Williams syndrome is a genetic disorder that occurs in 1 in 20,000 to 1 in 50,000 live births.Reference Williams, Barratt-Boyes and Lowe 1 It is unusual to find an association of several cardiac lesions in the same Williams syndrome patient. In this report, we present the case of a child diagnosed with supravalvular aortic stenosis, subvalvular aortic membrane, mitral regurgitation, aortic coarctation, and patent ductus arteriosus in Williams syndrome, who had undergone a single-stage surgical repair.
Case report
A 22-month-old boy with a characteristic elfin facial appearance was admitted to our hospital because of a cardiac murmur (Fig 1a). The patient's medical history was remarkable for feeding difficulties, infantile irritability, decreased physical growth, and motor developmental disorders. The patient's mother had a history of mental retardation. Owing to the patient's peculiar face and mental retardation, fluorescence in situ hybridisation analysis was performed, which revealed the hybridisation signal on only one chromosome 7 in this patient.
Figure 1 ( a ) The boy had a characteristic elfin facial appearance. ( b ) A 2.2 mm diameter patent ductus arteriosus.
Blood pressure measured at the left arm was higher than the one measured at the left leg (130/40 mmHg, 90/35 mmHg, respectively). A chest X-ray showed an increased cardiothoracic ratio of 0.71 and an increased pulmonary vasculature. Electrocardiography suggested left ventricular hypertrophy. The serum calcium level (2.62 mmol/L) was normal.
Transthoracic echocardiography indicated mitral valve prolapse with moderate regurgitation and a typical hourglass-type stenosis just above the aortic valve without coronary stenosis. The pre-operative peak systolic pressure gradient between the left ventricle and ascending aorta was 26 mmHg. Echocardiography also demonstrated severe aortic coarctation with a 79-mmHg gradient measured across the descending aorta. Simultaneously, a 4-mm-diameter patent ductus arteriosus was detected. A haemodynamically insignificant subvalvular aortic membrane was demonstrated with an instantaneous pressure gradient of 12 mmHg. Chest computed tomography scan angiography revealed a short narrowing of the descending aorta distal to the origin of the left subclavian artery and a 2.2-mm-diameter patent ductus arteriosus (Fig 1b). The minimum diameter of the stenotic region on the descending aorta was 3.2 mm (Fig 2a). The minimum diameter of the supravalvular aortic stenosis was 6.5 mm (Fig 2b), while the diameter of the aortic arch is 9.7 mm.
Figure 2 ( a ) The minimum diameter of the stenotic region on the descending aorta was 3.2 mm. ( b ) The minimum diameter of supravalvular aortic stenosis was 6.5 mm.
The patient underwent a one-step surgery for repairing of all of the haemodynamically significant malformations through a median sternotomy. The ductus arteriosus was ligated and all ductal tissue was resected within the coarctation area. The anastomosis between the distal thoracic aorta and enlarged transverse aortic arch was performed using an extended end-to-end anastomosis. A longitudinal incision was made in the aorta just above the supravalvar stenosis, which showed significant stenosis of the sinotubular junction and extensive fibrosis of the aortic wall, whereas the coronary ostia were normal. The aortic incision was extended into the right and non-coronary sinuses and repaired with an inverted Y-shaped patch of autologous pericardium. Then, an extensive prolapse of all the posterior leaflet resulting from elongated chordae, was found to be the reason of the mitral regurgitation. Reduction annuloplasty with chordal shortening was used for correcting the posterior leaflet prolapse. The subvalvular aortic membrane was discrete, and resected totally. The cross-clamp time was 111 minutes and the total bypass time was 138 minutes.
The patient was discharged on the 9th post-operative day. After 5 months of the procedure, the patient was doing well and had no complaints. In addition, the echocardiogram showed that the systolic pressure gradient between the left ventricle and the ascending aorta improved to normal, and no gradient was measured across the descending aorta post-operatively. There was mild residual mitral regurgitation.
Discussion
Williams syndrome is characterised by typical faces, growth delay, mild mental retardation, and cardiovascular anomalies. The cardiovascular manifestations vary. Supravalvular aortic stenosis is the most common cardiac anomaly, which is present in 64% of patients.Reference Pham, Moller, Hills, Larson and Pyles 2 Other cardiopathies include pulmonary artery stenosis, aortic hypoplasia, aortic coarctation, mitral valve prolapse, and septal defects.Reference De Rubens Figueroa, Rodriguez, Hach, Del Castillo Ruiz and Martinez 3 Therefore, this disease should not be considered as an isolated entity.
The pathogenic mechanism underlying the Williams syndrome vasculopathy is not yet understood. Reduced and abnormal elastin content in the media of developing vessels may lead to recurrent injury and fibrosis. Vascular inelasticity may increase haemodynamic stress to the endothelium, leading to the production of fibrosis and increase of the middle layer by hypertrophy of muscle cells and collagen formation. These eventually lead to a luminal narrowing of the vessels.Reference Williams, Barratt-Boyes and Lowe 1 Owing to the fact that the vessel, at the site of the stenosis, does not grow proportionally to the patient's somatic growth, the haemodynamic burden produced by this stenosis gradually worsens over time. In the present case, the flow jet across the supravalvar aortic stenosis may have caused a predisposition to the development of an aortic coarctation. At the same time, the mitral regurgitation may be secondary to an increase in collagen in the mitral valve and left ventricular pressure overload. The underlying elastin arteriopathy is a generalised disease of both artery and heart valve.Reference Actis Dato, La Torre and Caimmi 4
Supravalvular aortic stenosis and aortic coarctation have similar haemodynamic changes and clinical features. When two aortic anomalies coexist, the patient may require prompt surgical correction because of the impairment of left ventricular function caused by stenosis-induced pressure overload.
In general, as shown by many surgical follow-up studies, aortic arch surgery can be performed safely and with excellent early and late results in children with supravalvular aortic stenosis.Reference Actis Dato, La Torre and Caimmi 4 In surgery to treat supravalvular aortic stenosis and aortic coarctation, the aim is to reduce the post-operative transaortic blood pressure gradient as much as possible. In the present case, we performed a coarctectomy with end-to-end anastomosis for treatment of the coarctation, considering the previous excellent results of this surgical technique in our and other centres.Reference English, Colan, Kanani and Ettedgui 5 Simultaneously, we used the technique described by DotyReference Doty 6 to treat supravalvular aortic stenosis. We believe that an inverted Y patch repair provides a good anatomical repair in correcting supravalvular aortic stenosis in children, and there may not be a need for more extensive and complex operations such as Brom's technique.Reference Doty, Polansky and Jenson 7
Although pulmonary artery branch stenosis tends to improve spontaneously, supravalvular aortic stenosis and aortic coarctation progress with age in Williams syndrome. In the face of such complex pathology, the single-stage repair is advantageous for correcting all pathology during a single operation. There is also evidence that early intervention may reduce the incidence of development of ostial coronary artery disease and ventricular dysfunction, thus conferring survival benefit.
