The number of children now surviving surgical interventions because of congenital cardiac disease continues to increase. Indeed, it is estimated that, by the end of 2005, there will be more adults than children with congenital cardiac malformations. The complex challenges facing this growing population are only now becoming apparent, including the continued hazard for mortality, the risk of reoperation, and newly-emerging late sequels of surgery. In particular, children with severe lesions requiring intervention in the neonatal period are surviving at levels thought to be highly improbable no more than two decades ago. Heralded by the availability of prostaglandin E1 in the late 1970s, improvements in technology, such as echocardiography, and color Doppler in particular, intensive care and intraoperative support, have recently allowed surgeons to reconstruct the hearts of many children with otherwise lethal defects. Much of the published literature has focused on the cardiac sequels in this population. Increasing attention has recently been given, nonetheless, to the neurodevelopmental outcomes in this population of patients.

The DiGeorge, or velocardiofacial, syndrome has been aetiologically linked to heterozygous deletion of the q11.2 region of chromosome 22. It is the most common of the microdeletion syndromes, and is associated with malformations involving the ventricular outflow tracts. Duplication of the 22q11.2 region has also been reported, adding to a growing list of syndromes involving genomic deletion or duplication that cause disease by decreasing or increasing the gene dosage. We report two cases of congenital cardiac disease associated with microduplications of 22q11.2, and discuss the evidence to date for the potential clinical significance of this genetic defect.

As the overall mortality declines following repair of complex congenital cardiac malformations, attention has focused on reducing the lasting morbidity of these interventions, particularly the observed neurodevelopmental deficiencies. Both cardiopulmonary bypass and deep hypothermic circulatory arrest produce transient alterations in cerebral hemodynamics and metabolism. In studies performed in animals, deep hypothermic circulatory arrest, as compared to cardiopulmonary bypass alone, has been shown to produce excess injury to, and death of, neuronal and glial cells.1 In neonates, deep hypothermic circulatory arrest of greater duration than one hour is a risk factor for early post-operative seizures, and for subsequent neurodevelopmental deficits.2 The Boston Circulatory Arrest Study suggests that, at follow-up of eight years, infants subjected to greater than 41 minutes of deep hypothermic circulatory arrest had excess deficits in full-scale, verbal and performance intelligence quotient, the Mayo apraxia test, and grooved pegboard testing.3 The independent adverse effects of deep hypothermic circulatory arrest have encouraged clinicians to develop the alternative technique of intermittent global perfusion, or continuous regional perfusion at low flow perfusion, in an attempt to reduce the degree of injury to the central nervous system.4–7

The evolution of cardiac surgery has led to increasing emphasis on complete repair of congenital heart defects early in life, nowadays increasingly performed in neonates or small infants. Good results have been achieved because of innovative techniques permitting reconstruction of normal anatomy, and restoration of normal physiology, before either the heart or the patient undergo deleterious adaptation to the congenitally abnormal physiology. Despite the ability surgically to correct complex defects in such small patients, limitations in outcome are sometimes encountered related to the systems necessary for repair. In particular, exposure to cardiopulmonary bypass may present the greatest challenge for these tiny patients.

Survivors of repairs of complex congenital cardiac malformations in infancy have an increased risk of permanent abnormalities in motor, cognitive, expressive, and behavioral functioning. These functional deficits are expressions of complex interactions of environment, including prolonged hospitalization and conditioned child–parental behaviours, alterations of social environment, the effects of physical limitations, biological influences including genetic determinants, prenatal injury, and acquired reversible and irreversible neuronal injury.1,2 The magnitude of the problem is large, with incidence dependent upon the measures used for assessment. Overt postoperative neurologic signs have been recorded in up to one-tenth of postoperative infants and children, with double that rate found in those with abnormalities of the aortic arch.3 A decreased potential for development, based upon parent-sibling models, has been estimated to occur in one-third of survivors.4,5 Evidence of injury is provided by magnetic resonance imaging in up to one-third of patients preoperatively, and between half and nine-tenths postoperatively, although most of these early postoperative changes will disappear.5 Although recent changes in perioperative management are likely to reduce such neurologic injury, their significance remains high.