Background: Noonan syndrome (NS) is a genetic multisystem disorder characterized by distinctive facial features, learning difficulties, short stature, and cardiac defects. Other important findings include skeletal anomalies, especially spinal and chest deformities. Skeletal dysplasia was proven to be secondary to a disorder of RAS-mitogen activated protein kinase (MAPK) pathway which is essential for regulation of cell differentiation and growth including bone homeostasis. We describe the pattern and severity of bone deformities and other related clinical characteristics in five patients with Noonan syndrome.
Methods: We reviewed the cases of five children with NS (three boys and two girls, aged between 5 and 13 years), evaluated at the Endocrinology Department between January 2010 and January 2013. Evaluation included clinical and hormonal data as well as radiographic assessment of deformities.
Results: All patients had specific phenotype for Noonan syndrome. Three had also a molecular confirmation (the first with KRAS mutation, the second PTPN11, and the third SOS1). All children had short stature, with a mean S.D. −3.27 in heights. Handwrist radiography showed a moderately delayed bone age in all patients. None of the patients had congenital bone deformities, and the birth weight and length were within normal ranges for gestational age. The most frequent skeletal anomaly was chest deformity four children had inferior pectus excavatum and two of them associated superior pectus carinatum. One patient, with SOS1 mutation, had scoliosis with double major curve, developed at age two. Another patient also associated cubitus valgus and slightly shortness of the fingers and toes.
Discussions: All five patients with Noonan syndrome had short stature with late bone development and skeletal deformities. Chest deformities are usually correlated with a PTPN11 positive genotype, confirmed in only one case of the four children with this type of skeletal anomaly. Scoliosis and kyphosis occur in about 15% of patients, mainly associated with SOS1 mutations, as it was in our case with severe double curved scoliosis. Since bone anomalies tend to develop early and some are relatively severe, patients require clinical and, if necessary, radiographic assessment with careful follow-up for early detection and treatment.
22 - 25 Jun 2013