A pilot study of discontinuous, insulin-like growth factor 1-dosing growth hormone treatment in young children with FGFR3 N540K-mutated hypochondroplasia.

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. Study design 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. Conclusion IGF-1-dosing rGH treatment durably improves growth and reduces body disproportion in children with severe forms of hypochondroplasia. (J Pediatr 2012; 160: 849-53).