ESPE Abstracts (2014) 82 P-D-2-1-452

Rasopathies: Assessment of Growth, Genetic Study, Genotype-Phenotype Correlation and Therapeutic Response to GH in Noonan Syndrome

Claudia Herediaa,b, Francisco Barrosc, Lidia Castro-Feijóoa, Jesús Barreiro Condea, Paloma Cabanas Rodrígueza & Manuel Pombo Ariasa

aUnidad de Endocrinología Pediátrica, Crecimiento y Adolescencia, Hospital de Santiago de Compostela, Universidad de Santiago de Compostela, España, Santiago de Compostela, A Coruña, Spain; bHospital Militar Central, Bogotá, Colombia; cUnidad de Medicina Molecular, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain

Background: Rasopathies are a heterogeneous group of diseases that share phenotypic characteristics such as facial dysmorphism, congenital heart disease and short stature.

Objective and hypotheses: Evaluation of growth and study of the GH–IGF1 axis. Molecular Study of the PTPN11, SOS1, RAF, KRAS, NRAS, MAP2K1 and MAP2K2 genes. Evaluation of growth and study of the GH–IGF1 axis.

Method: Descriptive retrospective study in patients with suspected Rasopathies in the period 1993–2013 that have been studied in the Hospital Clínico Universitario de Santiago de Compostela.

Results: 25 patients with high suspicion of Rasopathies: 19 with Noonan syndrome (NS), three with Leopard syndrome, two with Cardio-facio-cutaneous syndrome and one with Neurofibromatosis-Noonan syndrome, distributed as follows: 56% girls (n=14) and 44% male (n=11). Gestational age mean was 39-week, average length −0.45 SDS. Target height: male −1.28 SDS and girls −0.85 SDS. During the first 2 years there was a decrease in the growth channels, predominantly in girls. The growth velocity of the group showed a delayed growth spurt, with later and less intense than in the Spanish population. 33% had values below the normal range for IGF1 and IGFBP3. Six patients (24%) were diagnosed with GHD and SN, the pretreatment height was −3.1SDS. After a year of treatment with GH we found an increased growth velocity to 8.14 cm/año in average and height variation was observed at −2.43 SDS. Molecular study demostrated a genetic disorder, like this: PTPN11 (n=8), SOS1 (n=2), RAF1 (n=1), NF1 (n=1) and MAP2K1 (n=1). Patients with mutations in PTPN11 had alterations in the EKG, associating with GH deficiency. The patient has RAF1 mutation had hypertrophic cardiomyopathy.

Conclusion: 59, 1% have a genetic mutation in any of the genes studied. 24% have associated GH deficiency. Treatment with GH in these patients appears to be effective.

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