Causes of 22q11 DiGeorge Syndrome
22q11 DiGeorge Syndrome, also known as 22q11.2 deletion syndrome or velocardiofacial syndrome, is a genetic disorder caused by the deletion of a small piece of chromosome 22. This deletion occurs during early fetal development and affects multiple organ systems, leading to a wide range of symptoms and complications.
Genetic Mutation:
The primary cause of 22q11 DiGeorge Syndrome is a spontaneous genetic mutation that occurs during the formation of reproductive cells or early embryonic development. This mutation leads to the deletion of a specific region of chromosome 22, known as 22q11.2. The exact mechanism behind this mutation is not fully understood, but it is believed to be a result of errors in DNA replication or recombination.
Deletion of Chromosome 22q11.2:
The deletion of the 22q11.2 region is the hallmark genetic abnormality in individuals with DiGeorge Syndrome. This deletion can vary in size and may involve the loss of several genes. The specific genes affected by the deletion play a crucial role in the development of various organs and systems in the body.
Role of TBX1 Gene:
One of the most important genes within the deleted region is the TBX1 gene. This gene is responsible for regulating the development of various structures, including the heart, face, and thymus gland. The loss of TBX1 function contributes to the characteristic features of DiGeorge Syndrome, such as congenital heart defects, facial abnormalities, and immune system dysfunction.
Spontaneous De Novo Mutation:
In most cases, the deletion of chromosome 22q11.2 occurs as a spontaneous de novo mutation, meaning it is not inherited from either parent. The mutation arises randomly during the formation of reproductive cells or early embryonic development. However, individuals with DiGeorge Syndrome have a 50% chance of passing the condition on to their offspring.
Parental Chromosomal Translocation:
In rare cases, DiGeorge Syndrome can be inherited from a parent who carries a balanced chromosomal translocation involving chromosome 22. A balanced translocation occurs when a piece of one chromosome breaks off and attaches to another chromosome without any genetic material being lost. If a parent carries this translocation, they have an increased risk of passing on the 22q11.2 deletion to their children.
Environmental Factors:
While the primary cause of DiGeorge Syndrome is genetic, certain environmental factors may influence the severity and presentation of symptoms. For example, maternal exposure to certain medications, drugs, or infections during pregnancy may increase the risk of developing DiGeorge Syndrome or worsen the symptoms in affected individuals.
Conclusion:
22q11 DiGeorge Syndrome is primarily caused by a spontaneous genetic mutation resulting in the deletion of chromosome 22q11.2. The loss of specific genes, including the TBX1 gene, contributes to the characteristic features and complications associated with the syndrome. While most cases are not inherited, individuals with DiGeorge Syndrome have a 50% chance of passing the condition on to their offspring. Understanding the underlying causes of DiGeorge Syndrome is crucial for early diagnosis, management, and genetic counseling.