ESPE Abstracts

Introduction: Noonan Syndrome (NS) is a genetic disorder caused by mutations in the RAS/MAPK pathway. The clinical phenotype is variable; however, short stature is present in more than 80% of cases. Several clinical trials have been conducted over the last decades using recombinant growth hormone (rhGH) in NS to treat short stature demonstrating efficacy and safety which lead to the European Medicines Agency (EMA) approval in 2020.

Objective: Describe the efficacy and safety of rhGH treatment for short stature associated with NS in real life.

Subjects and Methods: Longitudinal study of subjects with clinical and genetic diagnoses of NS, with associated short stature (<-2.5 SD) who completed the first year of rhGH therapy. Data were collected during the clinical visits including clinical characteristics, genetic and laboratory study, anthropometric measurements, bone age, and rhGH dose.

Results: A total of 9 subjects were included; 5♂ / 4♀; 77,7% presented the genetic mutation in PTPN11; 7 of them had congenital heart disease, with pulmonary stenosis being the most common. The clinical characteristics of the subjects at the beginning of the treatment are described in Table 1. The rhGH dose administered was 0,038 ± 0,002 mg/Kg/day (range 0,035 to 0,040 mg/kg/day). After 12 months with rhGH there is a significant increase in height – SD from -2,96 ± 0,54 at baseline to -2,45 ± 0,53 at 12 months (P<0,0001). Growth velocity (GV) also increases from 4,8 ± 0,9 cm/year at baseline to 7,3 ± 1,8 cm/year at 12 months (P=0,002), as well as GV – SD from -0,51 ± 1,40 to 2,45 ± 2,21 (P=0,003). IG-1 - SD levels increased from -1,4 ± 1,24 at baseline to 0,21 ± 1,14 at 12 months. None of the IGF-1 values rose above +2 SD. No side effects were reported during the first year of rhGH treatment.

Conclusions: First year treatment with rhGH in NS with short stature improves height and GV. However, clinical follow-up of a greater number of cases until reaching adult height is necessary to determine the benefit of such treatment.