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Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development
  1. Yolande van Bever1,
  2. Hennie T Brüggenwirth1,
  3. Katja P Wolffenbuttel2,
  4. Arianne B Dessens3,
  5. Irene A L Groenenberg4,
  6. Maarten F C M Knapen4,
  7. Elfride De Baere5,
  8. Martine Cools6,
  9. Conny M A van Ravenswaaij-Arts7,
  10. Birgit Sikkema-Raddatz7,
  11. Hedi Claahsen-van der Grinten8,
  12. Marlies Kempers9,
  13. Tuula Rinne9,
  14. Remko Hersmus10,
  15. Leendert Looijenga10,11,
  16. Sabine E Hannema12,13
  1. 1 Department of Clinical Genetics and DSD Expert Center Erasmus Medical Center, Erasmus Medical Center, Rotterdam, The Netherlands
  2. 2 Department of Pediatric Urology and DSD Expert Center Erasmus Medical Center, Erasmus Medical Center, Rotterdam, The Netherlands
  3. 3 Department of Child and Adolescent Psychiatry and DSD Expert Center Erasmus Medical Center, Erasmus Medical Center, Rotterdam, The Netherlands
  4. 4 Department of Obstetrics and Prenatal Medicine and DSD Expert Center Erasmus Medical Center, Erasmus Medical Centre, Rotterdam, The Netherlands
  5. 5 Center for Medical Genetics, University Hospital Ghent Center Medical Genetics, Ghent, Belgium
  6. 6 Department of Internal Medicine and Paediatrics and Department of Pediatric Endocrinology, University Hospital Ghent, Ghent, Belgium
  7. 7 Department of Genetics and DSD team, University Medical Center Groningen, Groningen, The Netherlands
  8. 8 Department of Pediatric Endocrinology and DSD Expert Center Radboud UMC, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands
  9. 9 Department of Clinical genetics and DSD Expert Center Radboud UMC, Radboud University Medical Center, Nijmegen, The Netherlands
  10. 10 Department of Pathology, DSD Expert Center ErasmusMC, Erasmus MC-University Medical Centre, Rotterdam, The Netherlands
  11. 11 Department of Pathology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
  12. 12 Department of Pediatric Endocrinology and DSD Expert Center ErasmusMC, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
  13. 13 Department of Pediatrics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  1. Correspondence to Dr Yolande van Bever, Department of Clinical Genetics and DSD-Expert Center Erasmus Medical Center, Erasmus Medical Center Department of Clinical Genetics, 3015 GD Rotterdam, Dr Molewaterplein 40, The Netherlands; y.vanbever{at}erasmusmc.nl

Abstract

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.

  • DSD
  • NGS
  • guideline
  • diagnostic
  • prenatal
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This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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Footnotes

  • Twitter @elfridedebaere

  • Contributors Design, conceptualisation, submission and overall responsibility: YvB. Clinical and psychosocial information collection : YvB, KPW, ABD, MC, CvR-A, HC-vdG, MK, SEH. Genetic information collection: YvB, HTB, EDB, CvR-A, MK, TR. Prenatal information collection: YvB, ABD, IALG, MFCMK, MC, HC-vdG. Pathological aspects: MC, RH, LL. Writing the manuscript: YvB, HTB, EDB, MC, HC-vdG, SEH. Critical review: HTB, KPW, ABD, IALG, MFCMK, EDB, MC, CvR-A, HC-vdG, MK, LL, MC.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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