Ectatic Coronary Arteries in Noonan Syndrome

A 12-year-old girl with Noonan syndrome had severe right ventricular outflow tract obstruction, a small atrial septal defect, and hypertrophic cardiomyopathy. Other echocardiographic findings were severe subvalvular and valvular pulmonary stenosis (the 9-mm annulus was not amenable to balloon dilation), tricuspid valve dysplasia with mixed moderate tricuspid stenosis and moderate regurgitation, and systolic anterior motion of the mitral valve with moderate regurgitation. Ventriculography confirmed these findings (Fig. 1). There was no gradient across the left ventricular outflow tract and no aortic coarctation. The left ventricular angiogram showed dilated coronary arteries, so selective coronary injections were performed. The entire right, proximal and mid left anterior descending, and proximal left circumflex coronary arteries were ectatic (Fig. 2).

Fig. 1 Right ventriculogram (anteroposterior cranial view) in A) diastole and B) systole shows a hypertrophied ventricle, valvular and subvalvular pulmonic stenosis (arrows), and mild pulmonary artery bifurcation narrowing. C) Systolic frame of left ventriculogram (right anterior oblique view) reveals hypertrophy and moderate mitral regurgitation.

Fig. 2 Coronary angiography. A) Selective right coronary injection (left anterior oblique cranial view) reveals the ectatic right coronary artery. Left coronary angiograms in B) right and C) left anterior oblique cranial views show the ectatic proximal and mid left anterior descending coronary artery (arrows) and proximal left circumflex coronary artery (arrowhead).

Comment

Noonan syndrome is a cardiofacial syndrome with autosomal dominant inheritance, typical phenotypic findings, and well-characterized intracardiac malformations. The common cardiac malformations include stenosed and dysplastic pulmonary valve, atrial septal defect, and hypertrophic cardiomyopathy. Vascular abnormalities (rarely reported) include sinus of Valsalva aneurysms,¹ aortic dissection,² intracranial aneurysms, and coronary artery lesions. There are only 6 reported cases of the coronary artery lesions. The reported coronary anomalies include coronary artery fistula and dilation.^3–6 The association of these lesions with Noonan syndrome is not well understood. Several pathologic mechanisms have been proposed, including vasculitis superimposed upon a connective-tissue defect,⁵ dilation secondary to associated myocardial hypertrophy,⁴ and persistent aneurysm after the spontaneous closure of fetal coronary artery fistula.^3,4 More than 50 mutations have been identified in gene PTPN11, located at 12q24, the Noonan syndrome locus.⁷ This gene carries instructions for making the SHP-2 protein (tyrosine phosphatase), which is crucial to the embryonic development of the heart, blood cells, bones, and other tissues. Mutations involving PTPN11 may therefore result in connective-tissue defects that lead to the cardiovascular abnormalities in Noonan syndrome. All patients with Noonan syndrome should be carefully examined for coronary anomalies, and coronary angiography should be performed when warranted.