need a thorough diagnostic evaluation, including an extensive whole-body and genital physical exam, biochemical and genetic investigations and imaging studies, with results discussed in the multidisciplinary team. The ultimate goal is to obtain a diagnosis at the molecular genetics level to allow prognostic predictions and genetic counselling and to set up an individualized management plan.

• #100 Disorders/Differences of Sex Development Presenting in the Newborn With 46,XY Karyotype

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8100517/

  Each subject with 46,XY DSD should receive individualized care by an expert multidisciplinary team. […] Support groups may be invaluable to individuals with 46,XY DSD and their families. […] The care of people with DSD quickly evolves as knowledge in this field accrues, but the birth of a baby with 46,XY DSD is still perceived as a social rather than a true medical emergency. […] Improvements are needed on diagnostic schemes in the first days of life as well as objective criteria to assign sex, to predict the risk of germ cell cancers and unnecessary gonadal removal, and to optimize surgical procedures and future fertility options.

• #101 Caring for individuals with a difference of sex development (DSD): a Consensus Statement | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-018-0010-8

  The term differences of sex development (DSDs; also known as disorders of sex development) refers to a heterogeneous group of congenital conditions affecting human sex determination and differentiation. […] Recommendations from 2014, 2015 and 2016 address diagnostic strategies and provide guidance for a holistic clinical approach, mostly during childhood and adolescence. […] All individuals with a suspected DSD need a thorough diagnostic evaluation, including an extensive whole-body and genital physical exam, biochemical and genetic investigations and imaging studies, with results discussed in the multidisciplinary team. The ultimate goal is to obtain a diagnosis at the molecular genetics level to allow prognostic predictions and genetic counselling and to set up an individualized management plan.

• #102 apem :: Annals of Pediatric Endocrinology & Metabolism

  https://e-apem.org/m/journal/view.php?number=886

  Optimal care for patients with a suspected DSD is best provided by an experienced clinical team with adequate knowledge about the range of conditions associated with DSDs. […] The investigative work-up should include LH, FSH, estradiol, and testosterone and ultrasound of the pelvis should be performed by an experienced sonologist. Karyotyping should be done if either the gonadotropins are raised or the uterus is absent. […] It is recommended that DSD cases should be treated at specialized centers by an experienced multidisciplinary team prepared to deal not only with the diagnostic investigation but also all subsequent aspects of therapy.

• #103 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

  As a new standard of care according to the consensus statements, this multidisciplinary team should at minimum include representatives from endocrinology, urology (and/or surgery), social work behavioral health (psychology/psychiatry), and nursing, and have access to experts in gynecology, bioethics, neonatology, and child life. […] The need for broad and longitudinal psychological support cannot be overstated. […] Psychological issues can be dynamic along the age scale through infant, childhood, adolescent and adult developmental phases. […] Urgent referral or consultation with pediatric endocrinology (and eventually the entire multidisciplinary team) is essential if genital ambiguity is noted in the neonatal period, in order to expedite an informed sex assignment. […] As such, rapid mobilization of resources is necessary to adequately address the sex/gender determination question.

• #104 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

  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. […] A clinical staging tool called the Prader scale was developed to describe the external genitalia by the degree of virilization, from unvirilized (normal female genitalia) to complete male virilization with penis-size phallus, complete labial fusion, and meatus on the glans (normal male genitalia). […] Assigning a sex of rearing is a great responsibility and obligation and should not be rushed. […] All of these factors named above must be collectively integrated to formulate the most accurate working diagnosis prior to assigning a sex and gender.

• #105 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

  Evidence based guidelines are badly needed and future studies will help give better guidance for specific conditions and clinical scenarios, though multicenter networks are making progress. […] Parents must be involved and made to feel included in decision-making. […] This approach to complex or difficult health care decisions, called Shared Decision-Making, helps the family feel more invested in the process, and leads to increased satisfaction. […] 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 (generally to mitigate increased risk of malignancy) 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.

• #106 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

  As a new standard of care according to the consensus statements, this multidisciplinary team should at minimum include representatives from endocrinology, urology (and/or surgery), social work behavioral health (psychology/psychiatry), and nursing, and have access to experts in gynecology, bioethics, neonatology, and child life. […] The need for broad and longitudinal psychological support cannot be overstated. […] Psychological issues can be dynamic along the age scale through infant, childhood, adolescent and adult developmental phases. […] Urgent referral or consultation with pediatric endocrinology (and eventually the entire multidisciplinary team) is essential if genital ambiguity is noted in the neonatal period, in order to expedite an informed sex assignment. […] As such, rapid mobilization of resources is necessary to adequately address the sex/gender determination question.

• #107 Caring for individuals with a difference of sex development (DSD): a Consensus Statement | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-018-0010-8

  Although the advent of genome-wide sequencing technologies has improved diagnostics, this goal cannot be achieved in ~50% of individuals with a 46,XY DSD, which highlights the importance of hitherto unidentified regulatory mechanisms. […] To address the aforementioned difficulties, we need to ensure that clinicians who do not have regular exposure to patients with a DSD have detailed guidance in clinical review and data collection for patients at various life stages. […] Standardizing the longitudinal assessment of individuals with a DSD across centres might also provide evidence for or against controversial procedures such as surgical management of genitalia with an atypical appearance. […] The lack of consensus is partially driven by a dearth of relevant, systematic data, which is due to the rarity of the conditions, the heterogeneity of presentations, the loss of patients from follow-up into adulthood and the long interval between surgery and time of data collection.

• #108 Differences of Sex Development (DSD) Panel Test – PreventionGenetics

  https://www.preventiongenetics.com/testInfo?val=Differences-of-Sex-Development-%28DSD%29-Panel

  Candidates for this test are individuals with symptoms of disorders of sex development including both non-syndromic DSD with ambiguous or abnormal genitalia and syndromic conditions that involve additional congenital anomalies. […] Clinical management of DSD is often difficult and currently only 13% patients receive an accurate clinical genetic diagnosis. An accurate diagnosis is critical to predict the occurrence of life-threatening crises, response to hormone replacement therapy, eventual gender, fertility, and recurrence risk. […] Genetic testing to detect large cytogenetic events and CNVs is recommended in the case of a patient with ambiguous genitalia or other suspected disorder of sex development. Our CNV analysis enables these large cytogenetic abnormalities as well as exon level CNVs to be identified from NGS data. […] This panel analyzes genes involved in both syndromic and non-syndromic Disorders of Sex Development (DSD). 64 genes in this panel have provided genetic diagnosis in 35%-43% of patients with 46,XY DSD and in 17% of patients with 46,XX DSD.

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