IJCS | Volume 33, Nº4, July and August 2020

424 Table 1 - Frequency of clinical features in patients with 22q11.2DS Clinical features Frequency Abnormal ears 45% Hypoplastic alae nasi 29.40% Long face 41% High nasal bridge 19.60% Broad nasal root/nose 24% Micro/retrognathia 47.70% Epicanthic folds 19% Malar flattening 32% Long digits 68.30% Narrow palpebral fissures 73.20% Hypoplastic face 34% Speech delay 76.40% Learning disabilities 75% Behavioral disturbances 72.50% Palatal abnormality 66.00% Congenital heart disease 64.60% Ventricular septal defect 35.8% Atrial septal defect 28.3% Tetralogy of Fallot 20.0% Pulmonary atresia/stenosis 11.3% Persistent truncus arteriosus 5.6% Santos et al. Congenial heart disease and 22q11 deletion Int J Cardiovasc Sci. 2020; 33(4):423-428 Case Report structural malformations that are similar to ventricular outflow tract defects. These include the Tetralogy of Fallot (TOF), pulmonary atresia with ventricular septal defect (PA-VSD), a double outlet right ventricle, transposition of the great arteries, persistent truncus arteriosus, and an interrupted aortic arch. 3 Low-copy repeats (LCRs) of 22q11 have been suggested to mediate a non-allelic homologous recombination, resulting in 22q rearrangement. An unequal crossover between the LCRs usually results in a 3mebabase (Mb) deletion in one copy of chromosome 22, and a reciprocal and similarly sized duplication in the other one. 4 A microscopic deletion at 22q11 occurs in approximately 1 out every 4,000 live births. Different deletion genotypes have been delineated to this condition: a predominant 3-Mb deletion accounting for 90% of the cases, a 1.5–2-Mb deletion in 8%, and atypical smaller deletions in 2%. Phenotypic variability has been attributed to the presence or absence of genes in the breaking points, and CNVs depending on the size of the deletion. 5 Familial cases of 22q11DS present a higher frequency of uncommon 1.5–2 Mb deletions; 6 patients with this deletion have symptoms that are indistinguishable from those seen in patients with larger deletions, indicating that this region may be fundamental to the phenotype. 7-10 Here we describe the cases of three children who were referred to our hospital with diagnoses of heart disease and no signs of 22q11DS, which turned out to be familial cases of 22q11DS. Clinical reports This study was approved by the ethics committee of the Federal University of Goiás inGoiania, Brazil. Written informed consent were obtained fromall familymembers included in the study. Proband 1 was a 16-month-old girl born via cesarean section at term. The parents were nonconsanguineous, including a 23-year-old gravida 1, para 1 (G1P1) mother and a 27-year-old father. Her birth weight was 3,280 g (25–50 th percentile), length was 46 cm (3 rd percentile), and occipital frontal head circumference (OFC) was 35 cm (> 50 th percentile). A clinical examination at the age of 16 months showed a round face, narrow forehead, TOF, and normal development. Clinical examination of the mother revealed a long face, mid-face hypoplasia, retrognathia, slender hands and digits, long toes, hypernasal speech, a speech delay, and a learning disability. The clinical examination of her grandmother showed epicanthic folds, retrognathia, normal development, and a surgically corrected cleft palate. Further information from the family also revealed an individual who died at birth due to heart disease (Figure 1A1). Pictures of this family were not allowed for publication. Proband 2 was a 19-month-old boy who was born via cesarean section at term. The parents were nonconsanguineous, including a 26-year-old G1P1 mother and a 29-year-old father. His birth weight was 3,360 g (25–50 th percentile), length was 47 cm (3 rd percentile), and OFC was 35 cm (> 50 th percentile). Clinical examination at 19 months of age showed interventricular communicationandnormal development, with no further clinical features. Clinical examination of hismother revealed a long face, small mouth, dysmorphic