ECEESPE2025 Oral Communications Oral Communications 14: Growth Axis and Syndromes (6 abstracts)
Noonan syndrome in real life: Patient characteristics and response to growth hormone therapy in a genetically defined single-country multicentre cohort
Barbora Jírová 1 , Mária Najdeková 2 , Jana Černá 2 , Petra Dušátková 1 , Stanislava Koloušková 1 , Ivana Kotvalová 3 , Olga Magnová 4 , Dana Novotná 4 , Barbora Obermannová 1 , Renata Pomahačová 5 , Štěpánka Průhová 1 , Jiří Strnadel 2 , Marta Šnajderová 1 , Zdeněk Šumník 1 & Jan Lebl 1
1University Hospital Motol and 2nd Faculty of Medicine Charles University, Department of Paediatrics, Prague, Czech Republic; 2Department of Paediatrics, Faculty of Medicine, Ostrava University and University Hospital, Ostrava, Czech Republic; 3Department of Paediatrics, Faculty of Medicine HK, Charles University and University Hospital, Hradec Králové, Czech Republic; 4Department of Paediatrics, Faculty of Medicine, Masaryk University and University Hospital, Brno, Czech Republic; 5Department of Paediatrics, Faculty of Medicine Plzeň, Charles University and University Hospital, Pilsen, Czech Republic
JOINT3101
Background: The spectrum of genes associated with Noonan syndrome (NS) is growing and the real-life experience with management of these children is increasing; however, the genotype-phenotype correlation and a tailored management await further refinement.
Aim: To evaluate patient characteristics and the response to growth hormone (GH) therapy in a genetically defined large multicentre cohort of NS patients from a single country.
Patients and methods: Eighty-eight patients with NS (51 males) from five participating centres were included. Of these, 63 had a (likely) pathogenic variant in PTPN11; 10 in SOS1; and 15 in other genes (BRAF [2], HRAS [2], KRAS [3], LZTR [1], MAP2K1 [1], NRAS [1], RAF1 [3] and SHOC2 [2]). All completed at least the first year of GH therapy while fifteen patients had already achieved their final height following GH administration.
Results: Not surprisingly, parental height was shorter than the population mean (fathers, -0.33 SDS [-1.33;0.57; median and IQR; P=0.001], mothers, -0.60 SDS [-1.47;0.12; P<0.0001]. The SOS1-patients were born earlier (GW 38 [32.5;38.3]) if compared to PTPN11-patients (GW 39 [38;40]; P<0.001). In the whole cohort of children, birth length was apparently lower (-1.26 SD [-1.78;-0.55] than the birth weight (-0.35 SD [-1.14;0.55; P<0.0001] demonstrating intrauterine bone growth restriction. Interestingly, both birth length and weight were lower in the PTPN11 and SOS1 patients if compared to the non- PTPN11-non- SOS1 subcohort (P<0.05). GH stimulation testing was performed in 47/88 patients, with a peak GH of 7.8 mg/l [5.0;10.4]. Subsequently, GH therapy was started at age 5.7 years (3.8;9.3) with height-SDS -3.09 (3.74;2.59). The median annual height-SDS increments were 0.61 (year 1; n=88); 0.29 (year 2; n=70); 0.21 (year 3; n=57); 0.11 (year 4; n=51); and 0.09 (year 5; n=34), and were similar regardless the causative gene. The subcohort with final height already known (n=15) started GH therapy later (at 9.0 years [5.8;11.8] with height-SDS -3.48 (-3.86;-3.05). Following similar height increments, they reached height-SDS -2.00 (-3.26;-1.63) at pubertal onset (aged 12.5 years [11.5;14.3]), and final height-SDS -2.07 (-2.65;-1.08; aged 18.0 years [16.0-18.9]).
Conclusions: Growth restriction in NS has a prenatal component that is apparent in PTPN11- and in SOS1-patients, but not in the non- PTPN11-non- SOS1 subcohort. GH therapy leads to a clinically significant improvement of statural height in all genetic subcohorts. In those with a known final height, the height increment occurred prior to pubertal onset; the pubertal portion of growth did not further improve final height. Thus, earlier initiation of therapy within childhood may optimize growth outcomes.
Volume 110
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