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

Abstract

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.

• Authors: Jin-Ho Choi, Beom Hee Lee, Chang-Woo Jung, Yoo-Mi Kim, Hye Young Jin, Jae-Min Kim, Gu-Hwan Kim, Jin Soon Hwang, Sei Won Yang, Jin Lee, Han-Wook Yoo
• Journal: Hormone research in paediatrics (Horm Res Paediatr) Vol. 77 Issue 6 Pg. 388-93 ( 2012) ISSN: 1663-2826 [Electronic] Switzerland
• PMID: 22777296 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Human Growth Hormone
• PTPN11 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 11

Topics

• Adolescent
• Body Height (drug effects, genetics)
• Child
• Child, Preschool
• DNA Mutational Analysis
• Female
• Genetic Association Studies
• Human Growth Hormone (adverse effects, therapeutic use)
• Humans
• Longitudinal Studies
• Male
• Mutation, Missense (physiology)
• Noonan Syndrome (diagnosis, drug therapy, genetics)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (genetics)
• Recombinant Proteins (therapeutic use)
• Treatment Outcome