Response to growth hormone therapy in children with Noonan syndrome: correlation with or without PTPN11 gene mutation.

Background/aims: 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.

Conclusion: 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.