The history of the syndrome, previously referred to as DiGeorge, includes the following discoveries:

• In the mid 1960s, an endocrinologist named Angelo DiGeorge, MD, recognized that a particular group of clinical features frequently occurred together, including the following:
  
  
  • hypoparathyroidism (underactive parathyroid gland), which results in hypocalcemia (low blood calcium levels)
    
    
  • hypoplastic (underdeveloped) thymus or absent thymus, which results in problems in the immune system
    
    
  • conotruncal heart defects (i.e., tetralogy of Fallot, interrupted aortic arch, ventricular septal defects, vascular rings)
    
    
  • cleft lip and/or palate
    
    

  The name of DiGeorge syndrome was applied to this group of features.

• In the 1970s, Robert Shprintzen, PhD, a speech pathologist, described a group of patients with similar clinical features including cleft lip and/or palate, conotruncal heart defects, absent or hypoplastic thymus, and some of these patients also had hypocalcemia. Dr. Shprintzen named this group of features velo-cardio-facial syndrome, but the syndrome was also referred to as Shprintzen syndrome.
  
  
• In the 1980s, the technology was developed to identify an underlying chromosome defect in these syndromes. It was determined that over 90 percent of all patients with features of DiGeorge, Shprintzen, and velo-cardio-facial syndromes had a chromosome deletion in the region of 22q11. In other words, this was the same syndrome, but because several different researchers in different areas of expertise had described it, the syndrome carried multiple names. Many physicians and researchers today use the term 22q11 deletion syndrome because it describes the underlying chromosome problem, or velo-cardio-facial syndrome (VCFS) because it describes the main body systems involved. However, for the purposes of this content, we will call it DiGeorge syndrome.

As mentioned, 90 percent of patients with the features of this syndrome are missing a small part of their chromosome 22 at the q11 region. This region encompasses about 30 individual genes and results in developmental defects in specific structures throughout the body. It is not known why this region of chromosome 22 is prone to become deleted, but this is one of the most frequent chromosome defects in newborns. Deletion 22q11 is estimated to occur in one in 3,000 to 4,000 live births. Most of the 22q11 deletion cases are new occurrences or sporadic (occurs by chance). However, in about 10 percent of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. The gene is autosomal dominant, therefore, any person who has this deletion has a 50 percent chance of passing the deletion to a child. For this reason, whenever a deletion is diagnosed, both parents are offered the opportunity to have their blood studied to look for this deletion.

Approximately 10 percent of individuals who have the features velo-cardio-facial syndrome (VCFS) do not have a deletion in the chromosome 22q11 region. Other chromosome defects have been associated with these features, as have maternal diabetes, fetal alcohol syndrome, and prenatal exposure to Accutane.