Riassunto analitico
ABSTRACT
Purpose:
Mowat–Wilson syndrome (MWS; OMIM# 235730) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. Despite CHD are one of the most important features of MWS, to date no studies have been carried out with the aim of study cardiovascular findings.
Methods:
Through genetic analysis (FISH, ARRAY CGH, Multiplex PCR), we delineated three main mutational groups ( A - full gene deletion, B - protein absence, C- defective protein) in 83 MWS patients with a proven ZEB2 defect, compared it with data identified in a thorough review of literature published cases, and evaluated genotype–phenotype correlations.
Results:
Fifty-nine percent of our patients presented almost one congenital heart disease. The most common heart defects were PDA (29.6% of cases), VSD (26.3%), ASD (25.9%), and pulmonary stenosis (18.5%). Other consistent findings were Aortic coarctation, Aortic valve stenosis, Bicuspid aortic valve, Tetralogy Fallot, Peripheral pulmonary artery stenosis, Pulmonary artery sling, Pulmonary atresia and Mitral Prolaps. Meanwhile no cases of Missing pulmonary artery, Interrupted aortic arch or Hypoplastic left heart sydrome were found. Three patients had an unusual malformation, pulmonary artery sling; other reports in literature confirmed that pulmonary artery sling with or without tracheal stenosis, is not rare in MWS. Most features were understimated in the literature, compared with out analysis. We also found ZEB2 gene full deletion to be favorable for multiple congenital heart defects and also associated with a severe cardiovascoular fenotype.
Conclusion:
This study delineated the spectrum of congenital heart defects in MWS and provided new insights into the role of different genotype determinating cardiovascoular fenotype.
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