Comprehensive genetic testing approaches as the basis for personalized management of growth disturbances: current status and perspectives

Endocrine Connections, vol. 11

Abstract

The implementation of high-throughput and deep sequencing methods in routine genetic diagnostics has significantly improved the diagnostic yield in patient cohorts with growth disturbances and becomes increasingly important as the prerequisite of personalized medicine. They provide considerable chances to identify even rare and unexpected situations; nevertheless, we must be aware of their limitations. A simple genetic test in the beginning of a testing cascade might also help to identify the genetic cause of specific growth disorders. However, the clinical picture of genetically caused growth disturbance phenotypes can vary widely, and there is a broad clinical overlap between different growth disturbance disorders. As a consequence, the clinical diagnosis and therewith connected the decision on the appropriate genetic test is often a challenge. In fact, the clinician asking for genetic testing has to weigh different aspects in this decision process, including appropriateness (single gene test, stepwise procedure, comprehensive testing), turnaround time as the basis for rapid intervention, and economic considerations. Therefore, a frequent question in that context is 'what to test when'. In this review, we aim to review genetic testing strategies and their strengths and limitations and to raise awareness for the future implementation of interdisciplinary genome medicine in diagnoses, treatment, and counselling of growth disturbances.

Authors 10

1. Daniëlle C M van der Kaay

   Erasmus MC

   Affiliation as printed

   Erasmus University Medical Center, Department of Pediatrics, Subdivision of Endocrinology, Rotterdam, Netherlands

2. Anne Maria Rochtus

   Universitair Ziekenhuis Leuven

   Affiliation as printed

   Department of Pediatric Endocrinology, University Hospitals Leuven, Leuven, Belgium

3. Gerhard Binder

   University Children's Hospital Tübingen · University of Tübingen

   Affiliation as printed

   University Children’s Hospital, Pediatric Endocrinology, University of Tübingen, Tübingen, Germany

4. Ingo Kurth Aachen Institute of Human Genetics Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany

5. Dirk Prawitt

   University Medical Center of the Johannes Gutenberg University Mainz

   Affiliation as printed

   Center for Paediatrics and Adolescent Medicine, University Medical Center, Mainz, Germany

6. Irène Netchine

   Inserm · Sorbonne Université · Assistance Publique – Hôpitaux de Paris · Centre de Recherche Saint-Antoine

   Affiliation as printed

   Sorbonne Université, Centre de Recherche Saint-Antoine, INSERM, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France

7. Gudmundur Johannsson

   Sahlgrenska University Hospital · University of Gothenburg

   Affiliation as printed

   Department of Endocrinology at Sahlgrenska University Hospital, Gothenburg, Sweden

   Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8. Anita C. S. Hokken‐Koelega

   Erasmus MC

   Affiliation as printed

   Erasmus University Medical Center, Department of Pediatrics, Subdivision of Endocrinology, Rotterdam, Netherlands

9. Miriam Elbracht Aachen Institute of Human Genetics Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany

10. Thomas Eggermann Aachen Institute of Human Genetics Medical Faculty

    RWTH Aachen University

    Affiliation as printed

    Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany