Charge syndrome is caused due to mutation of CHD7 gene and is transmitted from parents to the child through an autosomal dominant pattern. Though mutation on the CHD7 gene is considered to be one of the primary Charge syndrome causes, studies have form that abnormalities or mutation on other genes including SEMA3E, which is completely unrelated to the CHD7 gene, have also manifested symptoms similar to the Charge Syndrome. Estimates have suggested that about 90 % of the charge syndrome causes are attributed to mutation or defect in CHD7. The remaining anomalies are attributed to pathologic and cytogenetic abnormalities including 14a22-q24.3 duplication, 9p- and single gene mutations and 22q11.2 deletion.
Charge Syndrome CausesPatho-physiology can explain how mutations of the genes are important Charge Syndrome causes:
• As a result of the gene defect, the embryonic differentiation stops after the second month of gestation. Embryonic differentiation is the process by which the precursor cells differentiate into specific organ cells. This process is also result to as organogenesis. As a result some of the organs that are in the formative stage tend to get affected which include the eye, choanae, cardiac septum, cochlea and external ear. Most of these organs develop between the fourth and the sixth week of gestation.
• Also the gene defect can stop the development of the prechordal mesoderm which is essential for the development of the mid face and the subsequent development of the prosecephalon, which is the part of the brain.
• There are different mechanisms that have been found to result in the stoppage of the embryonic differentiation. These suggested mechanisms include:
• Deficiency in the migration of the cervical crest cells to the pharyngeal arches
• Deficiency in the formation of the mesoderm
• Defective interaction between the crest cells and mesoderm which in turn results in defects in blastogenesis.
Unfortunately, there is little known information about why the mutations take place and whether they are spontaneous in nature.