Congenital anomalies (CA) are morphological and/or functional disorders that originate before birth. Affecting 3 to 5 % of newborns, they represent the second leading cause of infant mortality in Argentina, after perinatal conditions. In approximately 50% of the patients, the underlying causes are unknown. Cases with MCA are those with 2 or more unrelated birth defects. MCA are present in 2,26/1000 births. CHD are the most frequent CA, with a prevalence of 4,06/1000 births. The goal of this work was to identify the genetic causes of MCA and isolated
CHD cases from our population. We studied 275 patients (150 MCA and 93 isolated CHD) born between June 2015 and January 2017 in 13 public hospitals participating in the National Network of Congenital Anomalies of Argentina (RENAC). Peripheral blood and DNA was obtained from all patients and a karyotype was performed in MCA patients. Patients with conotruncal CHD (cCHD, n=69) were studied by MLPA. Array-CGH was performed in 30 MCA selected patients. Eighty MCA patients displayed a normal karyotype, 10/127 presented cytogenetic
abnormalities: a trisomy 13, 5 trisomy 18, a 47,XXX/47,XX,+14, a (t(1;2)(q25;q21)), a t(11;17)(p10;p10) and 1 supernumerary marker chromosome. The karyotype could not be performed in 27 patients due to culture failure. These results are in accordance with the expected frequency of chromosomal abnormalities. Among 69 cCHD patients, 12 presented a typical 22q11 deletion, 3 22q11 short deletion, one 15q14 duplication and one TBX1 gene deletion. Our 22q deletion frequency (0,22) is slightly higher than reported for cCHD. By array-CGH, we identified 2 trisomies, 14 CNVs (copy number variants):8 pathogenic in 7 patients, 1 likely pathogenic, 1VUS (variants of uncertain significance), 3 likely benign in 1 patients and 1 benign CNVs. The diagnostic yield of array- CGH was 21%. With the combine algorithm performed, we determined a causative genetic cause in 34 patients.