S Fuchs1,2, G Gat-Yablonski1,3,4, B Shtaif3,4, L Lazar1,4, M Phillip1,3,4, Y Lebenthal5,6. 1. The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, 14 Kaplan Street, 49202, Petah Tikva, Israel. 2. Department of Molecular Genetics, Weizmann Institute of Science, 76100, Rehovot, Israel. 3. Felsenstein Medical Research Center, 49100, Petah Tikva, Israel. 4. Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel. 5. The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, 14 Kaplan Street, 49202, Petah Tikva, Israel. yael_lebenthal@walla.co.il. 6. Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel. yael_lebenthal@walla.co.il.
Abstract
CONTEXT: Noonan syndrome (NS) is characterized by short stature and elevated risk of lymphedema. The mechanism underlying lymphedema may be mediated by vascular endothelial growth factors (VEGFs). OBJECTIVE: To assess the effect of growth hormone (GH) treatment on plasma insulin-like growth factor (IGF)-1, VEGF-A and VEGF-C levels in patients with NS as compared to short GH-sufficient children. DESIGN: Retrospective, comparative. SETTING: Endocrinology department of a tertiary pediatric medical center. PATIENTS AND METHODS: Plasma IGF-1, VEGF-A and VEGF-C levels were measured before and during GH treatment in 6 patients with NS and 18 age-matched short subjects (Turner, idiopathic short stature and small for gestational age). MAIN OUTCOME MEASURES: Changes in plasma VEGF and IGF-1 levels. RESULTS: Baseline IGF-1 SDS levels were slightly lower in NS patients compared with controls; IGF-1 response to GH therapy was markedly lower in NS patients compared with controls (p = 0.017). Mean baseline VEGF-A levels were similar in NS patients and controls whilst mean baseline VEGF-C levels were significantly lower in the NS group as compared with controls (p = 0.022). Plasma VEGF-A and VEGF-C levels did not significantly change during GH treatment in the study cohort. No correlation was found between VEGF-C levels and levels of IGF-1, VEGF-A and auxological parameters, either before or during GH administration. CONCLUSION: Children with NS have a distinct growth factor profile including low basal VEGF-C and flattened IGF-1 response to GH. Further studies are needed to confirm our findings and to elucidate the interaction between VEGF-C levels and lymphedema.
CONTEXT: Noonan syndrome (NS) is characterized by short stature and elevated risk of lymphedema. The mechanism underlying lymphedema may be mediated by vascular endothelial growth factors (VEGFs). OBJECTIVE: To assess the effect of growth hormone (GH) treatment on plasma insulin-like growth factor (IGF)-1, VEGF-A and VEGF-C levels in patients with NS as compared to short GH-sufficient children. DESIGN: Retrospective, comparative. SETTING: Endocrinology department of a tertiary pediatric medical center. PATIENTS AND METHODS: Plasma IGF-1, VEGF-A and VEGF-C levels were measured before and during GH treatment in 6 patients with NS and 18 age-matched short subjects (Turner, idiopathic short stature and small for gestational age). MAIN OUTCOME MEASURES: Changes in plasma VEGF and IGF-1 levels. RESULTS: Baseline IGF-1SDS levels were slightly lower in NSpatients compared with controls; IGF-1 response to GH therapy was markedly lower in NSpatients compared with controls (p = 0.017). Mean baseline VEGF-A levels were similar in NSpatients and controls whilst mean baseline VEGF-C levels were significantly lower in the NS group as compared with controls (p = 0.022). Plasma VEGF-A and VEGF-C levels did not significantly change during GH treatment in the study cohort. No correlation was found between VEGF-C levels and levels of IGF-1, VEGF-A and auxological parameters, either before or during GH administration. CONCLUSION:Children with NS have a distinct growth factor profile including low basal VEGF-C and flattened IGF-1 response to GH. Further studies are needed to confirm our findings and to elucidate the interaction between VEGF-C levels and lymphedema.
Authors: Audrey De Rocca Serra-Nédélec; Thomas Edouard; Karine Tréguer; Mylène Tajan; Toshiyuki Araki; Marie Dance; Marianne Mus; Alexandra Montagner; Maïté Tauber; Jean-Pierre Salles; Philippe Valet; Benjamin G Neel; Patrick Raynal; Armelle Yart Journal: Proc Natl Acad Sci U S A Date: 2012-02-27 Impact factor: 11.205
Authors: Alicia A Romano; Ken Dana; Bert Bakker; D Aaron Davis; Joanne Julius Hunold; Joan Jacobs; Barbara Lippe Journal: J Clin Endocrinol Metab Date: 2009-04-28 Impact factor: 5.958
Authors: Suzanne Schubbert; Martin Zenker; Sara L Rowe; Silke Böll; Cornelia Klein; Gideon Bollag; Ineke van der Burgt; Luciana Musante; Vera Kalscheuer; Lars-Erik Wehner; Hoa Nguyen; Brian West; Kam Y J Zhang; Erik Sistermans; Anita Rauch; Charlotte M Niemeyer; Kevin Shannon; Christian P Kratz Journal: Nat Genet Date: 2006-02-12 Impact factor: 38.330