Genetics of ebstein anomaly

Ebstein anomaly (EA) is a rare etiologically heterogeneous congenital malformation of the tricuspid valve, accounting for less than 1 % of all congenital heart defects (CHDs) and for 0.3-0.8 % of all patients presenting with CHD in the first year of life. The prevalence of EA is estimated as 1 in 20,000-50,000 live births, with equal male to female occurrence. In the majority of the cases, EA is an isolated non-syndromic defect (80 %), while it is associated with extracardiac anomalies in the setting of chromosomal or Mendelian disorders in about 20 % of the patients. The role of teratogens in the etiology of EA has also been suggested, following the report of lithium therapy during the first trimester of pregnancy and the occurrence of EA in the fetus, although more recent case-control epidemiological studies have not confirmed these findings. Clinical epidemiological data before the advent of the new cytogenetic and molecular techniques have shown that EA is non-syndromic in about 77 % of the cases, while chromosomal syndromes were detectable in 5 %, monogenic syndromes in 12 %, and undiagnosed associations with major organ malformations or deformations in the remaining 6 %. More recent observations have added the contribution of microchromosomal anomalies detectable by array CGH as the cause of syndromic EA.