Williams syndrome (WS) is characterized by developmental delay, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, cardiovascular disease (supravalvar aortic stenosis, peripheral pulmonary stenosis, hypertension), connective tissue abnormalities, growth deficiency, endocrine abnormalities (early puberty, hypercalcemia, hypercalciuria, hypothyroidism), and distinctive facies. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones. Feeding difficulties often lead to poor weight gain in infancy.

Multiple types of congenital heart defects-2 (CHTD2) is characterized by variable congenital heart defects, primarily involving the valves, but also including septal defects or aneurysms, and complex defects such as tetralogy of Fallot. Dilated cardiomyopathy and myocardial noncompaction have been reported in some patients. In addition, some affected individuals exhibit facial dysmorphism and features of connective tissue disease (Thienpont et al., 2010; Ackerman et al., 2016; Ritelli et al., 2018). For a discussion of genetic heterogeneity of CHTD, see 306955.