Abstract
Congenital heart malformations are the most common type of defects found at birth. About 1% of infants are born with one or more heart defect on a yearly basis. Congenital Heart Disease (CHD) causes more deaths in the first year of life than any other congenital abnormality, and each year, nearly twice as many children die in the United States from CHD as from all forms of childhood cancers combined. Atrioventricular septal defects (AVSD) are congenital heart malformations affecting approximately 1 in 2000 live births. Babies born with an AVSD often require surgical intervention shortly after birth. However, even after successful surgery, these individuals typically have to deal with lifelong complications with the most common being a leaky mitral valve. In recent years the understanding of the molecular etiology and morphological mechanisms associated with the pathogenesis of AVSDs has significantly changed. Specifically, these studies have linked abnormal development of the Dorsal Mesenchymal Protrusion (DMP), a Second Heart Field-derived structure, to the development of this congenital defect. In this review we will be discuss some of the latest insights into the role of the DMP in the normal formation of the atrioventricular septal complex and in the pathogenesis of AVSDs.
Highlights
Atrioventricular septal defects (AVSD) are prevalent in the spectrum of defects associated with genetic disorders such as Heterotaxy Syndrome, where they are found in approximately two-third of all cases, Down Syndrome (DS), where they are observed in 20%–25% of patients, Smith-Lemli-Opitz syndrome (SLOS) were they occur in 20% of all patients, and patients with Ellis-van Creveld and Noonan syndrome [2,3]
It is important to note that the incidence of patent foramen ovale (PFO) is 40 to 50 percent in patients who suffer from a stroke of unknown cause, a condition typically referred to as a cryptogenic stroke where the PFO allows the passage of small blood clots that can lodge themselves in and block arteries of the brain
Studies described in this review show that failure of proper development of the SHF-derived Dorsal Mesenchymal Protrusion (DMP) leads to a primary atrial septal defect, the common septal defect seen in complete and incomplete AVSDs
Summary
Atrioventricular septal defects (AVSDs) form a class of congenital heart malformations found in 1 in 2000 live births [1] and in approximately 5% of all persons suffering from congenital heart disease (CHD). The most convincing experimental data linking dysmorphogenesis of the DMP with the pathogenesis of the pASD, the common component in all forms of AVSDs, (see Section 1.2), comes from studies with mouse models in which the development of the DMP has been perturbed using tissue-specific cre-recombinase mice in combination with mice carrying floxed alleles of genes playing a role in DMP development In this contribution we will review the latest insights into the molecular and cellular mechanisms associated with the development of the DMP, revisit the role of the DMP in the formation of the AV mesenchymal complex, and discuss several conditions and models in which AVSDs are observed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
