July - September 2014, Volume 10, Issue 3

Rusu C, Idriceanu J, Bodescu I, Anton M, Vulpoi C

Genotype – Phenotype Correlations in Noonan Syndrome

Acta Endo (Buc) 2014, 10 (3): 463-476
doi: 10.4183/aeb.2014.463

Our study aimed to evaluate clinical, endocrine and genetic aspects in three patients with Noonan syndrome and to establish genotype – phenotype correlations. Noonan syndrome is a frequent autosomal dominant disorder, characterized by distinctive facial features, short stature, congenital heart defects, unusual chest shape, broad/ webbed neck, cryptorchidism and developmental delay. GH therapy initiated early adds 1 SD to final adult height. We have identified common features that are very suggestive for the diagnosis, as well as the changing of facial aspect in time. In case 2 we recorded a milder phenotype than expected for KRAS mutations. In case 3 we identified new features (severe scoliosis and ventricular septal defect) as well as more severe clinical features than expected for SOS 1 mutations. We have detected particular patterns of growth in our patients before and after GH therapy. Unlike literature data, our PTPN11 mutation positive child reacted very well to GH, whereas our KRAS mutation positive case started to gain Ht only after 3 years of GH therapy. We have recorded hypertrophic scars either as a new feature of NS, or as a possible adverse event of GH therapy. GH therapy was successful in our patients, without classical adverse events recorded. Somatotropic axis dysfunction is discussed.

Keywords: Noonan syndrome, genotype - phenotype correlation, GH therapy

Correspondence: Cristina Rusu MD, “Grigore T Popa” University of Medicine and Pharmacy - Medical Genetics, Str Universitatii 16, Iasi, 700115, Romania, E-mail: abcrusu@gmail.com