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infiltrate, and acute necrotizing vasculitis.351 Upon recovery, there can be multiple focal scars with residual myocardial dysfunction Drug-induced cardiomyopathies are most commonly attributed to alcohol, cobalt, and the anthracyclines They produce a dilated cardiomyopathy with poor contractility, leading to CHF Of these drugs, the anthracyclines are the most important, as they are widely used in the treatment of childhood cancer Miscellaneous Systemic Disorders Hutchinson-Gilford Progeria Progeria is a disease of premature aging frequently due to a mutation in the lamin A gene The defective gene product, progerin, undergoes abnormal posttranslational processing and leads to abnormal morphology of the nuclear envelope, with thickening of the nuclear lamina, loss of peripheral heterochromatin, blebbing of the nuclear envelope, and clustering of nuclear pores.352 The pathogenesis of plaque formation is different from typical adult atherosclerosis Children with Hutchinson-Gilford progeria have significant thickening of the adventitia, which may be due to the accumulation of progerin.353 Affected children are normal during the first months of life, exhibiting evidence of the disease in the second year with failure to thrive, loss of subcutaneous fat, scleroderma, alopecia, and the development of a typical facies This consists of a disproportionately large head for the face, a beaked nose, micrognathia, thin lips, and prominent eyes Skeletal abnormalities include dystrophic clavicles, thoracic deformities, knock-knees, persistent patency of the fontanelle, and osteoarthritis Intellectual development is normal.354 The cardiovascular system is affected by premature atherosclerosis of the coronary arteries and aorta Most patients have ischemic heart disease and suffer from myocardial infarctions or stroke, with death at a mean age of 13 years Some present with a dilated cardiomyopathy and cardiac failure with normal coronary arteries Calcification of the mitral and aortic valves is common.355 Function of the adrenal, thyroid, parathyroid, and pituitary glands is normal There is, however, resistance to insulin, and there are abnormal levels of lipids in the serum, with an increase in total lipids as well as pre-β and β lipoproteins Dietary treatment with reduction of the lipids to within the normal range does not seem to alter the course of the disease Arteriohepatic Dysplasia (Alagille Syndrome) Arteriohepatic dysplasia is characterized by chronic cholestasis It usually becomes apparent within the first 3 months of life with prolonged jaundice Involved infants may present later with a heart murmur.356 The other features making up this syndrome are a typical facies, vertebral malformations, peripheral pulmonary stenosis, and ocular involvement Delayed physical, mental, and sexual development has not been consistently reported.357 The disease is sometimes associated with defects in the JAG1 gene, which encodes a ligand for the notch transmembrane receptor.358 This signaling mechanism is important for vascular development.359 The characteristic facial appearance consists of a prominent forehead, deep-set eyes with mild hypertelorism, and a small pointed chin Ophthalmologic examination reveals chorioretinal atrophy and pigment clumping, which may be pathognomonic Peripheral pulmonary stenosis is the typical cardiovascular anomaly On physical examination, there is a prominent left parasternal impulse and an ejection systolic murmur at the upper left sternal border radiating to the back, where it may be heard extending into diastole The ECG shows right ventricular hypertrophy Cardiac size may be normal or increased on the chest radiograph, and the lung fields may appear normal or oligomeric Structural intracardiac disease is present in up to 1 in 4 patients, including tetralogy of Fallot with or without pulmonary atresia, valvar pulmonary stenosis, isolated atrial septal defect and ventricular septal defect.360 Many patients have anomalies of the vertebral arches, usually with a butterfly appearance of the dorsal vertebrae Xanthomas of the palms, extensor surfaces, and skin creases of the hands are seen when hyperlipidemia is present Elevated lipids and cholesterol in the serum are controlled by the use of cholestyramine and the addition of corn oil to the diet Arteriohepatic dysplasia is confirmed by liver biopsy, which shows the bile ducts to be absent from most portal areas Periportal fibrosis is absent or mild, and the extrahepatic system is patent Additional laboratory findings include elevated 5′-nucleotidase, alkaline phosphatase, transaminases, and bilirubin The peripheral pulmonary stenosis is not progressive and does not influence the long-term prognosis of the disease Liver dysfunction and complex congenital heart disease have been among the most prominent causes of mortality.361 Sickle Cell Hemoglobinopathy Sickle cell hemoglobinopathy is a chronic anemia that predominantly affects individuals of African descent The underlying abnormality is the substitution of glutamic acid by valine in the sixth position of the β chain of hemoglobin This results in the formation of hemoglobin S When the tension of oxygen is reduced, the hemoglobin S molecules polymerize and produce a crescent- or