title: Orthopaedic conditions in Ras/MAPK related disorders.
abstract: BACKGROUND
  The RAS/MAPK disorders [Noonan syndrome, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, and Leopard syndrome] are heterogenous conditions with phenotypic overlap. Their orthopaedic manifestations are not well defined, and their phenotypic similarity makes differentiating them difficult.
  
  
  METHODS
  We prospectively evaluated 60 individuals: 26 with Noonan syndrome, 32 with CFC syndrome, and 2 with Costello syndrome. Each individual underwent a structured orthopaedic history and physical evaluation by an orthopaedic surgeon, and a syndromic evaluation by a geneticist.
  
  
  RESULTS
  All groups had a high prevalence of scoliosis (8/26 Noonan syndrome, 8/32 CFC syndrome, and 1/2 Costello). Those with Noonan syndrome or CFC syndrome had a high instance of serious cervical spine disorders, including cervical stenosis, Arnold-Chiari malformation, and syringomyelia in the Noonan syndrome individuals and hydrocephalus, cervical stenosis, torticollis, and Arnold-Chiari in the CFC syndrome individuals. Noonan syndrome manifestations included chronic pain (n=21), pes planus (n=11), pes cavus (n=5), hip contractures (n=5), hand dysfunction (n=3), and hip dysplasia (n=2). Manifestations of CFC syndrome included pes planovalgus (n=20), knee flexion contractures (n=7), hip dysplasia (n=5), elbow flexion contractures (n=4), pedal calluses (n=4), toe crowding (n=4), and hip contractures (n=4). Individuals with Costello syndrome had shorter stature than the other groups and were prone to have hand contractures.
  
  
  CONCLUSIONS
  Orthopaedic manifestations are frequent and diverse in Ras/MAPK disorders and can be used in phenotypic differentiation between these disorders.
  
  
  METHODS
  II.
authors.affiliation: Department of Orthopaedics, University of Texas Health Sciences Center, San Antonio, TX, USA. kreinker@mac.com
authors.forename: Kent A
authors.initials: KA
authors.lastname: Reinker
authors.forename: David A
authors.initials: DA
authors.lastname: Stevenson
authors.forename: Ann
authors.initials: A
authors.lastname: Tsung
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D001139:Arnold-Chiari Malformation / Q000150:complications* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004476:Ectodermal Dysplasia / Q000150:complications* / Q000235:genetics; D019066:Facies; D005183:Failure to Thrive / Q000150:complications* / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000150:complications* / Q000235:genetics; D006801:Humans; D015994:Incidence; D007223:Infant; D044542:LEOPARD Syndrome / Q000150:complications* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D009140:Musculoskeletal Diseases / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D009154:Mutation; D009634:Noonan Syndrome / Q000150:complications* / Q000235:genetics; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11