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Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling. [ABSTRACT FROM AUTHOR]

Congenital anomalies (CA) affect 3–5% of newborns, representing the second-leading cause of infant mortality in Argentina. Multiple congenital anomalies (MCA) have a prevalence of 2.26/1000 births in newborns, while congenital heart diseases (CHD) are the most frequent CA with a prevalence of 4.06/1000 births. The aim of this study was to identify the genetic causes in Argentinian patients with MCA and isolated CHD. We recruited 366 patients (172 with MCA and 194 with isolated CHD) born between June 2015 and August 2019 at public hospitals. DNA from peripheral blood was obtained from all patients, while karyotyping was performed in patients with MCA. Samples from patients presenting conotruncal CHD or DiGeorge phenotype (n = 137) were studied using MLPA. Ninety-three samples were studied by array-CGH and 18 by targeted or exome next-generation sequencing (NGS). A total of 240 patients were successfully studied using at least one technique. Cytogenetic abnormalities were observed in 13 patients, while 18 had clinically relevant imbalances detected by array-CGH. After MLPA, 26 patients presented 22q11 deletions or duplications and one presented a TBX1 gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in KAT6B, SHH, MYH11, MYH7 and EP300 genes, are novel. Using an algorithm that combines molecular techniques with clinical and genetic assessment, we determined the genetic contribution in 27.5% of the analyzed patients. [ABSTRACT FROM AUTHOR]

Introduction: Critical congenital heart disease (CCHD) is a term that refers to ductus-dependent structural anomalies of the heart that may be fatal or require invasive management in the first month of life., Objective: To know the prevalence and distribution of CCHD among newborns in Argentina, compared to other countries, and the proportion of prenatal detection and perinatal mortality., Material and Methods: Data provided by the National Network of Congenital Anomalies (Red Nacional de Anomalías Congénitas de Argentina, RENAC) for the 2009-2018 period and by other surveillance systems in the United States, Europe, and Colombia were used. For Argentina, the proportion of prenatal detection, perinatal mortality, and CCHD prevalence in newborns by jurisdiction and health system subsector were analyzed., Results: The prevalence of CCHD was 11.46 (95% confidence interval: 11.02-11.92) every 10 000 births. Prenatal detection was possible in 43.93% of cases, and perinatal mortality was 25%. Tetralogy of Fallot was the most frequent specific defect. The prevalence of CCHD and percentage of prenatal detection was significantly lower in the public subsector, whereas perinatal mortality was higher in this subsector. The prevalence of CCHD was lower than in the United States (NBDPN) and European (EUROCAT) registries. The Bogotá Registry showed different specific prevalence values., Conclusion: The prevalence of CCHD is lower than what has been observed in other countries, and even lower in the public sector of Argentina. The need to improve prenatal detection and implement pulse oximetry among newborns as a mandatory and universal screening is emphasized.

Kabuki syndrome is a genetic entity with multiple anomalies associated with intellectual disability. The clinical diagnosis is based on typical facial features, minor skeletal abnormalities, finger pads, and postnatal growth deficit. Other findings may include congenital heart disease, genitourinary anomalies, oral clefts, anal atresia, increased susceptibility to infections, autoimmune and endocrine disease and hearing loss. The objective of this paper is to describe two patients with clinical diagnosis of Kabuki syndrome, highlighting the phenotypic findings and associated malformations.