Robert Meyer1, Lukas Soellner1, Matthias Begemann1, Severin Dicks1, György Fekete2, Nils Rahner3, Klaus Zerres1, Miriam Elbracht1, Thomas Eggermann4. 1. Institute of Human Genetics, University Hospital, Technical University Aachen (Rheinisch-Westfälische Technische Hochschule), Aachen, Germany. 2. Second Department of Pediatrics, Semmelweis University, Budapest, Hungary. 3. University Clinic Düsseldorf, Institute of Human Genetics, Düsseldorf, Germany. 4. Institute of Human Genetics, University Hospital, Technical University Aachen (Rheinisch-Westfälische Technische Hochschule), Aachen, Germany. Electronic address: teggermann@ukaachen.de.
Abstract
OBJECTIVE: To investigate the contribution of differential diagnoses to the mutation spectrum of patients referred for Silver-Russell syndrome (SRS) testing. STUDY DESIGN: Forty-seven patients referred for molecular testing for SRS were examined after exclusion of one of the SRS-associated alterations. After clinical classification, a targeted next generation sequencing approach comprising 25 genes associated with other diagnoses or postulated as SRS candidate genes was performed. RESULTS: By applying the Netchine-Harbinson clinical scoring system, indication for molecular testing for SRS was confirmed in 15 out of 47 patients. In 4 out of these 15 patients, disease-causing variants were found in genes associated with other diagnoses. These patients carried mutations associated with Bloom syndrome, Mulibrey nanism, KBG syndrome, or IGF1R-associated short stature. We could not detect any pathogenic mutation in patients with a negative clinical score. CONCLUSIONS: Some of the differential diagnoses detected in the cohort presented here have a major impact on clinical management. Therefore, we emphasize that the molecular defects associated with these clinical pictures should be excluded before the clinical diagnosis "SRS" is made. Finally, we could show that a broad molecular approach including the differential diagnoses of SRS increases the detection rate.
OBJECTIVE: To investigate the contribution of differential diagnoses to the mutation spectrum of patients referred for Silver-Russell syndrome (SRS) testing. STUDY DESIGN: Forty-seven patients referred for molecular testing for SRS were examined after exclusion of one of the SRS-associated alterations. After clinical classification, a targeted next generation sequencing approach comprising 25 genes associated with other diagnoses or postulated as SRS candidate genes was performed. RESULTS: By applying the Netchine-Harbinson clinical scoring system, indication for molecular testing for SRS was confirmed in 15 out of 47 patients. In 4 out of these 15 patients, disease-causing variants were found in genes associated with other diagnoses. These patients carried mutations associated with Bloom syndrome, Mulibrey nanism, KBG syndrome, or IGF1R-associated short stature. We could not detect any pathogenic mutation in patients with a negative clinical score. CONCLUSIONS: Some of the differential diagnoses detected in the cohort presented here have a major impact on clinical management. Therefore, we emphasize that the molecular defects associated with these clinical pictures should be excluded before the clinical diagnosis "SRS" is made. Finally, we could show that a broad molecular approach including the differential diagnoses of SRS increases the detection rate.
Authors: Helen L Storr; Sumana Chatterjee; Louise A Metherell; Corinne Foley; Ron G Rosenfeld; Philippe F Backeljauw; Andrew Dauber; Martin O Savage; Vivian Hwa Journal: Endocr Rev Date: 2019-04-01 Impact factor: 19.871
Authors: Danielle Christine Maria van der Kaay; Anne Rochtus; Gerhard Binder; Ingo Kurth; Dirk Prawitt; Irène Netchine; Gudmundur Johannsson; Anita C S Hokken-Koelega; Miriam Elbracht; Thomas Eggermann Journal: Endocr Connect Date: 2022-10-10 Impact factor: 3.221