title: Response to growth hormone therapy in children with Noonan syndrome: correlation with or without PTPN11 gene mutation.
abstract: OBJECTIVE
  The objective of this study was to evaluate the efficacy of recombinant human growth hormone (rhGH) therapy and the influence of genotype on the response to rhGH therapy in children with Noonan syndrome (NS).
  
  
  METHODS
  14 male and 4 female subjects with NS with short stature, whose height was < 3rd percentile, were included. The rhGH was subcutaneously administered at a dose of 66 μg/kg/day. Mutations in the PTPN11 gene were identified in 10 subjects (55.6%). Mutations in the SOS1 (2 children, 11.1%), MEK1 (1 child, 5.6%) and KRAS (1 child, 5.6%) genes were also found.
  
  
  RESULTS
  Height SDS increased from –2.8 ± 0.9 at the start of rhGH therapy to –2.0 ± 0.9 12 months later (p < 0.001). Height velocity increased from 5.0 ± 0.9 cm/year in the year before treatment to 8.9 ± 1.6 during treatment (p < 0.001). Changes in height SDS, height velocity, and serum IGF-1 level did not differ significantly between those children with or without PTPN11 mutations.
  
  
  CONCLUSIONS
  The rhGH therapy significantly improved the growth velocity and increased the serum IGF-1 level. Longterm correlation between genotype and rhGH therapy responsiveness needs to be addressed in a large population.
authors: Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jin-Ho
authors: JH
authors: Choi
authors: Beom Hee
authors: BH
authors: Lee
authors: Chang-Woo
authors: CW
authors: Jung
authors: Yoo-Mi
authors: YM
authors: Kim
authors: Hye Young
authors: HY
authors: Jin
authors: Jae-Min
authors: JM
authors: Kim
authors: Gu-Hwan
authors: GH
authors: Kim
authors: Jin Soon
authors: JS
authors: Hwang
authors: Sei Won
authors: SW
authors: Yang
authors: Jin
authors: J
authors: Lee
authors: Han-Wook
authors: HW
authors: Yoo
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000187:drug effects / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020125:Mutation, Missense / Q000502:physiology; D009634:Noonan Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11