ESPE Abstracts (2015) 84 P-3-944


The Impact of GH Therapy in Noonan Syndrome Children with Identified Mutations in RAS/MAPK Pathway

Alexsandra Malaquiasa,b, Michelle Moraesb,c, Mariana Funarid, Alexandre Pereirae, Debora Bertolac & Alexander Jorgeb,d


aDepartamento de Pediatria, Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo, Sao Paulo, Brazil; bUnidade de Endocrinologia-Genetica, LIM/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil; cUnidade de Genetica, Instituto da Crianca, FMUSP, Sao Paulo, Brazil; dLaboratorio de Hormonios e Genetica Molecular (LIM/42), Unidade de Endocrinologia do Desenvolvimento, Hospital das Clinicas, FMUSP, Sao Paulo, Brazil; eLaboratorio de Genetica e Cardiologia Molecular, Instituto do Coraçao (InCor), Sao Paulo, Brazil

Objective: To evaluate the response to recombinant human GH (rhGH) treatment in NS children with short stature and previously identified mutations in the RAS/MAPK pathway genes.

Methods: 23 patients with NS (17 males; 19 PTPN11, 3 RAF1 e 1 SHOC2) were daily treated with rhGH (mean rhGH dose of 47 μg/kg per day). The main outcome measures were 1st year growth velocity, change in height SDS (Noonan syndrome specific), change in IGF1 levels and adult height SDS.

Results: At the start of rhGH treatment, the mean age was 10.7±3.7 years, bone age was 8.6±3.2 years and 18 children were prepubertal. All subjects presented a height SDS <−2 for reference population (H-SDS=−3.4±0.8) and appropriate BMI-SDS. Noonan syndrome specific height SDS (HNS-SDS) was −0.8±0.7. Growth velocity (GV) during the 1st year of therapy was 7.0±2.0 cm/year, an increment of 2.9±.3.2 in baseline GV. Height SDS significantly improved after 1 year of rhGH therapy (mean change in HNS-SDS of 0.5±0.4, P<0.001). IGF1 levels also increases during the first year of therapy (99.7±56 μg/l to 237±104 μg/l, P<0.001). Adult height was achieved in eight patients (six PTPN11, one RAF1, one SHOC2) after 3.5 years of treatment. The total height SDS gain in relation to Noonan syndrome specific growth chart was 1.0±1.3, equivalent of 7 cm. No clear genotype influences on treatment outcomes were observed.

Conclusions: The use of rhGH to promote linear growth in short children with NS is still controversial. The increment of height SDS in relation to population matched Noonan syndrome specific growth chart support a benefit of this therapy to improve the adult height.

Funding: This work was supported by the FAPESP 2014/09410-0.

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