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Endocrine Practice : Official Journal... Dec 2019
Topics: 46, XX Disorders of Sex Development; Aged; Humans; Male
PubMed: 31013161
DOI: 10.4158/EP-2019-0060 -
Pediatric Radiology Apr 2022When infants are identified with a difference of sex development (DSD), a thoughtful approach to imaging is essential to appropriate clinical management. This review... (Review)
Review
When infants are identified with a difference of sex development (DSD), a thoughtful approach to imaging is essential to appropriate clinical management. This review provides a comprehensive guide for radiologists who are tasked with performing this critical assignment. We review the embryologic basis of DSDs, with attention to the imaging findings that can indicate specific diagnoses. We also discuss techniques for optimal imaging, including strategies for identifying the gonads by US, tactics for performing genitograms with fluoroscopy and contrast-enhanced US, and the appropriate utilization of MRI. Finally, we review the clinical data and imaging findings that characterize some of the most common DSDs, including congenital adrenal hyperplasia, complete androgen insensitivity syndrome and gonadal dysgenesis.
Topics: Adrenal Hyperplasia, Congenital; Disorders of Sex Development; Female; Humans; Infant; Male; Radiologists; Sexual Development; Turner Syndrome
PubMed: 34355264
DOI: 10.1007/s00247-021-05147-z -
International Journal of Molecular... Dec 2019Androgens and anti-Müllerian hormone (AMH), secreted by the foetal testis, are responsible for the development of male reproductive organs and the regression of female... (Review)
Review
Androgens and anti-Müllerian hormone (AMH), secreted by the foetal testis, are responsible for the development of male reproductive organs and the regression of female anlagen. Virilization of the reproductive tract in association with the absence of Müllerian derivatives in the XX foetus implies the existence of testicular tissue, which can occur in the presence or absence of SRY. Recent advancement in the knowledge of the opposing gene cascades driving to the differentiation of the gonadal ridge into testes or ovaries during early foetal development has provided insight into the molecular explanation of XX maleness.
Topics: Animals; Disorders of Sex Development; Fetus; Humans; Male; Mammals; Models, Biological; Sex Differentiation
PubMed: 31816857
DOI: 10.3390/ijms20236089 -
Biomolecules Apr 2023Gonadal development is the first step in human reproduction. Aberrant gonadal development during the fetal period is a major cause of disorders/differences of sex... (Review)
Review
Gonadal development is the first step in human reproduction. Aberrant gonadal development during the fetal period is a major cause of disorders/differences of sex development (DSD). To date, pathogenic variants of three nuclear receptor genes (, , and ) have been reported to cause DSD via atypical testicular development. In this review article, we describe the clinical significance of the variants as the cause of DSD and introduce novel findings from recent studies. variants are associated with 46,XY DSD and 46,XX testicular/ovotesticular DSD. Notably, both 46,XX DSD and 46,XY DSD caused by the variants show remarkable phenotypic variability, to which digenic/oligogenic inheritances potentially contribute. Additionally, we discuss the roles of and in the etiology of DSD. acts as an anti-testicular gene. Duplications containing result in 46,XY DSD, whereas deletions encompassing can underlie 46,XX testicular/ovotesticular DSD. has recently been reported as a causative gene for 46,XX testicular/ovotesticular DSD and possibly for 46,XY DSD, although the role of in gonadal development is unclear. The knowledge about these three nuclear receptors provides novel insights into the molecular networks involved in the gonadal development in human fetuses.
Topics: Humans; Male; Disorder of Sex Development, 46,XY; Mutation; Ovotesticular Disorders of Sex Development; Phenotype; Sexual Development; Testis; Receptors, Cytoplasmic and Nuclear
PubMed: 37189438
DOI: 10.3390/biom13040691 -
Sexual Development : Genetics,... 2022SOX genesare master regulatory genes controlling development and are fundamental to the establishment of sex determination in a multitude of organisms. The discovery of... (Review)
Review
SOX genesare master regulatory genes controlling development and are fundamental to the establishment of sex determination in a multitude of organisms. The discovery of the master sex-determining gene SRY in 1990 was pivotal for the understanding of how testis development is initiated in mammals. With this discovery, an entire family of SOX factors were uncovered that play crucial roles in cell fate decisions during development. The importance of SOX genes in human reproductive development is evident from the various disorders of sex development (DSD) upon loss or overexpression of SOX gene function. Here, we review the roles that SOX genes play in gonad development and their involvement in DSD. We start with an overview of sex determination and differentiation, DSDs, and the SOX gene family and function. We then provide detailed information and discussion on SOX genes that have been implicated in DSDs, both at the gene and regulatory level. These include SRY, SOX9, SOX3, SOX8, and SOX10. This review provides insights on the crucial balance of SOX gene expression levels needed for gonad development and maintenance and how changes in these levels can lead to DSDs.
Topics: Animals; Humans; Male; Disorders of Sex Development; Sex Determination Processes; Sex Differentiation; SOX9 Transcription Factor; SOXE Transcription Factors; Testis
PubMed: 35760052
DOI: 10.1159/000524453 -
European Journal of Medical Genetics Sep 2019Human infertility is a healthcare problem that has a worldwide impact. Genetic causes of human infertility include chromosomal aneuploidies and rearrangements and... (Review)
Review
Human infertility is a healthcare problem that has a worldwide impact. Genetic causes of human infertility include chromosomal aneuploidies and rearrangements and single-gene defects. The sex chromosomes (X and Y) are critical players in human fertility since they contain several genes essential for sex determination and reproductive traits for both men and women. This paper provides a review of the most common sex chromosomes-linked single-gene disorders involved in human infertility and their corresponding phenotypes. In addition to the Y-linked SRY gene, which mutations may cause XY gonadal dysgenesis and sex reversal, the deletions of genes present in AZF regions of the Y chromosome (DAZ, RBMY, DBY and USP9Y genes) are implicated in varying degrees of spermatogenic dysfunction. Furthermore, a list of X-linked genes (KAL1, NR0B1, AR, TEX11, FMR1, PGRMC1, BMP15 and POF1 and 2 regions genes (XPNPEP2, POF1B, DACH2, CHM and DIAPH2)) were reported to have critical roles in pubertal and reproductive deficiencies in humans, affecting only men, only women or both sexes. Mutations in these genes may be transmitted to the offspring by a dominant or a recessive inheritance.
Topics: Disorders of Sex Development; Female; Genetic Diseases, X-Linked; Genetic Diseases, Y-Linked; Humans; Infertility; Male
PubMed: 31402110
DOI: 10.1016/j.ejmg.2018.10.012 -
American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Women and Birth : Journal of the... Feb 2023The birth of a baby with ambiguous genitalia is rare and usually unexpected. Parents often receive inconsistent language from health-professionals after the birth....
PROBLEM AND BACKGROUND
The birth of a baby with ambiguous genitalia is rare and usually unexpected. Parents often receive inconsistent language from health-professionals after the birth. Initial interaction with the birth team has long-term consequences for families with babies born with ambiguous genitalia.
AIM
Understand the current practices on the day of birth and explore knowledge gaps for midwives regarding babies born with ambiguous genitalia. Develop educational content that can enable midwives to respond appropriately when the sex of a baby is unclear.
METHODS
This study included two phases, utilising qualitative descriptive research design with semi-structured interviews to understand the experiences of midwives caring for babies with ambiguous genitalia and their families. The findings informed the development a midwifery educational resource using these qualitative findings.
FINDINGS
Our analysis of 14 interviews with Australian midwives identified that they had no formal education to support families with a baby with ambiguous genitalia. Emotional support, advocacy and medical information translation were areas midwives perceived as essential skills to support these families.
DISCUSSION
Midwives provide a unique role in parental birth experiences. Themes that arose emphasised their psychosocial support role but lacked formal education and guidance on this topic. Midwives had learnt from the media about babies born with ambiguous genitalia and wanted evidence-based education to support parents. Midwife education focusing on both psychosocial and clinical care for parents and their baby with ambiguous genitalia is crucial.
CONCLUSION
Midwives can play a pivotal role in supporting parents with a baby with ambiguous genitalia. Themes from this qualitative study informed the development of a midwifery education digital resource.
Topics: Pregnancy; Infant; Female; Humans; Midwifery; Australia; Parturition; Attitude of Health Personnel; Qualitative Research; Disorders of Sex Development; Nurse Midwives
PubMed: 35697608
DOI: 10.1016/j.wombi.2022.05.007 -
Frontiers in Endocrinology 2024Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent... (Review)
Review
Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent only a small number of these diseases. Due to the rarity of non-CAH 46,XX DSD, data on this sex chromosomal aberration were confined to case reports or case series with small numbers of patients. As the literature is still relatively sparse, medical data on the long-term effects of these pathologies remain scarce. In this review, we aim to provide an overview of current data on the long-term follow-up of patients with non-CAH 46,XX DSD, by covering the following topics: quality of life, gender identity, fertility and sexuality, global health, bone and cardiometabolic effects, cancer risk, and mortality. As non-CAH 46,XX DSD is a very rare condition, we have no accurate data on adult QoL assessment for these patients. Various factors may contribute to a legitimate questioning about their gender identity, which may differ from their sex assigned at birth. A significant proportion of gender dysphoria has been reported in various series of 46,XX DSD patients. However, it is difficult to give an accurate prevalence of gender dysphoria and gender reassignment in non-CAH 46,XX DSD because of the rarity of the data. Whatever the aetiology of non-CAH 46,XX DSD, fertility seems to be impaired. On the other hand, sexuality appears preserved in 46,XX men, whereas it is impaired in women with MRKH syndrome before treatment. Although there is still a paucity of data on general health, bone and cardiometabolic effects, and mortality, it would appear that the 46,XX DSD condition is less severely affected than other DSD conditions. Further structured and continued multi-center follow-up is needed to provide more information on the long-term outcome of this very rare non-CAH 46,XX DSD condition.
Topics: Female; Humans; Male; 46, XX Disorders of Sex Development; Adrenal Hyperplasia, Congenital; Disorders of Sex Development; Fertility; Gender Identity; Quality of Life
PubMed: 38752171
DOI: 10.3389/fendo.2024.1372887 -
Frontiers in Endocrinology 2023Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia that can manifest with skeletal malformations, ambiguous genitalia, and... (Review)
Review
Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia that can manifest with skeletal malformations, ambiguous genitalia, and menstrual disorders caused by cytochrome P450 oxidoreductase (POR) mutations affecting electron transfer to all microsomal cytochrome P450 and some non-P450 enzymes involved in cholesterol, sterol, and drug metabolism. With the advancement of molecular biology and medical genetics, increasing numbers of PORD cases were reported, and the clinical spectrum of PORD was extended with studies on underlying mechanisms of phenotype-genotype correlations and optimum treatment. However, diagnostic challenges and management dilemma still exists because of unawareness of the condition, the overlapping manifestations with other disorders, and no clear guidelines for treatment. Delayed diagnosis and management may result in improper sex assignment, loss of reproductive capacity because of surgical removal of ruptured ovarian macro-cysts, and life-threatening conditions such as airway obstruction and adrenal crisis. The clinical outcomes and prognosis, which are influenced by specific POR mutations, the presence of additional genetic or environmental factors, and management, include early death due to developmental malformations or adrenal crisis, bilateral oophorectomies after spontaneous rupture of ovarian macro-cysts, genital ambiguity, abnormal pubertal development, and nearly normal phenotype with successful pregnancy outcomes by assisted reproduction. Thus, timely diagnosis including prenatal diagnosis with invasive and non-invasive techniques and appropriate management is essential to improve patients' outcomes. However, even in cases with conclusive diagnosis, comprehensive assessment is needed to avoid severe complications, such as chromosomal test to help sex assignment and evaluation of adrenal function to detect partial adrenal insufficiency. In recent years, it has been noted that proper hormone replacement therapy can lead to decrease or resolve of ovarian macro-cysts, and healthy babies can be delivered by in vitro fertilization and frozen embryo transfer following adequate control of multiple hormonal imbalances. Treatment may be complicated with adverse effects on drug metabolism caused by POR mutations. Unique challenges occur in female PORD patients such as ovarian macro-cysts prone to spontaneous rupture, masculinized genitalia without progression after birth, more frequently affected pubertal development, and impaired fertility. Thus, this review focuses only on 46, XX PORD patients to summarize the potential molecular pathogenesis, differential diagnosis of classic and non-classic PORD, and tailoring therapy to maintain health, avoid severe complications, and promote fertility.
Topics: Female; Pregnancy; Humans; Adrenal Hyperplasia, Congenital; Antley-Bixler Syndrome Phenotype; Rupture, Spontaneous; Karyotype; Disorders of Sex Development; Cysts
PubMed: 37635957
DOI: 10.3389/fendo.2023.1226387