GENETICS IN ENDOCRINOLOGY: Approaches to molecular genetic diagnosis in the management of differences/disorders of sex development (DSD): position paper of EU COST Action BM 1303 "DSDnet"

in European Journal of Endocrinology
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  • 1 L Audí, Department of Pediatrics and Pediatric Endocrinology Unit, Hospital Vall d´Hebron, Barcelona, 08035, Spain
  • | 2 S Ahmed, Developmental Endocrinology Research Group, University of Glasgow, Glasgow, G51 4TF, United Kingdom of Great Britain and Northern Ireland
  • | 3 N Krone, Academic Unit of Child Health, Department of Oncology and Metabolism, University of Sheffield, Sheffield, S10 2TG, United Kingdom of Great Britain and Northern Ireland
  • | 4 M Cools, Department of Paediatric Endocrinology, Universitair Ziekenhuis Gent, Gent, Belgium
  • | 5 K McElreavey, Human Developmental Genetics, Institut Pasteur, Paris, France
  • | 6 P Holterhus, Department of Pediatrics, University of Kiel, Kiel, Germany
  • | 7 A Greenfield, Mammalian Genetics Unit, Medical Research Council, Harwell Institute, Oxfordshire, United Kingdom of Great Britain and Northern Ireland
  • | 8 A Bashamboo, Human Developmental Genetics, Institut Pasteur, Paris, France
  • | 9 O Hiort, Division of Paediatric Endocrinology and Diabetes. Department of Paediatric and Adolescent Medicine, Universitat zu Lubeck Sektion Medizin, Lubeck, Germany
  • | 10 S Wudy, Steroid Research and Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus-Liebig-University, Giessen, Germany
  • | 11 R McGowan, Department of Clinical Genetics, Queen Elizabeth University Hospital Campus, Glasgow, United Kingdom of Great Britain and Northern Ireland

Correspondence: Laura Audí, Email:
Open access

The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 "DSDnet" was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV), or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case.


     European Society of Endocrinology