Imagine you are an expectant parent. Just a couple of months into your pregnancy, you opt for an easy genetic screen. A result comes back: the fetus is likely missing a chunk of DNA at site 11.2 on the long arm of the 22nd chromosome—a variant associated with serious medical and developmental issues.
You go online and learn that at least 1 in 4,000 people have this “22q11.2” microdeletion, but the true figure may be much higher. You read about 22q11.2 deletion syndrome’s 180-plus symptoms, including heart malformations, hypocalcemia, intellectual disability, autism and schizophrenia. You discover the bewildering treatment guidelines, the specialist clinics scattered throughout the country, and the vibrant patient advocacy movement spearheaded by the International 22q11.2 Foundation.
Yet the same pathogenic variant—a genetic change or “mutation” known to cause disease—has been found in people with much milder symptoms, and some who barely seem affected at all. No one can give you solid risk factors because our knowledge of 22q11.2 deletion syndrome (also known as DiGeorge syndrome) is riddled with “ascertainment bias”: only people with telltale problems are... see more