Genotype – Phenotype Correlations in Noonan Syndrome

Abstract

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.

DeepGestalt - Identifying Rare Genetic Syndromes Using Deep Learning

“…A set of 25 images, five images per gene (type), are excluded from training and used as a test set. Those images were curated from [58], [59], [57], [60], [61], [62]. To illustrate the general appearance of each cohort, we create composite photos by averaging the images of each cohort, see Figure 3.…”

Modeling age‐specific facial development in Williams–Beuren‐, Noonan‐, and 22q11.2 deletion syndromes in cohorts of Czech patients aged 3–18 years: A cross‐sectional three‐dimensional geometric morphometry analysis of their facial gestalt

“…Thus far, there are not many studies looking into correlations between facial features of patients with RASopathies and their genotype; however, there are genotype–phenotype correlations concerning stature, type of heart defect, psychomotor development, and skin conditions (Allanson et al, ; Aoki et al, ; Rusu, Idriceanu, Bodescu, Anton, & Vulpoi, ; Tartaglia et al, ; Zenker et al, ). In this regard, 3D facial gestalt “phenotyping” is promising.…”