Espressioni emorragiche ed emostasi nella Sindrome di Noonan

Abstract

Noonan syndrome (NS) is a congenital disorder, inherited as an autosomal dominant trait, characterized by dysmorphic facies, congenital heart defects, short stature and other anomalies including coagulation abnormalities not fully studied so far. The aim of this study was to evaluate phenotypic characteristics, gene mutations, and coagulation parameters in 19 clinically diagnosed cases of NS (10 M, 9 F, 12 probands and 7 first degree relatives), 16 were mutation-positive: PTPN11 (n.7), SOS1 (n.8) and SOS1/RAF1 (n.1), and the remaining 3 were mutation-negative. A positive history for abnormal bleeding was found in 9 patients (47%), a prolonged PTT in 5 individuals (26%), coagulation factors deficiency in 9 patients (47%) and abnormal platelet aggregation in 8 patients (44%); the coagulation abnormalities were found either in the 9 patients with a history of abnormal bleeding either in 6 cases (60%) without clinical evidence of bleeding disorders. The coagulation abnormalities were reported both in patients carrying mutations in NS specific genes and in those mutations-negative and were not correlated with a mutation of a specific gene. Important differences in haemostatic status were found between probands and their relatives as the former showed coagulation abnormalities in the majority of the cases while the latter showed a history of bleeding diathesis, but normal laboratory hematological screen. The coagulation abnormalities were more frequent in patients with heart defects; however, a history of bleeding diathesis was detected in patients without cardiopathy. In conclusion, a high frequency of coagulation abnormalities has been found in NS. These abnormalities do not seem to be related with the patients genotype, considering the multiplicity of the unrelated types of bleeding abnormalities and the variability of their expression. The heart defects should not to be the only cause of the haemostatic disorders. The bleeding disorders, as well other phenothypic NS features, tend to decrease with age. Our advice is to screen every patients with NS for a bleeding diathesis to avoid bleedings and post-operative complications.