title: A pilot study of discontinuous, insulin-like growth factor 1-dosing growth hormone treatment in young children with FGFR3 N540K-mutated hypochondroplasia.
abstract: OBJECTIVE
  To assess the growth promoting effect of a recombinant growth hormone (rGH) treatment protocol adjusted on insulin-like growth factor 1 (IGF-1) dosing in children affected by the most severe forms of FGFR3 N540K-mutated hypochondroplasia.
  
  
  METHODS
  Midterm results of an open-label, single-center, nonrandomized, 2003-2020 pilot trial to final stature, including 6 children (mean age, 2.6 ± 0.7 years; mean height SDS, -3.0 ± 0.5) with the N540K mutation of FGFR3 gene who received an rGH dosage titrated to an IGF-1 level close to 1.5 SDS of the normal range. rGH therapy was interrupted 1 day per week, 1 month per year, and 6 months every 2 years.
  
  
  RESULTS
  The mean height SDS increased by 1.9 during the 6.1 ± 0.9-year study period, reaching -0.8 to -1.3 at age 8.7 ± 1 years. The mean±SDS baseline IGF-1 value was -1.6 ± 0.5 before rGH treatment and 1.4±0.3 during the last year of observation. The average cumulative rGH dose was 0.075 ± 0.018 mg/kg/day (range, 0.059-0.100 mg/kg/day). Trunk/leg disproportion was improved.
  
  
  CONCLUSIONS
  IGF-1-dosing rGH treatment durably improves growth and reduces body disproportion in children with severe forms of hypochondroplasia.
authors.affiliation: Service d'Endocrinologie Pédiatrique, Hôpitaux Universitaires Paris Sud, Paris, France.
authors.forename: Anya
authors.initials: A
authors.lastname: Rothenbuhler
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.forename: Catherine
authors.initials: C
authors.lastname: Piquard
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D001827:Body Height / Q000187:drug effects; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004392:Dwarfism / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005602:France; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D010865:Pilot Projects; D035583:Rare Diseases; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3