22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder caused by the deletion of a small segment of chromosome 22, leading to a wide range of health issues affecting multiple organ systems. Clinical features include congenital anomalies, such as heart and palate defects, as well as later-onset conditions like autoimmune diseases, endocrine and immune disorders, and speech and language delays. The syndrome is the most common chromosomal microdeletion, with a prevalence of about 1 in 1,000 fetuses. Most cases are de novo, meaning the deletion occurs spontaneously and is not inherited from parents. However, affected individuals have a 50% chance of passing the deletion to their children. The condition was first identified in patients with DiGeorge syndrome, characterized by immunodeficiency, hypoparathyroidism, and congenital heart disease. It is now known as 22q11.2DS due to the common genetic factor. The deletion is caused by abnormal chromosomal exchange near low copy repeats (LCRs), with most deletions involving a 3-Mb region. The clinical variability is not fully understood but may be due to dosage-sensitive genes, modifier genes, and epigenetic factors. The deletion leads to haploinsufficiency of about 50 genes and 7 microRNAs. Diagnosis is often delayed due to the diverse and subtle clinical presentation, and fluorescence in situ hybridization or microarray analysis is used to detect the deletion. Management requires a multidisciplinary approach tailored to each patient's specific symptoms, as the condition can present with varying severity from life-threatening to mild symptoms.22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder caused by the deletion of a small segment of chromosome 22, leading to a wide range of health issues affecting multiple organ systems. Clinical features include congenital anomalies, such as heart and palate defects, as well as later-onset conditions like autoimmune diseases, endocrine and immune disorders, and speech and language delays. The syndrome is the most common chromosomal microdeletion, with a prevalence of about 1 in 1,000 fetuses. Most cases are de novo, meaning the deletion occurs spontaneously and is not inherited from parents. However, affected individuals have a 50% chance of passing the deletion to their children. The condition was first identified in patients with DiGeorge syndrome, characterized by immunodeficiency, hypoparathyroidism, and congenital heart disease. It is now known as 22q11.2DS due to the common genetic factor. The deletion is caused by abnormal chromosomal exchange near low copy repeats (LCRs), with most deletions involving a 3-Mb region. The clinical variability is not fully understood but may be due to dosage-sensitive genes, modifier genes, and epigenetic factors. The deletion leads to haploinsufficiency of about 50 genes and 7 microRNAs. Diagnosis is often delayed due to the diverse and subtle clinical presentation, and fluorescence in situ hybridization or microarray analysis is used to detect the deletion. Management requires a multidisciplinary approach tailored to each patient's specific symptoms, as the condition can present with varying severity from life-threatening to mild symptoms.