ESPE Abstracts

Introduction: Noonan syndrome (NS) is caused by mutations in RAS/MAPK signaling pathway genes. About 70% of the NS patients have short stature, and human recombinant growth hormone (rhGH) is an established yet not fully standardized treatment.

Objective: To assess the first 2 years rhGH treatment effectiveness in NS patients at a single centre.

Materials and methods: A total of 20 (16 male) NS patients diagnosed clinically based on the van der Burgt criteria, and followed regularly (2011-2020) were included. Of these, 11 (55%) patients underwent DNA testing, 9 (45%) had cardiac defects, and 8 (40%) had short stature. GH deficiency (GHD) was confirmed in 5 patients who started rhGH treatment. Two additional patients were treated as small for gestational age children without postnatal catch-up. Bone age (BA, by Greulich&Pyle) was estimated at the start and once yearly thereafter. Patients underwent anthropometry, clinical and laboratory investigations 6-monthly, and echocardiography yearly. All patients had at least 2 years of follow-up after the start of rhGH treatment.

Results: DNA test results of the 7 rhGH treated patients showed that 2 (28.5%) had PTPN11 mutation, 1 (14.5%) had KRAS mutation, in 2 (28.5%) patients no mutation was found, and in 2 (28.5%) the genetic work-up is not yet finalised. The mean age at NS diagnosis was 7.8±3.4 years (1.3÷10.5), and at rhGH start 9.1±1.5 years (7.5÷10.7). The overall treatment period was 38.3±15.3 months. At the start of the rhGH therapy, SDS_height was -3.42±0.58 (-4.1 ÷ -2.6), SDS_weight -3.07±0.58 (-3.73 ÷ -2.27), and SDS_IGF1 -1.12±0.98 (-2.44÷ 0.25). The mean BA at diagnosis was delayed by 2.6±0.9 years. The rhGH starting dose was 0.035±0.005mg/kg/d, the 1st year dose was 0.036±0.002 mg/kg/d, increasing to 0.037±0.003 mg/kg/d during the 2nd year. The growth velocity for the 1st year of treatment was 8.9±1.4 cm, and for the 2nd year 6.9±1.1 cm. The first year ΔSDSheight was 0.72 (P = 0.002), ΔSDS_weight was 0.83 (P = 0.025). The 2nd year ΔSDS_height, ΔSDS_weight and ΔSDS_BMI increased insignificantly. The ΔSDS_IGF1 were 1.70 (P = 0.067) and 0.25 (n.s.), respectively. By the end of the 2nd year, the mean BA remained significantly delayed. No treatment side effects were observed.

Conclusion: Our study shows that NS patients follow the general patterns for the first 2 years of rhGH treatment. In order to improve outcomes, the treatment should be further standardized.