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Canadian Medical Association Journal Nov 1950
Topics: Disorders of Sex Development
PubMed: 14778107
DOI: No ID Found -
Hormone Research in Paediatrics 2023Disorders/differences of sex development (DSD) comprise a heterogeneous group of inborn conditions where the individual's sex chromosomes, gonads, and/or anatomical sex... (Review)
Review
BACKGROUND
Disorders/differences of sex development (DSD) comprise a heterogeneous group of inborn conditions where the individual's sex chromosomes, gonads, and/or anatomical sex are discordant. Since the Chicago Consensus Conference in 2005, multidisciplinary care has been implemented in specialised paediatric tertiary care centres and clinical practice has substantially changed towards a more holistic approach.
SUMMARY
Psychological support has become a key factor in the management of DSD. After paediatric care, one of the main challenges is the transition of patients to expert care in adulthood. Patients frequently experience difficulties in accessing specialised medical care in adulthood, resulting in loss to follow-up affecting the patients' physical and psychological health as well as quality of life. Clinical features and long-term outcomes are highly variable in most DSD conditions. Although medical care has improved, morbidity and mortality are increased in all conditions. A particular challenge in the care of DSD patients in adulthood is optimisation of fertility potential. Ideally, this is addressed already in adolescence and requires close interaction of not only paediatricians and adult endocrinologists but also urologists, andrologists or gynaecologists, and psychologists.
KEY MESSAGES
This review addresses issues relating to transition of DSD care from the paediatric to adult care as well as health-related challenges in adulthood in DSD.
Topics: Adolescent; Humans; Adult; Child; Disorders of Sex Development; Quality of Life; Transition to Adult Care; Fertility; Mental Health
PubMed: 36473446
DOI: 10.1159/000527433 -
International Journal of Molecular... Nov 2019Sex development is a complex process involving many genes and hormones. Defects in this process lead to Differences of Sex Development (DSD), a group of heterogeneous... (Review)
Review
Sex development is a complex process involving many genes and hormones. Defects in this process lead to Differences of Sex Development (DSD), a group of heterogeneous conditions not as rare as previously thought. Part of the obstacles in proper management of these patients is due to an incomplete understanding of the genetics programs and molecular pathways involved in sex development and DSD. Several challenges delay progress and the lack of a proper model system for the single patient severely hinders advances in understanding these diseases. The revolutionary techniques of cellular reprogramming and guided in vitro differentiation allow us now to exploit the versatility of induced pluripotent stem cells to create alternatives models for DSD, ideally on a patient-specific personalized basis.
Topics: Animals; Cellular Reprogramming Techniques; Disorders of Sex Development; Gonads; Humans; Induced Pluripotent Stem Cells; Patient-Specific Modeling; Primary Cell Culture
PubMed: 31690065
DOI: 10.3390/ijms20215495 -
Hormone Research in Paediatrics 2023DSD encompass a wide range of pathologies that impact gonad formation, development, and function in both 46,XX and 46,XY individuals. The majority of these conditions... (Review)
Review
BACKGROUND
DSD encompass a wide range of pathologies that impact gonad formation, development, and function in both 46,XX and 46,XY individuals. The majority of these conditions are considered to be monogenic, although the expression of the phenotype may be influenced by genetic modifiers. Although considered monogenic, establishing the genetic etiology in DSD has been difficult compared to other congenital disorders for a number of reasons including the absence of family cases for classical genetic association studies and the lack of evolutionary conservation of key genetic factors involved in gonad formation. In recent years, the widespread use of genomic sequencing technologies has resulted in multiple genes being identified and proposed as novel monogenic causes of 46,XX and/or 46,XY DSD.
SUMMARY
In this review, we will focus on the main genomic findings of recent years, which consists of new candidate genes or loci for DSD as well as new reproductive phenotypes associated with genes that are well established to cause DSD. For each gene or loci, we summarize the data that are currently available in favor of or against a role for these genes in DSD or the contribution of genomic variants within well-established genes to a new reproductive phenotype.
KEY MESSAGES
Based on this analysis, we propose a series of recommendations that should aid the interpretation of genomic data and ultimately help to improve the accuracy and yield genetic diagnosis of DSD.
Topics: Humans; Phenotype; Disorders of Sex Development
PubMed: 34963118
DOI: 10.1159/000521381 -
The Journal of Clinical Endocrinology... Mar 2011
Topics: Adrenal Hyperplasia, Congenital; Disorders of Sex Development; Female; Genitalia; Humans; Infant, Newborn; Male; Sex Reassignment Procedures; Terminology as Topic
PubMed: 21378218
DOI: 10.1210/jcem.96.3.zeg33a -
Frontiers in Endocrinology 2021Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and... (Review)
Review
Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.
Topics: Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Disorders of Sex Development; Humans; Sex Differentiation
PubMed: 34987475
DOI: 10.3389/fendo.2021.770782 -
Best Practice & Research. Clinical... Apr 2010Disorder of sex development (DSD) presents a unique challenge, both diagnostically and in terms of acute and longer-term management. These are relatively rare conditions... (Review)
Review
Disorder of sex development (DSD) presents a unique challenge, both diagnostically and in terms of acute and longer-term management. These are relatively rare conditions usually requiring a multidisciplinary approach from the outset and the involvement of a tertiary centre for assessment and management recommendations. This article describes the structure of the multidisciplinary team (MDT) at our centre, with contributions from key members of the team regarding their individual roles. The focus is on the newborn referred for assessment of ambiguous genitalia, rather than on individuals who present in the adolescent period or at other times, although the same MDT involvement is likely to be required. The approach to the initial assessment and management is discussed and the subsequent diagnosis and follow-up presented, with emphasis on the importance of careful transition and long-term support.
Topics: Adolescent; Adult; Child; Disorders of Sex Development; Endocrinology; Female; Holistic Health; Humans; Infant; Infant, Newborn; Male; Molecular Biology; Patient Care Team; Referral and Consultation; Urology
PubMed: 20541156
DOI: 10.1016/j.beem.2010.01.006 -
Sexual Development : Genetics,... 2018
Topics: Disorders of Sex Development; Humans; Sexual Development
PubMed: 29055947
DOI: 10.1159/000480746 -
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: Humans; 46, XX Disorders of Sex Development; Quality of Life; Female; Male; Adrenal Hyperplasia, Congenital; Gender Identity; Disorders of Sex Development; Fertility
PubMed: 38752171
DOI: 10.3389/fendo.2024.1372887 -
BMJ (Clinical Research Ed.) Dec 2001
Topics: Attitude of Health Personnel; Clitoris; Disorders of Sex Development; Evidence-Based Medicine; Female; Humans; Infant; Male; Truth Disclosure; Vagina
PubMed: 11731376
DOI: 10.1136/bmj.323.7324.1264