Comparison of effectiveness of growth hormone therapy according to disease-causing genes in children with Noonan syndrome.

Purpose: In the present study, the growth response following growth hormone (GH) therapy in prepubertal patients with Noonan syndrome (NS) harboring different genetic mutations was analyzed.

Methods: Twenty three patients with prepubertal NS were enrolled in the study at Pusan National University Children's Hospital, between March 2009 and July 2017. According to disease-causing genes identified, patients with NS were divided into four groups. Three groups were mutation-positive groups in three genes, PTPN11, RAF1, and SOS1, respectively. Five genes undetected (FGU) group refers to mutation-negative group in five genes, PTPN11, RAF1, SOS1, KRAS, and BRAF. The influence of genotype was retrospectively analyzed by comparing the growth parameters after GH therapy.

Results: The mean chronological age at the start of GH treatment was 5.85±2.67 years. At the beginning of GH treatment, height standard deviation score (SDS), growth velocity (GV), and IGF-1 levels were not statistically different among the groups. Among all 23 NS patients, height SDS and serum IGF-1 significantly increased during the 3 years of treatment. GV during the first year of treatment was highest. During the 3 years of GH therapy, PTPN11, RAF1, and SOS1 groups showed less improvement in height SDS, IGF-1 SDS, GV, and less increase in BA/CA ratio than FGU group.

Conclusions: The 3-year GH therapy in the 23 prepubertal patients with NS was effective in improving height SDS, GV, and serum IGF-1 levels. FGU group showed a better response to rhGH therapy compared with the detected groups with PTPN11, RAF1, and SOS1 groups.