Infants and children with genetic syndromes frequently have associated cardiovascular abnormalities. It is important to recognize the cardiovascular anomalies associated with these genetic syndromes, as they account for significant morbidity and mortality. In this chapter, important genetic syndromes that are associated with cardiovascular manifestations are presented successively and include:

• Down syndrome.

• Turner syndrome.

• DiGeorge syndrome.

• Williams syndrome.

• Marfan syndrome.

The focus of this chapter is on the cardiovascular abnormalities. For further clinical information on these genetic syndromes, please refer to Chapters 216, DiGeorge Syndrome; 221, Down Syndrome; 222 Turner Syndrome; and 223, Marfan Syndrome.

Patient story

A 35-week premature infant of a 42-year-old mother is delivered due to premature labor. A prior fetal echocardiogram showed an atrio-ventricular (AV) canal defect. The patient’s mother had denied amniocentesis and chromosomal testing during pregnancy. Post-natal examination of the infant reveals simian creases, macroglossia and sandal gap toe. The diagnosis of Down syndrome is made clinically and the diagnosis of AV canal defect is confirmed on echocardiogram (Figure 47-1). Surgery to repair the AV canal defect was scheduled at 3 to 6 months of age.

Introduction

Down syndrome (Trisomy 21) is associated with a significant risk of congenital heart disease. Every infant with Down syndrome must be evaluated for the presence of congenital heart disease.

Synonyms

Trisomy 21

Epidemiology

• Cardiovascular malformations are found in 40 to 50 percent of individuals with Down syndrome.¹

Etiology and Pathophysiology

• A spectrum of endocardial cushion defects is common in Down syndrome and its prevalence is higher in patients with Down syndrome compared to that of general population.

• The most common cardiac anomalies associated with Down syndrome include common AV canal, ventricular septal defect (VSD), tetralogy of Fallot and patent ductus arteriosus.

Risk factors

• Advanced maternal age.

Diagnosis

• The diagnosis of Down syndrome is frequently made antenatally with first trimester screening lab tests and ultrasound appearance of increased nuchal cord thickness.

• Diagnosis is often confirmed by chromosomal analysis from amniocentesis.

• Antenatal diagnosis of cardiac defects in Down syndrome fetuses is accomplished by fetal echocardiography in the second trimester.

• Newborn infants with AV canal defects are typically asymptomatic. They typically manifest symptoms at 3 to 6 months of age when the pulmonary vascular resistance decreases.

Imaging

• Electrocardiogram should be obtained and will reveal abnormalities associated with the specific cardiac defects (Figure 47-2).

• Echocardiography.

Management

• Management of each cardiac lesion in Down syndrome is addressed in Chapter 42, Acyanotic Congenital Heart Disease, and Chapter 43, Cyanotic Congenital Heart Disease.

Referral

• Many of the cardiac defects are detected by antenatal screening ultrasounds and appropriate referral to a fetal cardiologist for further evaluation with a fetal echocardiogram is commonplace.

Prevention and Screening

• Screening for a cardiac anomaly is usually performed by prenatal ultrasounds in the second trimester.

Prognosis

• The prognosis depends on the specific cardiac anomaly detected.

Follow-up

• Once a cardiac anomaly is detected prenatally or postnatally, careful follow-up by a pediatric cardiologist is required.

Patient story

A 16-year-old female is seen by her primary care physician for primary amenorrhea. On examination she is noted to have short stature, a webbed neck, and widely spaced nipples. Her upper limb blood pressures are above the 95th percentile for her height and four-extremity blood pressures show a systolic gradient of 50 mm Hg between the upper and lower limbs. She has brachiofemoral delay. On chest auscultation she has a grade II/VI systolic ejection murmur in the base of the heart and in the left interscapular region. She also has a continuous murmur audible almost all over the rib cage. A diagnosis of coarctation of the aorta is made via echocardiography and CT angiography (Figure 47-3). Chromosomal testing confirms the diagnosis of Turner syndrome. She undergoes surgical repair of the coarctation without complications.

Introduction

Turner syndrome is caused by an absence of one sex chromosome yielding the 45,X genotype. Turner syndrome is associated with coarctation of the aorta.

Synonyms

45X syndrome, Bonnevie-Ullrich syndrome, Monosomy X, Ullrich-Turner syndrome.

Epidemiology

• The incidence of Turner syndrome is approximately 1 in 2000 liveborn female infants²

• Twenty to 40 percent of girls born with Turner syndrome have cardiovascular anomalies.

Etiology and Pathophysiology

• The most common cardiovascular malformation is coarctation of the aorta, although bicuspid aortic valve and aortic stenosis are also common.

• Patients with Turner syndrome can have a spectrum of left heart obstructive lesions ranging from bicuspid aortic valve to hypoplastic left heart syndrome, although the latter is quite rare.

Diagnosis

• Unlike Down syndrome, Turner syndrome is usually diagnosed postnatally. Once the diagnosis of Turner syndrome is made, a clinical and echocardiographic evaluation for cardiac defects should be performed.

• Complete or near complete obstruction occurring from coarctation of the aorta can result in left sided heart failure.

• Milder forms of coarctation may go unnoticed for many years and become apparent during evaluation of “primary” hypertension.

• As described in the case, uncomplicated coarctation of the aorta will have clinical signs of hypertension, lower blood pressures in the lower limbs, brachiofemoral delay and a systolic ejection murmur in the left interscapular region.

• A long-standing coarctation can cause collateral flow through the intercostal arteries resulting in continuous murmurs.

• Patients with a bicuspid aortic valve can have a systolic click and/or a systolic ejection murmur in the aortic area radiating to the carotid arteries.

Imaging

• A chest radiograph can show rib notching due to collateral artery formation in aortic coarctation. This finding is uncommon in young children.

• An echocardiogram offers definitive diagnosis of the cardiac manifestations, although MRI and CT angiography may be utilized to help demonstrate the level of the obstruction, especially in older patients.

Differential Diagnosis

• Associated left-sided cardiac anomalies should be excluded when a coarctation is diagnosed in a patient with Turner syndrome.

Management

• The mainstay of management is surgical repair of aortic coarctation.³ SOR A

• Balloon angioplasty or stent placement can also be used in select patient groups. ⁴ SOR B

Referral

• All patients with Turner syndrome should have evaluation performed by a pediatric cardiologist.

Prognosis

• The prognosis is excellent following successful complete surgical repair.

• Sports participation is generally permitted with the exception of high static (isometric) activities.⁶ SOR B

• Systolic blood pressures should be monitored closely after coarctation repair, as hypertension may develop.

Follow-up

• Depending on the diagnosis and timing of repair, close follow-up with a pediatric cardiologist is required to look for a recurrence or for development of complications such as hypertension.

Patient Education

• A collaborative approach of management in this patient group involving a geneticist, pediatric endocrinologist and general pediatrician should be planned and patients should be provided with anticipatory information regarding prognosis and follow-up.