scholarly journals Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development

2020 ◽  
Vol 57 (9) ◽  
pp. 581-589
Author(s):  
Yolande van Bever ◽  
Hennie T Brüggenwirth ◽  
Katja P Wolffenbuttel ◽  
Arianne B Dessens ◽  
Irene A L Groenenberg ◽  
...  
Keyword(s):  
Molecular Diagnostics ◽  
Network Formation ◽  
Quality Care ◽  
Daily Practice ◽  
Clinical Situation ◽  
Reference Network ◽  
International Consensus ◽  
Sex Development ◽  
Limited Experience ◽  
Differences Of Sex Development

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. These points are of interest to physicians working in DSD (expert) centres and to professionals who come across persons with a DSD but have no (or limited) experience in this area. The Dutch-Flemish guideline is based on internationally accepted principles. Recent initiatives striving for uniform high-quality care across Europe, and beyond, such as the completed COST action 1303 and the European Reference Network for rare endocrine conditions (EndoERN), have generated several excellent papers covering nearly all aspects of DSD. The Dutch-Flemish guideline follows these international consensus papers and covers a number of other topics relevant to daily practice. For instance, although next-generation sequencing (NGS)-based molecular diagnostics are becoming the gold standard for genetic evaluation, it can be difficult to prove variant causality or relate the genotype to the clinical presentation. Network formation and centralisation are essential to promote functional studies that assess the effects of genetic variants and to the correct histological assessment of gonadal material from DSD patients, as well as allowing for maximisation of expertise and possible cost reductions. 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. Referral to ultrasound sonographers and obstetricians who are part of a DSD team is increasingly important here. 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. Their thoughtful communication to patients, carers and colleagues, and the accessibility of protocols for first-line management and efficient referral are essential. Careful communication in the prenatal to neonatal period and the adolescent to adult transition are equally important and relatively under-reported in the literature. 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.

scholarly journals Peptide hormone analysis in diagnosis and treatment of Differences of Sex Development: joint position paper of EU COST Action ‘DSDnet’ and European Reference Network on Rare Endocrine Conditions

2020 ◽  
Vol 182 (6) ◽  
pp. P1-P15
Author(s):  
T H Johannsen ◽  
A-M Andersson ◽  
S F Ahmed ◽  
Y B de Rijke ◽  
R F Greaves ◽  
...  
Keyword(s):  
Peptide Hormone ◽  
Position Paper ◽  
Inhibin B ◽  
Diagnosis And Treatment ◽  
Reference Network ◽  
Cost Action ◽  
Sex Development ◽  
European Reference Network ◽  
Differences Of Sex Development ◽  
Hormone Analysis

Differences of Sex Development (DSD) comprise a variety of congenital conditions characterized by atypical chromosomal, gonadal, or anatomical sex. Diagnosis and monitoring of treatment of patients suspected of DSD conditions include clinical examination, measurement of peptide and steroid hormones, and genetic analysis. This position paper on peptide hormone analyses in the diagnosis and control of patients with DSD was jointly prepared by specialists in the field of DSD and/or peptide hormone analysis from the European Cooperation in Science and Technology (COST) Action DSDnet (BM1303) and the European Reference Network on rare Endocrine Conditions (Endo-ERN). The goal of this position paper on peptide hormone analysis was to establish laboratory guidelines that may contribute to improve optimal diagnosis and treatment control of DSD. The essential peptide hormones used in the management of patients with DSD conditions are follicle-stimulating hormone, luteinising hormone, anti-Müllerian hormone, and Inhibin B. In this context, the following position statements have been proposed: serum and plasma are the preferred matrices; the peptide hormones can all be measured by immunoassay, while use of LC-MS/MS technology has yet to be implemented in a diagnostic setting; sex- and age-related reference values are mandatory in the evaluation of these hormones; and except for Inhibin B, external quality assurance programs are widely available.

Recalled and current gender role behavior, gender identity and sexual orientation in adults with Disorders/Differences of Sex Development

2016 ◽  
Vol 86 ◽  
pp. 8-20 ◽  
Author(s):  
Nina Callens ◽  
Maaike Van Kuyk ◽  
Jet H. van Kuppenveld ◽  
Stenvert L.S. Drop ◽  
Peggy T. Cohen-Kettenis ◽  
...  
Keyword(s):  
Sexual Orientation ◽  
Gender Identity ◽  
Gender Role ◽  
Role Behavior ◽  
Sex Development ◽  
Gender Role Behavior ◽  
Differences Of Sex Development

scholarly journals Assembling the jigsaw puzzle: CBX2 isoform 2 and its targets in disorders/differences of sex development

2018 ◽  
Vol 6 (5) ◽  
pp. 785-795 ◽  
Author(s):  
Patrick Sproll ◽  
Wassim Eid ◽  
Camila R. Gomes ◽  
Berenice B. Mendonca ◽  
Nathalia L. Gomes ◽  
...  
Keyword(s):  
Jigsaw Puzzle ◽  
Sex Development ◽  
Differences Of Sex Development

The Interconnected Histories of Endocrinology and Eligibility in Women’s Sport

2018 ◽  
Vol 90 (4) ◽  
pp. 213-220 ◽  
Author(s):  
Alan D. Rogol ◽  
Lindsay Parks Pieper
Keyword(s):  
Female Athletes ◽  
International Association ◽  
Historical Context ◽  
International Olympic Committee ◽  
Elite Sport ◽  
Women's Sport ◽  
Current Effort ◽  
Sex Development ◽  
Differences Of Sex Development

This report illustrates the links between history, sport, endocrinology, and genetics to show the ways in which historical context is key to understanding the current conversations and controversies about who may compete in the female category in elite sport. The International Association of Athletics Federations (IAAF) introduced hyperandrogenemia regulations for women’s competitions in 2011, followed by the International Olympic Committee (IOC) for the 2012 Olympics. The policies concern female athletes who naturally produce higher-than-average levels of testosterone and want to compete in the women’s category. Hyperandrogenemia guidelines are the current effort in a long series of attempts to determine women’s eligibility scientifically. Scientific endeavors to control who may participate as a woman illustrate the impossibility of neatly classifying competitors by sex and discriminate against women with differences of sex development (also called intersex by some).

scholarly journals Pediatric Urologists of Canada (PUC) 2021 position statement: Differences of sex development (AKA disorders of sex development)

2021 ◽  
Vol 15 (12) ◽  
Author(s):  
Rodrigo L.P. Romao ◽  
Luis H. Braga ◽  
Melise Keays ◽  
Peter Metcalfe ◽  
Karen Psooy ◽  
...  
Keyword(s):  
Disorders Of Sex Development ◽  
Position Statement ◽  
Sex Development ◽  
Differences Of Sex Development

scholarly journals Testis formation in XX individuals resulting from novel pathogenic variants in Wilms’ tumor 1 (WT1) gene

2020 ◽  
Vol 117 (24) ◽  
pp. 13680-13688 ◽  
Author(s):  
Caroline Eozenou ◽  
Nitzan Gonen ◽  
Maria Sol Touzon ◽  
Anne Jorgensen ◽  
Svetlana A. Yatsenko ◽  
...  
Keyword(s):  
De Novo ◽  
Wilms Tumor ◽  
Testicular Tissue ◽  
Sex Development ◽  
Pathogenic Variants ◽  
Differences Of Sex Development ◽  
Wilms Tumor 1 ◽  
Specific Pathway ◽  
Wt1 Protein ◽  
Antagonistic Interactions

Sex determination in mammals is governed by antagonistic interactions of two genetic pathways, imbalance in which may lead to disorders/differences of sex development (DSD) in human. Among 46,XX individuals with testicular DSD (TDSD) or ovotesticular DSD (OTDSD), testicular tissue is present in the gonad. Although the testis-determining geneSRYis present in many cases, the etiology is unknown in mostSRY-negative patients. We performed exome sequencing on 78 individuals with 46,XX TDSD/OTDSD of unknown genetic etiology and identified seven (8.97%) with heterozygous variants affecting the fourth zinc finger (ZF4) of Wilms’ tumor 1 (WT1) (p.Ser478Thrfs*17, p.Pro481Leufs*15, p.Lys491Glu, p.Arg495Gln [x3], p.Arg495Gly). The variants were de novo in six families (P= 4.4 × 10−6), and the incidence of WT1 variants in 46,XX DSD is enriched compared to control populations (P< 1.8 × 10−4). The introduction of ZF4 mutants into a human granulosa cell line resulted in up-regulation of endogenous Sertoli cell transcripts andWt1Arg495Gly/Arg495GlyXX mice display masculinization of the fetal gonads. The phenotype could be explained by the ability of the mutated proteins to physically interact with and sequester a key pro-ovary factor β-CATENIN, which may lead to up-regulation of testis-specific pathway. Our data show that unlike previous association of WT1 and 46,XY DSD, ZF4 variants of WT1 are a relatively common cause of 46,XX TDSD/OTDSD. This expands the spectrum of phenotypes associated with WT1 variants and shows that the WT1 protein affecting ZF4 can function as a protestis factor in an XX chromosomal context.

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