Catie Cessans1, Virginie Ehlinger2, Catherine Arnaud3, Armelle Yart4, Yline Capri5, Pascal Barat6, Benoit Cammas6, Didier Lacombe7, Régis Coutant8, Albert David9, Sabine Baron10, Jacques Weill11, Bruno Leheup12, Marc Nicolino13, Jean-Pierre Salles14, Alain Verloes5, Maithé Tauber14, Hélène Cavé5, Thomas Edouard15. 1. EndocrineBone Diseases, and Genetics Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France. 2. UMR 1027 INSERMUniversity of Toulouse Paul Sabatier, Toulouse, France. 3. UMR 1027 INSERMUniversity of Toulouse Paul Sabatier, Toulouse, France Clinical Epidemiology UnitToulouse University Hospital, Toulouse, France. 4. INSERM UMR 1048Institute of Cardiovascular and Metabolic Diseases (I2MC), University of Toulouse Paul Sabatier, Toulouse, France. 5. Departments of GeneticsRobert-Debré University Hospital, APHP, Paris, France. 6. Pediatric Endocrinology DepartmentClinical investigation Centre (CIC 1401), Bordeaux University Hospital, Bordeaux, France. 7. Genetics DepartmentBordeaux University Hospital, EA4576, Bordeaux, France. 8. Pediatric Endocrinology DepartmentAngers University Hospital, Angers, France. 9. Genetics DepartmentNantes University Hospital, Nantes, France. 10. Pediatric Endocrine UnitNantes University Hospital, Nantes, France. 11. Pediatric Endocrine UnitLille University Hospital, Lille, France. 12. Pediatric and Genetics UnitNancy University Hospital, Vandoeuvre, France. 13. Pediatric Endocrinology DepartmentLyon University Pediatric Hospital, INSERM U.1060/UCBL/HCL, France. 14. EndocrineBone Diseases, and Genetics Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France INSERM UMR 1043Centre of Pathophysiology of Toulouse Purpan (CPTP), University of Toulouse Paul Sabatier, Toulouse, France. 15. EndocrineBone Diseases, and Genetics Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France INSERM UMR 1043Centre of Pathophysiology of Toulouse Purpan (CPTP), University of Toulouse Paul Sabatier, Toulouse, France edouard.t@chu-toulouse.fr.
Abstract
BACKGROUND: Growth patterns of patients with Noonan syndrome (NS) were established before the involved genes were identified. OBJECTIVE: The goal of this study was to compare growth parameters according to genotype in patients with NS. SUBJECTS AND METHODS: The study population included 420 patients (176 females and 244 males) harboring mutations in the PTPN11, SOS1, RAF1, or KRAS genes. NS-associated PTPN11 mutations (NS-PTPN11) and NS with multiple lentigines-associated PTPN11 mutations (NSML-PTPN11) were distinguished. Birth measures and height and body mass index (BMI) measures at 2, 5, 10 years, and adulthood were compared with the general population and between genotypes. RESULTS: Patients with NS were shorter at birth (mean birth length standard deviation score (SDS): -1.0 ± 1.4; P < 0.001) and throughout childhood than the healthy population, with height SDS being -2.1 ± 1.3 at 2 years, and -2.1 ± 1.2 at 5 and 10 years and adulthood (P < 0.001). At birth, patients with NS-PTPN11 were significantly shorter and thinner than patients with NSML-PTPN11, SOS1, or KRAS. Growth retardation was significantly less severe and less frequent at 2 years in patients with NSML-PTPN11 and SOS1 than in patients with NS-PTPN11 (P < 0.001 and P = 0.002 respectively). Patients with NS had lower BMI at 10 years (P < 0.001). No difference between genotypes was demonstrated. CONCLUSION: Determining the growth patterns of patients with NS according to genotype should better inform clinicians about the natural course of growth in NS so that they can optimize the follow-up and management of these patients.
BACKGROUND: Growth patterns of patients with Noonan syndrome (NS) were established before the involved genes were identified. OBJECTIVE: The goal of this study was to compare growth parameters according to genotype in patients with NS. SUBJECTS AND METHODS: The study population included 420 patients (176 females and 244 males) harboring mutations in the PTPN11, SOS1, RAF1, or KRAS genes. NS-associated PTPN11 mutations (NS-PTPN11) and NS with multiple lentigines-associated PTPN11 mutations (NSML-PTPN11) were distinguished. Birth measures and height and body mass index (BMI) measures at 2, 5, 10 years, and adulthood were compared with the general population and between genotypes. RESULTS:Patients with NS were shorter at birth (mean birth length standard deviation score (SDS): -1.0 ± 1.4; P < 0.001) and throughout childhood than the healthy population, with height SDS being -2.1 ± 1.3 at 2 years, and -2.1 ± 1.2 at 5 and 10 years and adulthood (P < 0.001). At birth, patients with NS-PTPN11 were significantly shorter and thinner than patients with NSML-PTPN11, SOS1, or KRAS. Growth retardation was significantly less severe and less frequent at 2 years in patients with NSML-PTPN11 and SOS1 than in patients with NS-PTPN11 (P < 0.001 and P = 0.002 respectively). Patients with NS had lower BMI at 10 years (P < 0.001). No difference between genotypes was demonstrated. CONCLUSION: Determining the growth patterns of patients with NS according to genotype should better inform clinicians about the natural course of growth in NS so that they can optimize the follow-up and management of these patients.
Authors: Granton A Jindal; Yogesh Goyal; Kei Yamaya; Alan S Futran; Iason Kountouridis; Courtney A Balgobin; Trudi Schüpbach; Rebecca D Burdine; Stanislav Y Shvartsman Journal: Proc Natl Acad Sci U S A Date: 2017-01-03 Impact factor: 11.205
Authors: Kyo Jin Jo; Yoo Mi Kim; Ju Young Yoon; Yeoun Joo Lee; Young Mi Han; Han-Wook Yoo; Hyang-Sook Kim; Chong Kun Cheon Journal: Korean J Pediatr Date: 2018-12-03
Authors: Alicia Romano; Juan Pablo Kaski; Jovanna Dahlgren; Nicky Kelepouris; Alberto Pietropoli; Tilman R Rohrer; Michel Polak Journal: Endocr Connect Date: 2022-01-31 Impact factor: 3.335
Authors: Catherine Tcheandjieu; Matthew Aguirre; Stefan Gustafsson; Priyanka Saha; Praneetha Potiny; Melissa Haendel; Erik Ingelsson; Manuel A Rivas; James R Priest Journal: PLoS Genet Date: 2020-11-23 Impact factor: 5.917