Though a wide spectrum of cardiac pathology has been reported, pulmonary stenosis is the most common structural abnormality and more likely to be seen in PTPN11 mutations.
Cardiac anomalies including pulmonary stenosis and hypertrophic cardiomyopathy were most prevalent (87.2%), and the prevalence of hypertrophic cardiomyopathy was greater in patients without PTPN11 mutations than in those with PTPN11 mutations.
We conclude that (a) most of our clinically diagnosed NS cases were sporadic (b) PTPN11 analysis should be limited to those fulfilling the relevant NS criteria (c) Cardiovascular evaluation should comprise all NS patients, while pulmonary stenosis, short stature, and thorax deformities prevailed among those with PTPN11 mutations.
In our total cohort, patients with NS and a PTPN11 mutation presented significantly higher prevalence of short stature (p = 0.03) and pulmonary valve stenosis (p = 0.01), and lower prevalence of hypertrophic cardiomyopathy (p = 0.01).
Pulmonary valve stenosis and atrial septal defect, ostium secundum type, were significantly associated with the identification of a mutation in the PTPN11 gene.
Six of eight subjects with PTPN11/SHP2 mutations had pulmonary valve stenosis while no mutations were identified in those subjects (N = 4) with hypertrophic cardiomyopathy.