What is the embryology of endocardial cushion defects?

Embryology of Endocardial Cushion Defect

Endocardial cushion defects arise from abnormal development of the endocardial cushions, which are essential structures that contribute to the formation of the atrioventricular (AV) valves and septa during cardiac development.

Normal Cardiac Development

• The heart begins as a primitive heart tube formed from early cardiac progenitor cells in the anterior mesoderm (primary heart field) 1
• The heart tube undergoes rightward looping, leading to formation of primitive ventricles and atria 1
• The endocardial cushions develop in the atrioventricular canal region between the primitive atrium and ventricle

Endocardial Cushion Formation

1. Initial Structure: The early heart tube consists of:

   • An outer myocardial cell layer
   • An inner endocardial cell layer
   • Extracellular matrix (cardiac jelly) between these layers 2

2. Endocardial-to-Mesenchymal Transformation (EMT):

   • Endocardial cells delaminate from the surface of the cushion
   • These cells undergo transdifferentiation into mesenchymal cells
   • In mice, this process begins in the atrioventricular canal at embryonic day 9 (E9) 2
   • The mesenchymal cells then invade the cardiac jelly, proliferate, and populate the endocardial cushion

3. Cushion Growth and Fusion:

   • Superior (dorsal) and inferior (ventral) endocardial cushions form in the atrioventricular canal
   • These cushions grow toward each other and eventually fuse
   • The fused cushions contribute to the formation of:
     • Atrioventricular septum
     • Portions of interatrial and interventricular septa
     • Parts of the mitral and tricuspid valves 3

Pathogenesis of Endocardial Cushion Defects

Endocardial cushion defects (also called atrioventricular septal defects or AV canal defects) result from failure of proper endocardial cushion development and fusion. The key abnormalities include:

1. Cellular Abnormalities:

   • Reduced number of cardiac mesenchymal cells
   • Lower cellular density in the cushions 4
   • Abnormal cushion shape (elongated) 4

2. Molecular Abnormalities:

   • Delayed expression of extracellular matrix components like cytotactin and fibronectin
   • Abnormal expression of heparan sulfate on cardiac mesenchymal cells 4

3. Architectural Abnormalities:

   • Subtle abnormalities in heart tube architecture
   • Altered angle between the atrioventricular canal and pharyngeal structures 5

Types of Endocardial Cushion Defects

According to the European Heart Journal guidelines, endocardial cushion defects can be classified as 6:

1. Partial AVSD (Partial AV Canal):

   • Defect only at the atrial level (primum ASD)
   • Separate left and right AV valve orifices
   • Anterior and posterior bridging leaflets are fused centrally

2. Complete AVSD (Complete AV Canal):

   • Septal defect extends into both interatrial and interventricular septum
   • Single common AV valve orifice
   • No central fusion of bridging leaflets

Clinical Associations

• Down Syndrome: Strong association with endocardial cushion defects

  • 35% of patients with AVSD have Down syndrome
  • Most complete AVSDs occur in Down syndrome patients
  • Most partial AVSDs occur in non-Down syndrome patients 6

• Other Associations:

  • Tetralogy of Fallot
  • Other conotruncal anomalies
  • Heterotaxy syndromes 6

Anatomical Features

• Common AV valve annulus stretching across both ventricles
• Five leaflets guarding the common AV valve
• Abnormal position of the AV node (posterior and inferior to the coronary sinus)
• Displaced bundle of His and left bundle branch (posteriorly)
• Abnormal ventricular activation sequence 6

Understanding the embryology of endocardial cushion defects is crucial for comprehending the anatomical abnormalities seen in these patients and for planning appropriate surgical interventions.