Genetic testing in inherited endocrine disorders: joint position paper of the European reference network on rare endocrine conditions (Endo-ERN)
Authors: Eggermann Thomas , Elbracht Miriam , Kurth Ingo , Juul Anders , Johannsen Trine Holm , Netchine Irène , Mastorakos George , Johannsson Gudmundur , Musholt Thomas J. , Zenker Martin , Prawitt Dirk , Pereira Alberto M. , Hiort Olaf ,   on behalf of the European Reference Network on Rare Endocrine Conditions (ENDO-ERN, Riedl Stefan , Rami-Merhar Birgit , Vila Greisa , Baumgartner-Parzner Sabina , Bonfig Walter , Heinrichs Claudine , Maiter Dominique , Gies Inge , Cools Martine , Casteels Kristina , Beckers Albert , Zacharieva Sabina , Iotova Violeta , Jukic Tomislav , Rahelic Dario , Neocleous Vassos , Phylactou Leonidas , Krsek Michal , Lebl Jan , Gravholt Claus , Juul Anders , Tillmann Vallo , Volke Vallo , Ebeling Tapani , Brue Thierry , Rodien Patrice , Bertherat Jérôme , Bernert Christine Poitou , Touraine Philippe , Chanson Philippe , Polak Michel , Tauber Maithe , Eggermann Thomas , Spranger Joachim , Fuhrer Dagmar , Danne Thomas , Hiort Olaf , Mohnike Klaus , Prawitt Dirk , Luster Markus , Reisch Nicole , Reincke Martin , Rohayem Julia , Fassnacht Martin , Tóth Miklós , Cassio Alessandra , Toni Sonia , Krausz Csilla , Piccini Barbara , Ferone Diego , Russo Gianni , Persani Luca , Colao Annamaria , Salerno Mariacarolina , Boscaro Marco , Scaroni Carla , Santini Ferruccio , Ceccarini Giovanni , Ghigo Ezio , Dzivite - Krisane Iveta , Rovite Vita , Janozola Lauma , Verkauskiene Rasa , Witsch Michael , Clark James , Romijn Johannes , Links Thera , Biermasz Nienke , Hannema Sabine , Havekes Bas , der Grinten Hedi Claahsen-van , Timmers Henri , Peeters Robin , Valk Gerlof , Stuart A. A. Verrijn , Haak Harm , Husebye Eystein , Bollerslev Jens , Jarzab Barbara , ‘Szypowska Agnieszka , Raposo João-Filipe , Craiu Dana , Piciu Doina , Kostalova Ludmila , Vojtková Jarmila , Battelino Tadej , Cardona-Hernandez Roque , Yeste Diego , Gaztambide Sonia , Nordenström Anna , Gittoes Neil , Cole Trevor , Crowne Elizabeth , Ahmed Faisal , Didi Mohammed , Korbonits Marta , Dattani Mehul , Clayton Peter , Davies Justin 
Published: June 2020

Background

With the development of molecular high-throughput assays (i.e. next generation sequencing), the knowledge on the contribution of genetic and epigenetic alterations to the etiology of inherited endocrine disorders has massively expanded. However, the rapid implementation of these new molecular tools in the diagnostic settings makes the interpretation of diagnostic data increasingly complex.

Main body

This joint paper of the ENDO-ERN members aims to overview chances, challenges, limitations and relevance of comprehensive genetic diagnostic testing in rare endocrine conditions in order to achieve an early molecular diagnosis. This early diagnosis of a genetically based endocrine disorder contributes to a precise management and helps the patients and their families in their self-determined planning of life. Furthermore, the identification of a causative (epi)genetic alteration allows an accurate prognosis of recurrence risks for family planning as the basis of genetic counselling. Asymptomatic carriers of pathogenic variants can be identified, and prenatal testing might be offered, where appropriate.

Conclusions

The decision on genetic testing in the diagnostic workup of endocrine disorders should be based on their appropriateness to reliably detect the disease-causing and –modifying mutation, their informational value, and cost-effectiveness. The future assessment of data from different omic approaches should be embedded in interdisciplinary discussions using all available clinical and molecular data.