title: Growth patterns of patients with Noonan syndrome: correlation with age and genotype.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: EndocrineBone Diseases, and Genetics Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France.
authors.forename: Catie
authors.initials: C
authors.lastname: Cessans
authors.affiliation: UMR 1027 INSERMUniversity of Toulouse Paul Sabatier, Toulouse, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Ehlinger
authors.affiliation: UMR 1027 INSERMUniversity of Toulouse Paul Sabatier, Toulouse, France Clinical Epidemiology UnitToulouse University Hospital, Toulouse, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Arnaud
authors.affiliation: INSERM UMR 1048Institute of Cardiovascular and Metabolic Diseases (I2MC), University of Toulouse Paul Sabatier, Toulouse, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Yart
authors.affiliation: Departments of GeneticsRobert-Debré University Hospital, APHP, Paris, France.
authors.forename: Yline
authors.initials: Y
authors.lastname: Capri
authors.affiliation: Pediatric Endocrinology DepartmentClinical investigation Centre (CIC 1401), Bordeaux University Hospital, Bordeaux, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Barat
authors.affiliation: Pediatric Endocrinology DepartmentClinical investigation Centre (CIC 1401), Bordeaux University Hospital, Bordeaux, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Cammas
authors.affiliation: Genetics DepartmentBordeaux University Hospital, EA4576, Bordeaux, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: Pediatric Endocrinology DepartmentAngers University Hospital, Angers, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Coutant
authors.affiliation: Genetics DepartmentNantes University Hospital, Nantes, France.
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.affiliation: Pediatric Endocrine UnitNantes University Hospital, Nantes, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Baron
authors.affiliation: Pediatric Endocrine UnitLille University Hospital, Lille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.affiliation: Pediatric and Genetics UnitNancy University Hospital, Vandoeuvre, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.affiliation: Pediatric Endocrinology DepartmentLyon University Pediatric Hospital, INSERM U.1060/UCBL/HCL, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Nicolino
authors.affiliation: 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.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Salles
authors.affiliation: Departments of GeneticsRobert-Debré University Hospital, APHP, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.affiliation: 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.
authors.forename: Maithé
authors.initials: M
authors.lastname: Tauber
authors.affiliation: Departments of GeneticsRobert-Debré University Hospital, APHP, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Edouard
mesh_terms: D000328:Adult; D000367:Age Factors; D001724:Birth Weight; D001827:Body Height; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009634:Noonan Syndrome / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult