IJCS | Volume 33, Nº4, July and August 2020

DOI: https://doi.org/10.36660/ijcs.20180060 423 CASE REPORT International Journal of Cardiovascular Sciences. 2020; 33(4):423-428 Mailing Address: Bruno Gamba Avenida Esperança, S/N. Postal Code: 74001-970, Goiânia, Goiás, GO - Brazil. E-mail: gamba.bf@hotmail.com Congenital Heart Disease Revealing Familial 22q11 Deletion Syndrome MarleneViviane Pires Fernandes Santos, 1 B runo Faulin Gamba, 1 S tefany Lucas Lopes Empke, 2 C amila Cristina de Oliveira Alves, 2 N ádia Aparecida Bérgamo, 1 L ucilene Arilho Ribeiro-Bicudo 1 Universidade Federal de Goiás - Campus Samambaia, 1 Goiás, GO - Brazil Universidade Estadual Paulista - Campus de Botucatu, 2 São Paulo, SP - Brazil Manuscript received on July 26, 2018, revised manuscript on September 20, 2018, accepted on February 27, 2019. Congenital Heart Disease/genetics; Face/abnormalities/ genetics; DiGeorge Syndrome/genetics; Chromosomes, Human, Pair 22/genetics; Chromosome Deletion. Keywords Abstract Congenital heart defects are the most common birth defects and the leading cause of mortality in the first year of life. It is well known that the 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and that congenial heart diseases (CHDs) are one of the most common phenotypic manifestations. However, it should be noted that the 22q11 deletion was also found in a significant number of patients with isolated CHD. The 22q11DS phenotypemay include cardiovascular anomalies, palatal abnormalities, nasal voice, immune deficiency, endocrine dysfunctions, a varying degree of cognitive deficits and intellectual disabilities, velopharyngeal insufficiency, and characteristic craniofacial dysmorphism. This condition affects about 1 in 4,000 live births, making 22q11DS the most common microdeletion syndrome in humans. Here we describe the cases of three children who were referred to the clinical hospital center with the diagnosis of CHD, but with no direct signs of 22q11DS. Investigation of familial data led us to suspect that the mothers could be carriers of 22q11DS. The multiplex ligation-dependent probe amplification (MLPA) testing confirmed that the patients and mothers exhibited 3 Mb 22q11 deletions, which justified the clinical signs in the mothers and the CHD in children. In the presence of a few characteristics that are common of a spectrum of some known syndromes, a familial examination can provide clues to a definitive diagnosis, as well as to the prevention of diseases and genetic counseling of these patients. Introduction Congenital heart defects (CHDs) are themost common group of birth defects in humans that arise during cardiac embryogenesis and differ in morphology, physiology, and clinical outcome. They occur in about 1% of all live births irrespective of ethnic backgrounds, socioeconomic conditions, and geographic barriers. 1 The causes of CHDs are multiple, and typically categorized in genetic and nongenetic factors. Nongenetic factors include teratogenic exposures during pregnancy and epigenetic alterations. Identifiable genetic etiologies are reported to be as high as 40% in syndromic CHD, including single gene disorders, chromosomal anomalies, and copy number variations (CNV). 2 The 22q11.2 deletion syndrome (22q11DS; Online Mendelian Inheritance in Man #602054) is the most frequent microdeletion syndrome, and is one of the most common genetic causes of CHD, responsible for 1.5% to 5% of all CHD at birth. 3 This genetic disorder affects pharyngeal and neurobehavioral development, and causes congenital heart defects, velopharyngeal insufficiency, hypoparathyroidism, thymic aplasia or hypoplasia, craniofacial dysmorphism, learning difficulties, and psychiatric disorders. 1 Combination of these signs differ from patient to patient, resulting in a large number of phenotypes ranging from normal to severely handicapped individuals. 2 The frequency of clinical signs was previously reported by our group in a study involving 179 patients with 22q11DS confirmed by genetic tests (Table 1). Usually, 15–20% of the CHDs are conotruncal heart defects (CTDs). CTDs are more commonly associated with 22q11DS and comprise