Pediatric Atrial Septal Defects Clinical Presentation
- Author: Michael R Carr, MD; Chief Editor: P Syamasundar Rao, MD more...
Infants and young children with atrial septal defects (ASDs) are typically asymptomatic. Most atrial septal defects are diagnosed after a suspicious murmur is detected during a routine health-maintenance examination.
Even in symptomatic children with atrial septal defects, clinical manifestations are often subtle and nonspecific. Some children with atrial septal defects have poor weight gain, they remain somewhat small, and they may have exertional dyspnea or frequent upper respiratory tract infections.
Relatively severe symptoms, such as arrhythmia, pulmonary artery hypertension, and pulmonary vascular obstructive disease (PVOD), are rare in children with atrial septal defects. Some infants and young children with large defects may present with symptoms of congestive heart failure (CHF), especially if they have an associated lesion (eg, patent ductus arteriosus) or lung disease (eg, bronchopulmonary dysplasia and/or chronic lung disease).
Most children with atrial septal defects are asymptomatic. In developed countries, the diagnosis is usually made during an evaluation of a suspicious murmur or during an evaluation of fatigue and exercise intolerance. Atrial septal defects that are not diagnosed in childhood can result in problems in adulthood.
Upon initial evaluation, many children with atrial septal defects appear completely healthy; however, careful physical examination often yields clues to the diagnosis.
Patients with atrial septal defects may have a precordial bulge, a prominent right ventricular cardiac impulse, and palpable pulmonary artery pulsations. All of these are signs of increased blood flow through the right side of the heart and pulmonary vascular bed.
Upon auscultation of the individual with atrial septal defect, the first heart sound may be normal or split. The sound associated with closure of the tricuspid valve may be accentuated if blood flow across the pulmonic valve is increased and leads to a midsystolic pulmonary ejection murmur. This sound is best appreciated at the upper left sternal border and may be transmitted to the lung fields.
Although the second heart sound may be normal in newborns with atrial septal defects, it becomes widely split and fixed over time as pressures on the right side of the heart decrease. This fixed splitting occurs as the result of increased capacitance in the pulmonary vascular bed, leading to low pulmonary impedance and, therefore, a long hangout interval after the end of right ventricular systole. Fixed splitting of S2 is an important diagnostic finding in atrial-level shunting.
A large shunt increases flow across the tricuspid valve, and the patient with atrial septal defect is likely to have a mid-diastolic rumble at the left sternal border.
Mitral valve prolapse occurs with increased frequency in the presence of atrial septal defect and may be caused by compression of the left side of the heart secondary to enlargement of the right side. In patients with mitral valve prolapse, an apical holosystolic or late systolic murmur often is heard radiating to the axilla. A midsystolic click may be present, but this murmur can be difficult to detect in some patients with atrial septal defects.
Pulmonary vascular resistance (PVR) may increase through childhood, adolescence, and adulthood, resulting in PVOD. The rise in PVR and pulmonary artery pressure results in right ventricular hypertrophy, which, in turn, reduces right ventricular compliance and may subsequently reduce the degree of left-to-right shunting.
Upon physical examination, patients may have a prominent right ventricular impulse, but the previously noted diastolic tricuspid flow rumble and the systolic ejection murmur in the pulmonic area may be diminished. The wide splitting of the second heart sound may narrow, and the pulmonic component of the second heart sound may become loud, with intensity equal to that of the aortic component.
In all patients with common atrium, right-to-left shunting occurs, resulting in cyanosis, although this may be mild due to preferential streaming of blood across the respective atrioventricular (AV) valves.
In adults with an unrecognized atrial septal defect, the left-to-right shunt may worsen if systemic arterial hypertension develops. The result may be left ventricular hypertrophy, reduced left ventricular compliance, and increased left-to-right shunt.
Although many cases of atrial septal defect are sporadic, atrial septal defect clearly has a genetic component and may be associated with genetic syndromes.[3, 4]
Ostium secundum atrial septal defect is typically a part of the Holt-Oram syndrome, which is caused by mutations in the T-box transcription factor TBX5 on chromosome 12q. Most of the mutations are deletions, frameshifts, or premature stop codons. This autosomal dominant and highly penetrant disease also includes absent or hypoplastic radii and first-degree heart block.
Ostium secundum atrial septal defect can also be associated with the following genetic abnormalities: Ellis-van Creveld syndrome, Noonan syndrome, Rubinstein-Taybi syndrome, Kabuki syndrome, Williams syndrome, Goldenhar syndrome, and thrombocytopenia-absent radius syndrome, as well as chromosomal abnormalities (eg, deletions in 1, 4, 4p, 5p, 6, 10p 11, 13, 17, 18, 22) or in trisomy 18 and Klinefelter syndrome. Ellis-van Creveld syndrome can be associated with a common atrium.
Ostium secundum, ostium primum atrial septal defect, or both may occur in trisomy 21 (Down syndrome). For unknown reasons, sinus venosus defects are rare in Down syndrome, making common atrium similarly rare in this population.
An autosomal dominant form of familial atrial septal defects with incomplete penetrance has been detected.
Mutations in NKX2.5, a homeodomain-containing transcription factor, have been associated with atrial septal defects with and without AV block and was the first gene identified leading to nonsyndromic atrial septal defect. To date, more than 40 NKX2.5 mutations have been detected. Interestingly, the type and location of the mutation predicts the phenotype, with nonsense mutations, frameshift mutations, and all mutations located in the homeodomain causing AV conduction disease, and missense mutations outside the homeodomain show no AV conduction disease.
Mutations in GATA4, an important regulator of cardiac development, have been associated with atrial septal defects. Interactions between GATA4 and NKX2.5 and interactions between GATA4 and TBX5 may be the root of the cardiac defects seen with GATA4 mutations, which establishes a link among these genes.[6, 8]
TBX20, a member of the TBX transcription factor family, is very highly expressed in the embryonic heart and also interacts extensively with NKX2.5, GATA4 and TBX5 during cardiac embryogenesis. It has been speculated that it may have a role in defects of the atrial septum.
Interestingly, a missense mutation in myosin heavy chain 6 (MHY6) has also been identified with an autosomal dominant form of atrial septal defect. MHY6 was previously described in late-onset hypertrophic cardiomyopathy. This gene is highly expressed in the developing atria and appears to be influenced by TBX5 and GATA4 mutations, again establishing a link between several genes. In a recent study by Posch et al, 3 novel missense mutations were found in MYH6 and no other mutations were identified in 11 other sarcomeric genes analyzed, leading the authors to conclude that MYH6 was the predominant sarcomeric disease gene for familial atrial septal defect.[6, 9]
The prognostic implications of the involvement of a sarcomeric protein with atrial septal defects has yet to be fully elucidated but suggest that sarcomeric filaments play a role in cardiac morphogenesis and atrial septal development. Further genetic analysis will likely yield other mutations and genetic links associated with familial atrial septal defects.
Atrial septal defects have been linked to maternal disease and exposure to environmental risk factors during pregnancy. Maternal diseases include phenylketonuria, pregestational diabetes, methylenetetrahydrofolate reductase deficiency (MTHFR deficiency), febrile illnesses, and influenza. Environmental risk factors include medications such as anticonvulsants and nonsteroidal anti-inflammatory drugs (NSAIDs) or exposure to organic solvents. Atrial septal defects are also found in children with fetal alcohol syndrome.
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