Hernias Renal malformation Hypertension 40 20 20 FIG 77.5 Facial appearance of Williams syndrome Cardiac Defects CHDs are diagnosed in 75% of the patients, manifesting as elastin arteriopathy In fact, the abnormal elastin protein characteristic for the syndrome causes proliferation of arterial smooth muscle and intimal hyperplasia resulting in arterial stenosis, in particular at supravalvar aortic and pulmonary artery levels (see Table 77.6), but also at mesenteric and renal artery levels with a tendency to arterial hypertension.60–62 Supravalvar aortic stenosis is generally a progressive lesion, which can occur both in the form of localized hourglass narrowing of the supravalvar area or diffuse narrowing extending into the aortic arch and into the origin of brachiocephalic arteries Stenoses of pulmonary arteries, on the contrary, often improve spontaneously in patients with this syndrome.60 The characteristics of peripheral vascularity, coronary arteries, and cerebral vessels of these patients may complicate both history or treatment procedures, such as cardiac catheterization, anesthesia, and surgery.61,63 Patients with Williams syndrome are at risk for systemic hypertension and myocardial anomalies, probably due to arterial structural anomalies.64 Due to the possible association with coronary artery stenosis, the preoperative and preinterventional assessment of these children must include coronary angiography, in particular in patients with supravalvar aortic stenosis In this syndrome, specific perioperative protocols are indicated to reduce the surgical risk.63 Genetic Defect The syndrome is caused by a submicroscopic deletion of chromosome 7q11.23, encompassing the elastin gene (ELN).65 More than 20 genes have been mapped inside the commonly deleted region, spanning approximately 1.5 megabases Many of the clinical features of Williams syndrome, including cardiac defect, are caused by the deletion of the elastin gene Monogenic Syndromes Rasopathies (Noonan Syndrome and Related Disorders) Clinical Features RASopathies are a genetically heterogeneous and clinically variable group of disorders transmitted through autosomal dominant inheritance Noonan syndrome and related disorders, including Noonan syndrome with multiple lentigines (also known as LEOPARD syndrome) and cardiofaciocutaneous (CFC) and Costello syndromes caused by mutations affecting several genes participating in the RAS/MAP kinase (MAPK) signaling pathway.66,67 Common clinical findings in RASopathies include growth defects and feeding difficulties, distinctive facial anomalies (Fig 77.6A–C), CHDs, webbed neck, cryptorchidism, and chest anomalies (Table 77.7).67