A

Description

This syndrome, formerly known as DiGeorge syndrome, occurs in both males and females. These patients have a deletion of the long arm of chromosome 22 (22q11.2) detectable with the fluorescence in situ hybridization (FISH) technique.

B

Clinical Manifestations

Clinical features of the syndrome are collectively grouped under the acronym of CATCH-22 ( c ardiac, a bnormal facies, t hymic hypoplasia, c left palate, and h ypocalcemia resulting from 22 q11 deletion).

• 1.
  

  C ardiac. The great majority of patients (85%) with the syndrome have serious CHDs. The common ones include TOF (25%), interrupted aortic arch (15%), VSD (15%), persistent truncus arteriosus (9%), and isolated aortic arch anomalies (5%).

  
  
• 2.
  

  A bnormal facies: hypertelorism, micrognathia, short philtrum with fish mouth appearance, antimongoloid slant, telecanthus with short palpebral fissures, and low-set ears, often with defective pinna.

  
  
• 3.
  

  T hymic hypoplasia or aplasia, with mild to moderate decrease in T-cell number.

  
  
• 4.
  

  C left: anomalies in the palate (70% to 80%) with speech and feeding disorders.

  
  
• 5.
  

  H ypocalcemia (60%) is due to hypoparathyroidism.

  
  
• 6.
  

  General. Short stature, mental retardation, and hypotonia in infancy are frequent. Occasionally, psychiatric disorders (e.g., schizophrenia and bipolar disorder) develop.

C

Management

• 1.
  

  Correction of cardiac malformation is required; cardiac defects are major causes of early death.

  
  
• 2.
  

  Irradiated, cytomegalovirus-negative blood products must be administered because of the risk of graft-versus-host disease with nonirradiated products.

  
  
• 3.
  

  Monitoring of serum calcium levels and supplementation of calcium and vitamin D are important.

  
  
  
  
  • a.
    

    Calcium gluconate, 500 to 750 mg/kg/day, PO, every 6 hours, or calcium carbonate, 50 to 150 mg/kg/day, PO, every 6 hours.

    
    
  • b.
    

    Ergocalciferol (vitamin D ₂ ), 25,000 to 200,000 U PO QD.

  
  
  
  
• 4.
  

  Live vaccines are contraindicated in patients with 22q11 deletion syndrome and in household members because of the risk of shedding live organisms.

  
  
• 5.
  

  Early thymus transplantation may promote successful immune reconstitution.

A

Description

This autosomal recessive disease manifests with the onset of ataxia usually before age 10 years and progresses slowly, involving the lower extremities to a greater extent than the upper extremities. Explosive dysarthric speech and nystagmus are characteristic, but intelligence is preserved.

B

Cardiovascular Manifestations

• 1.
  

  Cardiomyopathy is found in approximately 30% of the cases. Hypertrophic cardiomyopathy with normal LV systolic function is the most common finding. In advanced stage, the LV enlarges, the LV wall thickness decreases, and LV systolic function decreases. CHF is the terminal event, with most patients dying before age 40 years.

  
  
• 2.
  

  The electrocardiogram (ECG) may show the T vector change in the limb leads or left precordial leads. Occasionally, LVH, RVH, abnormal Q waves, or short PR intervals are found.

C

Management

The same as described for cardiomyopathy.

A

Description

• 1.
  

  Hyperthyroidism results from excess production of T ₃ (triiodothyronine), T ₄ (thyroxine), or both. The level of thyroid-stimulating hormone (TSH) is suppressed.

  
  
• 2.
  

  The actions of thyroid hormone on the CV system include (a) increasing heart rate, cardiac contractility, and cardiac output; (b) increasing systolic pressure and decreasing diastolic pressure, with mean pressure unchanged; and (c) increasing myocardial sensitivity to catecholamines.

B

Clinical Manifestations

• 1.
  

  Congenital hyperthyroidism (neonatal Graves disease): an anxious, irritable, and unusually alert baby with widely open eyes (exophthalmic). Many of the infants are premature and most have goiters.

  
  
• 2.
  

  Children with juvenile hyperthyroidism (Graves disease) are hyperactive, irritable, and excitable. The patients have exophthalmos and a goiter. There is a 5:1 female-to-male ratio.

  
  
• 3.
  

  Cardiovascular manifestations include tachycardia, full and bounding pulses, and increased systolic and pulse pressures. Bruits may be audible over the enlarged thyroid in children but not in newborns. In severely affected patients, cardiac enlargement and cardiac failure may develop.

  
  
• 4.
  

  Chest radiographs usually are normal unless CHF develops.

  
  
• 5.
  

  The ECG may show sinus tachycardia, peaked P waves, various arrhythmias (SVT, junctional rhythm), complete heart block, RVH, LVH, or biventricular hypertrophy.

  
  
• 6.
  

  Echo studies reveal a hyperkinetic LV with increased fractional shortening.

C

Management

• 1.
  

  In severely affected patients, a β-adrenergic blocker such as propranolol is indicated to reduce the effect of catecholamines.

  
  
• 2.
  

  Treatment of hyperthyroidism consist of oral administration of antithyroid drugs, propylthiouracil or methimazole (Tapazole).

  
  
• 3.
  

  If CHF develops, treatment with anticongestive medications is indicated.

A

Description

• 1.
  

  Congenital type. Clinical signs may not appear until 3 months of age. A protuberant tongue, cool and mottled skin, subnormal temperature, carotenemia, and myxedema are typical. Untreated children become mentally retarded and slow in physical development.

  
  
• 2.
  

  Acquired type. It may be caused by lymphocytic thyroiditis (Hashimoto disease or autoimmune thyroiditis), subtotal or complete thyroidectomy, or protracted ingestion of goitrogens, iodides, or cobalt medications. Rarely, amiodarone can cause hypothyroidism. Serum T ₃ and T ₄ are low or borderline and TSH is high. Hypercholesterolemia is common.

B

Cardiovascular Manifestations

• 1.
  

  Significant bradycardia, weak arterial pulse, hypotension, and nonpitting facial and peripheral edema may be present.

  
  
• 2.
  

  The ECG abnormalities may include some or all of the following: low QRS voltages, especially in the limb leads; low T-wave amplitude; prolongation of PR and QT intervals; and dome-shaped T wave with an absent ST segment (“mosque” sign).

  
  
• 3.
  

  Echo studies may show pericardial effusion, hypertrophic cardiomyopathy, or asymmetric septal hypertrophy.

  
  
• 4.
  

  In congenital type, PDA and PS are frequently found.

  
  
• 5.
  

  There is an increased occurrence of hypercholesterolemia in acquired type.

C

Management

• 1.
  

  L-thyroxine given orally is the treatment of choice. Monitor T ₄ and TSH frequently.

  
  
• 2.
  

  In acquired type, treatment of hypercholesterolemia, if present.

A

Description

• 1.
  

  In general, infants of diabetic mothers (IDM) have higher prevalence of congenital malformations of multiple organ systems, occurring at three to four times the rate seen in the general population. Common ones include neural tube defects (anencephaly, myelomeningocele), CHDs (such as ASD, VSD, TGA, tricuspid atresia, COA, etc.), and sacral dysgenesis or agenesis.

  
  
• 2.
  

  In addition to the high prevalence of congenital anomalies, IDMs have a high prevalence of cardiomyopathy and persistent pulmonary hypertension of newborn (PPHN).

  
  
  
  
  • a.
    

    Hypertrophic cardiomyopathy (either concentric or asymmetric septal hypertrophy) with or without obstruction is seen in 10% to 20% of the patients.

    
    
  • b.
    

    An increased risk of PPHN may be due to conditions that promote the persistence of pulmonary hypertension, such as hypoglycemia, perinatal asphyxia, respiratory distress, and polycythemia.

  
  

B

Clinical Findings of Cardiomyopathy

• 1.
  

  Signs of CHF with gallop rhythm may be found in 5% to 10% of these babies.

  
  
• 2.
  

  Chest radiographs may show varying degrees of cardiomegaly with normal or increased PVM.

  
  
• 3.
  

  The ECG may show a long QT interval (caused by hypocalcemia) and occasional RVH, LVH, or BVH.

  
  
• 4.
  

  Echo findings of cardiomyopathy in IDMs may include the following.

  
  
  
  
  • a.
    

    An increase in the LV wall thickness, often with asymmetric septal hypertrophy, and supernormal contractility of the LV.

    
    
  • b.
    

    Evidence of LVOT obstruction (seen in about 50% of cases).

    
    
  • c.
    

    Rarely, the LV is dilated with decreased contractility (dilated cardiomyopathy).

  
  

C

Management

• 1.
  

  Hypoglycemia and hypocalcemia should be corrected, if present.

  
  
• 2.
  

  In most cases, the hypertrophy spontaneously resolves within the first 6 to 12 months of life. β-Adrenergic blockers, such as propranolol, may help reduce the LVOT obstruction, but treatment usually is not necessary.

  
  
• 3.
  

  Digitalis and other inotropic agents are contraindicated because they may worsen the obstruction.

  
  
• 4.
  

  If CHF develops, the usual anticongestive measures are indicated.

A

Description

Marfan syndrome is a generalized connective tissue disease involving skeletal, cardiovascular, and ocular systems. Mutation in the FBN1 gene located on chromosome 15 is the cause of Marfan syndrome. It is inherited as an autosomal dominant pattern with variable expressivity. New mutations are the cause of at least 25% of Marfan syndrome cases.

• 1.
  

  Skeletal: tall stature with long slim limbs, arachnodactyly, muscle hypotonia, joint laxity with scoliosis and kyphosis, pectus excavatum or carinatum, and narrow facies.

  
  
• 2.
  

  Cardiovascular involvement occurs in 50% by the age of 21 (see next section).

  
  
• 3.
  

  Eye manifestations may include lens subluxation, increased axial global length, myopia, and retinal detachment.

B

Cardiovascular Involvement

• 1.
  

  The CV abnormalities may include the following:

  
  
  
  
  • a.
    

    Dilatation of the sinus of Valsalva, dilatation of the ascending aorta, and AR are common.

    
    
  • b.
    

    Mitral valve abnormalities are more common than aortic lesions in children, including MR and MVP.

    
    
  • c.
    

    Aneurysm of the PA is less frequently seen.

    
    
  • d.
    

    Rarely, rupture of chordae tendineae, aneurysm of the abdominal aorta, and aneurysmal dilatation of the proximal coronary arteries may occur.

  
  
  
  
• 2.
  

  The ECG may show LVH; T-wave inversion in leads II and III, aVF, and left precordial leads; and first-degree AV block.

  
  
• 3.
  

  Chest radiographs may show a prominence of the ascending aorta, aortic knob, or main PA segment, and rarely cardiomegaly.

  
  
• 4.
  

  Echo studies show:

  
  
  
  
  • a.
    

    Increased dimension of the aortic root with or without AR.

    
    
  • b.
    

    “Redundant” mitral valve or MVP with thickened valve leaflets and MR.

    
    
  • c.
    

    In children, adult echo diagnostic criteria of MVP are rarely met, because MVP is a progressive disease. Systolic straightening or convex superior bowing of the leaflets or superior displacement of the mitral coaptation point may be an important sign of early MVP in this age group.

  
  
  
  
• 5.
  

  Early death is commonly precipitated by aortic dissection, chronic AR, or severe MR.

C

Management

Use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor blockers (ARBs) has significantly diminished the progression of aortic root dilatation, thus delaying surgical intervention. Timely and improved surgery has significantly increased the life expectancy of these patients in recent years.

• 1.
  

  Periodic examination of the aortic root dimension and the status of the MR and MVP is important.

  
  
• 2.
  

  β-Blockers (atenolol, propranolol) are effective in slowing the rate of aortic dilatation and reducing the development of aortic complications. In addition to traditional -blocker treatment, over the last decade, enalapril (an ACE inhibitor) and losartan (ARB) have been added to the medical regimen to treat dilated aortic root in Marfan syndrome patients. The role of prophylactic medical treatment in children with Marfan syndrome remains controversial; some physicians choose to start medications at the time of diagnosis of Marfan syndrome even without aortic root dilatation.

  
  
• 3.
  

  Discourage certain physical activities, such as weight lifting, rowing, push-ups, pull-ups, sit-ups, and hanging on a monkey bar, which may increase damage to the aortic root and aortic and mitral valves.

  
  
• 4.
  

  Surgery should be considered when the diameter of the aortic root increases significantly. However, there is controversy as to what is considered significant enlargement of the aortic root to require surgery. Current general recommendation for surgery is an aortic root diameter of ≥50 mm or rapid growth of more than 5 mm/year in Marfan patients. Normal two-dimensional (2D) echo dimensions of the aortic root and the aorta are presented in Table D.3 , in Appendix D .

  
  
• 5.
  

  Valve-sparing aortic root reconstruction appears to be preferable to composite graft surgery.

A

Description

• 1.
  

  In mucopolysaccharidoses (MPS), excessive amounts of glycosaminoglycans (previously called mucopolysaccharides) accumulate in various tissues, including the myocardium, cardiac valves, and coronary arteries. Hurler (type IH), Hunter (II), Scheie (IS), Sanfilippo (III), and Morquio (IV) are well-known eponyms.

  
  
• 2.
  

  A wide variety of clinical manifestations occur, including growth and mental retardation, skeletal abnormalities, clouded cornea, upper airway obstruction, and cardiac abnormalities (see following text).

  
  
• 3.
  

  In most cases the cause of death is cardiorespiratory failure secondary to cardiac involvement and upper airway obstruction.

B

Cardiac Manifestations

• 1.
  

  Echo studies show involvement of cardiac valves and myocardium.

  
  
  
  
  • a.
    

    MR is present in about 30% of the patients. It is more frequent in types IH (38%) than other types (24% in type II and 20% in type III). Thickening of the mitral valve is common.

    
    
  • b.
    

    AR is present in about 15% of the cases, often with thickened aortic valve. It is more common in type II (56%) and type IV (24%).

    
    
  • c.
    

    Myocardial abnormalities, such as asymmetric septal hypertrophy, hypertrophic cardiomyopathy, dilated cardiomyopathy, and endocardial thickening, are present in about 25% of the cases.

  
  
  
  
• 2.
  

  The ECG may show a prolonged QTc interval, RVH, LVH, or LAH.

  
  
• 3.
  

  Chest radiographs may show cardiomegaly in severe cases of valve regurgitation.

C

Management

Treatment depends on the abnormalities present.

A

Description

• 1.
  

  Duchenne muscular dystrophy (MD), a sex-linked recessive disease, involves the pelvic muscles and leads to lordosis, waddling gait, and difficulty rising.

  
  
• 2.
  

  Becker MD is the same fundamental disease as Duchenne MD, but it follows a milder and more protracted course.

B

Cardiac Involvement

• 1.
  

  Dilated cardiomyopathy is most common. MR and MVP may rarely develop.

  
  
• 2.
  

  The ECG abnormalities occur in 90% of the patients. RVH and RBBB are the most common abnormalities. Other abnormalities may include deep Q waves (in V5, V6), short PR interval, and T-wave inversion (in the limb leads or V5 and V6). Holter monitoring may show atrial tachycardia or frequent ventricular ectopies, especially in patients with low LV ejection fraction.

  
  
• 3.
  

  Echo studies show dilated cardiomyopathy in both Duchenne and Becker types. In early stages, only diastolic dysfunction (of reduced diastolic relaxation pattern) may be present. Systolic dysfunction appears later in the disease process. Cardiac magnetic resonance imaging (MRI) can quantify ventricular function as well as extent of myocardial fibrosis in patients with MD.

C

Management

• 1.
  

  Treatment is the same as that described for dilated cardiomyopathy (see Chapter 11 ).

  
  
• 2.
  

  Recent reports suggest ACE inhibitors (e.g., perindopril) may lead to improved LV function and possible delay of progression of the disease.

  
  
• 3.
  

  Addition of carvedilol (0.5 to 1 mg/kg, twice daily) may have additional benefits. Carvedilol may be added if average heart rate exceeds 100 beats/min (on a 24-hr Holter monitor).

A

Description

This autosomal dominant disease is characterized by myotonia (increased muscular irritability and contractility with decreased power of relaxation) combined with muscular weakness.

B

Cardiac Involvement

• 1.
  

  Involvement of the AV conduction and myocardial abnormalities are frequent (due to fatty infiltration).

  
  
• 2.
  

  The ECG may show first-degree AV block and intraventricular conduction delay. Second-degree and complete heart block may develop. In addition, atrial fibrillation and flutter and ventricular arrhythmias may develop.

  
  
• 3.
  

  Echo studies may show MVP and LV systolic dysfunction with advancing age.

  
  
• 4.
  

  Sudden death is frequent, attributable to conduction abnormalities and/or arrhythmias.

C

Management

• 1.
  

  Patients with symptoms or evidence of arrhythmias should be considered for antiarrhythmic agents and/or pacemaker treatment.

  
  
• 2.
  

  LV dysfunction, if present, should be treated.

A

Description

• 1.
  

  This autosomal dominant genetic disorder occurs in both males and females. Mutations in the PTPN11 gene located on chromosome 12 have been found in about 50% of the patients with Noonan syndrome. It was first described by Dr. Jacqueline A. Noonan, a pediatric cardiologist, in the early 1960s.

  
  
• 2.
  

  Characteristic findings include distinctive facial features (large head, wide-spaced eyes, epicanthal folds, low-set ears, and short and broad nose with depressed root), short webbed neck with low posterior hairline, cubitus valgus, chest deformity (pectus excavatum or carinatum), scoliosis, short stature, and CHD.

  
  
• 3.
  

  Although some clinical features are similar to Turner syndrome, patients with Noonan syndrome are often mentally retarded and normal sexual maturation usually occurs, although delayed.

B

Cardiovascular Abnormalities

• 1.
  

  Cardiovascular abnormalities are seen in more than 80% of the patients.

  
  
• 2.
  

  Pulmonary valve stenosis, often dysplastic, is the most common one (occurring in 25% to 35%). Secundum ASD is often associated with PS.

  
  
• 3.
  

  Hypertrophic cardiomyopathy is present in approximately 20% of patients.

C

Management

• 1.
  

  For significant PS, initial treatment is usually pulmonary balloon valvuloplasty, but it may be unsuccessful as the valve is at times extremely dysplastic. With severe dysplasia, a pulmonary valvectomy or pulmonary homograft may be needed in childhood.

  
  
• 2.
  

  Hypertrophic cardiomyopathy may be treated with β-blockers or surgical myomectomy.

  
  
• 3.
  

  Individuals without heart disease on their initial evaluation should be followed every 5 years because of possible late appearance of cardiac problems.

  
  
• 4.
  

  The patients should be followed by endocrinologists for possible need of growth hormone therapy, thyroid hormone replacement, or pubertal induction with estrogen (for females) or testosterone (for males).

A

Description

The synovium is the principal target of inappropriate immune attack in this condition. Irregular nodular thickening may be seen on cardiac valves (granulomatous valvulitis). Inflammatory cells may infiltrate the myocardium.

B

Cardiac Involvement

• 1.
  

  Pericarditis is the most common finding (occurring in about 50% of cases). It is most frequent in systemic-onset juvenile rheumatoid arthritis (JRA), occasionally in patients with polyarticular-onset JRA. Small pericardial effusion occurs without symptoms, but large effusion may cause chest pain.

  
  
• 2.
  

  Myocarditis occurs infrequently (1% to 10%) but can cause CHF and arrhythmias.

  
  
• 3.
  

  Rarely, MR and AR with thickening of these valves occur.

  
  
• 4.
  

  Occasionally, LV is dilated with systolic dysfunction.

  
  
• 5.
  

  The ECG may show nonspecific ST-T changes (in 20% of cases). Rarely, heart block can occur.

C

Management

• 1.
  

  Nonsteroidal antiinflammatory agents such as naproxen (15 mg/kg/day in 2 divided doses) may be used for mild pericarditis.

  
  
• 2.
  

  For symptomatic or severe pericarditis, corticosteroids are used. Prednisone 0.5 to 2 mg/kg/day (given TID or QID) for more than 1 week is gradually reduced by approximately 20% each week (given as a single dose).

  
  
• 3.
  

  Tamponade is treated with pericardiocentesis.

A

Description

• 1.
  

  Girls older than 8 years of age are most commonly affected (78%), with a female-to-male ratio of 6:1.

  
  
• 2.
  

  Varying degrees of immune-mediated changes occur in all layers of the heart: pericarditis, myocarditis, and classic verrucous Libman-Sacks lesion (on the cardiac valves).

B

Cardiovascular Manifestations

• 1.
  

  Pericarditis with pericardial effusion is the most common manifestation (occurring in about 25%) and is often asymptomatic.

  
  
• 2.
  

  Myocarditis occurs in 2% to 25%, with resting tachycardia.

  
  
• 3.
  

  Echo studies show the following:

  
  
  
  
  • a.
    

    Irregular vegetations, 2 to 4 mm in diameter (Libman-Sacks endocarditis), are seen most commonly on the mitral valve and less commonly on the aortic valve.

    
    
  • b.
    

    Diffuse thickening of the mitral or aortic valve (with or without regurgitation) is a more frequent finding than the verrucous lesion.

  
  

C

Management

1. If active valvulitis is suspected, corticosteroid therapy may be warranted.

2. Anticoagulation therapy should also be considered.

A

Description

• 1.
  

  Standard karyotyping shows 45,X (in more than 50%); others have a combination of monosomy X and normal cells (45,X/46,XX) (mosaic Turner syndrome).

  
  
• 2.
  

  Edema of the dorsa of the hands and feet and loose skin folds at the nape of the neck in a female neonate are characteristic.

  
  
• 3.
  

  In childhood, webbing of the neck, broad chest with wide-spaced nipples, cubitus valgus, and small stature are characteristic.

B

Cardiac Findings

• 1.
  

  Cardiovascular abnormalities are found in about 35% of the patients.

  
  
• 2.
  

  Bicuspid aortic valve (BAV), COA, and aortic wall abnormalities (ascending aortic dilatation, aneurysm formation, and aortic dissection) are more commonly found in patients with webbing of the neck.

  
  
• 3.
  

  Less common anomalies include elongated transverse arch, PAPVR involving the left upper PV (13%), and persistent left SVC (13%).

C

Management

• 1.
  

  Cardiac follow-up is required with attention to the following:

  
  
  
  
  • a.
    

    Aortic dimension should be determined on a regular basis (by MRI every 5 to 10 years). If the aorta is enlarged, treat it with β-blockers.

    
    
  • b.
    

    Monitor blood pressure (BP) for hypertension.

    
    
  • c.
    

    Exercise restriction. Highly competitive strenuous sports and isometric exercises are not recommended in patients with a dilated aortic root.

  
  
  
  
• 2.
  

  Follow-up by pediatric endocrinologists for the need of growth hormone and puberty induction with estrogen therapy.

  
  
• 3.
  

  Follow-up by an obstetrics and gynecology specialist because natural pregnancy occurs in 2% to 5% of the patients. Pregnancy carries a high risk because of possible aortic dissection during pregnancy and the postpartum period. History of surgically repaired CV defect, BAV, aortic dilatation, or systemic hypertension is relative contraindications of pregnancy.

A

Description

A microdeletion in the chromosomal region 7q11.23 near the elastin gene ( ELN ) is responsible. Elastin is protein that allows blood vessels and other tissues to stretch. Males and females are equally affected.

Patients with Williams syndrome have multisystem manifestations, including CV disease, developmental delay, learning disability, mental retardation, hearing loss, severe dental disease, ocular problems, nephrolithiasis, and bowel and bladder diverticula.

• 1.
  

  Many children have a history of failure to thrive, poor weight gain, colic, and delayed motor development during early life.

  
  
• 2.
  

  Most children with the syndrome have similar characteristic features. These features include a small upturned nose, long philtrum (upper lip length), wide mouth, full lips, small chin, a stellate pattern in the iris (seen in 50%), and puffiness around the eyes.

  
  
• 3.
  

  Affected children have personality trait of being very friendly, trusting strangers, fearing loud sounds, and being interested in music. They are also hyperactive, inattentive, easily distracted (attention deficit disorder).

  
  
• 4.
  

  Other findings include hoarse voice, joint hyperelasticity, contractures, kyphoscoliosis, and lordosis.

B

Cardiovascular Pathology

• 1.
  

  Elastin arteriopathy (with stenosis) most commonly affects the ascending aorta and the pulmonary arteries (supravalvular AS and PA stenosis), occurring singly or together in 55% to 80%.

  
  
• 2.
  

  Less common cardiac anomalies include COA, hypoplastic aortic arch, ASD, VSD, TOF, complete AV canal, and hypertrophic cardiomyopathy.

  
  
• 3.
  

  Systemic hypertension may be present or develop in approximately 50% of the patients.

  
  
• 4.
  

  High pressure in the sinus of Valsalva may lead to coronary ostial narrowing and coronary artery stenosis, resulting in increased risk for sudden death.

  
  
• 5.
  

  There may also be renal artery stenosis with resulting hypertension. Renal ultrasonography may find anatomic abnormalities (found in 15% to 20%) or nephrolithiasis (caused by hypercalcemia).

  
  
• 6.
  

  Hypercalcemia, which is noted in approximately 15% of infants with Williams syndrome, is frequently asymptomatic and resolves in the first few years of life but can be lifelong.

  
  
• 7.
  

  The ECG may show LVH in severe cases of supravalvar AS. BVH or RVH may be present with severe PA stenosis.

  
  
• 8.
  

  Sudden deaths with no apparent instigating event have been reported after the use of anesthesia, after sedation, or during invasive procedures (such as cardiac catheterization and heart surgery).

  
  
• 9.
  

  Higher frequency of prolonged QTc interval has been found in patients with the syndrome than in the control group; this has been raised as a possible cause of sudden death. Prolonged QTc interval (≥460 msec) is found in 13.6% of the patients (compared with 2.0% in controls). JTc prolongation (>340 msec) is found in 11.7% of the patients (compared with 1.8% in controls).

C

Management

• 1.
  

  Annual cardiology evaluation with assessment of the cardiac conditions, measurement of blood pressure, and check of the QTc interval.

  
  
• 2.
  

  Hypercalcemia should be treated, if present. Avoid taking extra calcium and vitamin D.

  
  
• 3.
  

  When planning a procedure, history should be evaluated carefully for syncope, angina, fatigue or dyspnea, and hemodynamic instability during previous anesthesia or sedation.

  
  
  
  
  • a.
    

    Avoid medications that are known to prolong the QTc interval.