CARDIOLOGIC ABNORMALITIES IN NOONAN SYNDROME - PHENOTYPIC DIAGNOSIS AND ECHOCARDIOGRAPHIC ASSESSMENT OF 118 PATIENTS

Objectives. The purpose of this study was to determine the incidence o f cardiologic abnormalities in Noonan syndrome. Background. The incide nce of cardiac abnormalities in Noonan syndrome remains unknown, large ly because of such difficulties as assembling a substantial cohort, en suring a correct phenotypic diagnosis and providing accurate definitio ns of the most frequent abnormalities-pulmonary stenosis and left vent ricular hypertrophy. Methods. A cohort of 145 patients was assembled, and before cardiologic assessment two independent geneticists scrutini zed the phenotype. The diagnosis was confirmed in 118 patients, and th ey were studied by two-dimensional and Doppler echocardiography. Resul ts. A dysplastic pulmonary valve was present in eight patients (7%) an d was associated with significant stenosis in six (75%) of the eight. Significant stenosis was present in 22 (20%) of 110 patients without d ysplasia. Left ventricular hypertrophy was present in 29 patients (25% ) without significant pulmonary stenosis. Localized anterior septal hy pertrophy was the most common pattern in 12 (41%) of 29 patients. Diff use hypertrophy involving the entire septum and the free wall was pres ent in nine patients (31%) and was severe (>1.7 cm) in five. Other abn ormalities included secundum atrial septal defects (10%). Conclusions. The high incidence of cardiac abnormalities suggests that echocardiog raphic and Doppler evaluation of patients with the Noonan phenotype is important because it will aid in genetic counseling and in the assess ment of the natural history of-and, ultimately, identification of the gene(s) responsible for-Noonan syndrome.