“ THE SUDDEN SOUL REAPER ”-HYPERTROPHIC CARDIOMYOPATHY – ITS EMBRYOLOGICAL BASIS

Hypertrophic Cardiomyopathy is an inherited disorder that affects the muscle of the heart or the Myocardium. This condition results from a mutation to several genes that affects the production of cardiomyocytes proteins and therefore lead to an abnormal thickening and enlargement of the heart walls. That myocardial thickening induces rigidity and stiffness that reduces the heart efficiency of contractility and narrows the capacity of its cavities. Nonetheless it can cause an irreversible damage to the myocardial tissue producing a scar tissue that interferes with the heart electric activity and rhythm which may end with a life-threatening arrhythmia and death. © 2016 Elixir All rights reserved. Elixir Embryology 99 (2016) 43284-43288 Embryology Available online at www.elixirpublishers. com (Elixir International Journal) Ganesh Elumalai and Emad Abdulrahim Ezzeddin / Elixir Embryology 99 (2016) 43284-43288 43285 Figure 1. Shows that the HCM has a greater incidence than other more recognized congenital diseases names. When looking at the testing results that became available in 2015, cardiac MRI (Magnetic Resonance Imaging) and genetic testing for HCM; they cleared to our view that HCM may be even more common than what has been thought. As the results showed that the number of those with HCM increased to 1 in 200-300 [5]. Therefore, estimated numbers for the presence of HCM is somewhat close to more than 1 million of US population, and 36 million or more worldwide [5]. Normal Embryological Development of the Cardiac Muscle The heart is consisted primarily of three layers. The first layer is the innermost layer and it is called the Endocardium. This layer is thin and it covers the surface of the inner champers of the heart (atria and ventricles). The second layer is the layer that consists of the heart muscle. It is called the Myocardium and this layer is a thick muscular layer that obtains the ability to contract forcefully and elastically in order to pump the blood all over the body. The third layer is the Epicardium and it is the visceral layer of the pericardial sac which contains a small amount of a lubricating fluid in it that plays a role of protecting and facilitating the heart movement inside the chest cavity while contracting [6]. As the Myocardium (the heart muscle layer) is a part of the heart, and the heart in consequence is a part of the Cardiovascular System, this system originates from the Progenitor Heart Cells that lies in the Epiblast of the Bilaminar Disk embryo in the second week of gestation. Those Progenitor Heart Cells appear immediately adjacent to the cranial end of the primitive streak and then they migrate on the 16 th day of gestation from there to the splanchnic layer of the Lateral Mesoderm Plate (Fig-2), as they arrive in the middle of the third week. Those cells arrange in a horseshoeshaped cluster (or blood islands) of cells called the Primary Heart Field cranial to the neural folds [7]. Figure 2. Heart islands position in second week embryo. A great number of blood islands and cardiac myoblasts develop from the PHF (Primary Heart Field) and they are the precursors that will form the blood cells and the vessels of the cardiovascular system. Their development is induced by the underlying pharyngeal endoderm. This region where the blood islands and Myoblast clusters occupy is hence called the cardiogenic region. In addition to the cardiogenic region a pericardial cavity develops over it from an adjacent part of the intra-embryonic cavity. As time progresses the blood islands start uniting to form a similar horseshoe-shaped endothelial lined tube that is surrounded by the myoblast cells, forming the heart tube [7]. As the embryo starts to fold cephalo-caudally and laterally simultaneously the cardiogenic region that was primarily anterior to the cranial end of the neural fold it starts to reposition towards the cervical then the thoracic region where it settles eventually (Fig-3&4). Upon the closer of the embryonic folds the caudal regions of the paired heart tubes merge while the central part of it expands to make the future outflow and ventricular heart regions. On the 22 nd day of gestation the developing heart tube is consisted of an endothelial layer that makes the lining of the tube and a myocardial layer that originates the heart muscular tissue that in the future progresses to structure the Myocardium [7]. The cardiomyocytes (cardiac muscle cells) of the myocardium under a normal genetic development arrange in a regular organization of branched bundles of cells lying in smooth straight lines (Fig-5). Those cardiomyocytes contain serial sets of sarcomeres, which are subunits of striated myofibrils. Those myofibrils are an alteration and interlacing of light microfilaments that are composed of Actin protein and heavy dark microfilaments that are composed of Myosin protein [8]. Congenital Anomalies Correlations of Hypertrophic Cardiomyopathy Condition The congenital anomalies are the most common causes for the death in infants under one year of age [9, 10, 11, 12, 13]. HCM (Hypertrophic Cardiomyopathy) is in a main aspect a genetic disease. It results from a mutation in one or several genes (1 to 9 genes at least) that are responsible of the synthesis of sarcomere proteins in the cardiomyocytes (heart muscle cells) [14]. A prominent gene mutation (in 45% of cases) is due to a deletion-alteration of the 14qll.2-3 genes that are responsible of the manufacturing of the β-Myosin heavychain, a protein that composes the heavy microfilaments of the sarcomeres inside cardiomyocytes [14]. Figure 3. Cardiogenic Region Repositioning in Third