Cardiac aspects of DiGeorge syndrome : a report of two cases with molecular analysis

© 2014 Senka Mesihoviæ Dinareviæ, Emina Vukas; licensee University of Sarajevo Faculty of Health Studies. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES ABSTRACT


INTRODUCTION
Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the fi rst year of life with a prevalence of 1% in live births and 10% in spontaneously aborted fetuses (1). CHD is a disorder mainly characterized by: a) 90% multifactor disorders, b) 8% chromosomal and single gene disorders and c) 2% environmental teratogens (2). Among chromosomal disorders is DiGeorge syndrome (DGS) which is also known as velocardiofacial syndrome, caused by a submicro-scopic chromosome deletion of band 22q11. It has malformations attributed to abnormal development of the pharyngeal arches and pouches. Th e common thread among all the organs involved in DiGeorge anomaly is that their development depends on migration of neural crest cells to the region of pharyngeal pouches. Clinical features of this syndrome are: congenital cardiac defects, congenital immunodefi ciency secondary to aplasia or hypoplasia of the thymus, and hypocalcaemia due to small or absent parathyroid glands, cognitive, behavioral, and psychiatric problems and increased susceptibility to infections (3,4). One of the most widely cited article estimated that prevalence rate for DiGeorge syndrome is approximately 1 in 4,000 live births (5,6 A seven days old male newborn was admitted in local hospital in a state of circulatory shock, cardio respiratory decompensated, in severe metabolic acidosis. After condition has stabilized (intubation, complete  (Figure  1.), only by the FISH analysis ( Figure 2).

DISCUSSION
Approximately 75-80% of patients with DGS have congenital heart disease with conotruncal and ventricular septal defects. Various cardial malformations are seen, particularly aff ecting the outfl ow tract (6). In a series of 545 patients with 22q11 deletions (7), only 20% had no cardiac defects (ie, based on clinical examination and echocardiography fi ndings). Th e most common cardiac anomalies included Te-

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tralogy of Fallot (17%), ventricular septal defect and interrupted aortic arch (14% each), pulmonary atresia/ventricular septal defect (10%), and truncus arteriosus (9%), other anomalies included pulmonic stenosis, atrial septal defect, atrioventricular septal defect, and transposition of the great arteries. Th ymic hypoplasia/aplasia, palate defects and thyroid and parathyroid abnormalities were described as well. A congenital heart defect is the main cause of morbidity and mortality, but the underlying molecular pathobiology is not well understood. Mortality rate was 8% in a study with 558 patients (7). Most deaths in this study occurred within 6 months after birth. Infections due to severe immune defi ciency are the second most common cause of mortality. According to the current literature, in patients with Tetralogy of Fallot with/without pulmonary atresia and truncus arteriosus, in spite of the complex cardiac anatomy, the presence of 22q11.2 deletion syndrome does not worsen the surgical prognosis. On the contrary in children with pulmonary atresia with ventricular septal defect and in those with interrupted aortic arch the association with 22q11.2 deletion syndrome is probably a risk factor for the operative treatment (8).
In both our patients we had good postoperative outcome, although it was a complex CHD (Tetralogia Fallot and Interruption aortic arch). Th e complex cardiovascular anatomy in association with depressed immunological status, pulmonary vascular reactivity, neonatal hypocalcemia, bronchomalacia and broncospasm, laryngeal web, and tendency to airway bleeding must be considered at the time of diagnosis and surgical correction. Specifi c diagnostic, surgical, and perioperative protocols should be applied in order to provide appropriate treatment and reduce surgical mortality and morbidity (8).
As for its diagnosis, high-resolution karyotyping has limitations and is able to identify less than 15% of aff ected patients. Fluorescence in situ hybridization (FISH), which can detect over 90% of the cases, is considered the gold standard (9). Th e wide availability of commercial FISH probes has enhanced the clinicians' ability to diagnose and treat the affected children rapidly (10). Identifi cation of these patients is essential for their adequate management and genetic counseling.

CONCLUSION
Our report suggests that the criteria in searching for microdeletion 22q11.2 should be expanded and applied in patients with conotruncal and nonconotruncal congenital heart defects and at least one typical feature of this syndrome (facial dysmorphy, thymus hypoplasia/aplasia, cleft palate or hypocalcaemia). Th e phenotype can be extremely variable, frequently leading to clinical confusion, diagnostic delay, excess morbidity, early mortality. A multidisciplinary approach is fundamental to ensure that the patient will be able to attain his or her maximal potential.

COMPETING INTERESTS
Th e authors declare that they have no competing interests.