22q11.2 deletion syndrome
Older names: DiGeorge syndrome, CATCH 22, Velocardiofacial syndrome VCFS.
22q11.2 deletion syndrome has very large variability, even between people in a family having the same deletion. Many different organs may be affected. The most commonly occurring is heart malformation, cleft palate and underdevelopment of the thymus and thyroid glands. Common symptoms include feeding difficulties, speech and language disorders, infection susceptibility due to immune deficiency, learning difficulties and neuropsychiatric problems. Teeth, hearing, vision and growth can be also be affected. Underdevelopment of the thyroid glands may cause calcium deficiency which may cause seizures. The severity of the various symptoms can vary from very mild to severe.
Early diagnosis allows several of the problems to be treated at birth and in the newborn period, thus giving milder symptoms.
Genetics of 22q11.2 deletion syndrome
22q11.2 deletion syndrome is estimated to occur in approximately 1 in 4,000 born children. In about 90% of cases, there is a new chromosome change that is not found in any parent. In about 10% of cases, the syndrome is dominantly herited from one of the parents. The likelihood of giving birth to a child with 22q11.2 is independent of the mother’s age.
85% of cases have 3 megabases of DNA lacking (deletion) on the long arm of chromosome 22, others have lost a smaller part in the same area.
Harmony NIPT is designed to detect both the larger and the smaller deletions, unlike many other NIPT technologies that only detect the largest deletions.
Why not a wider panel that includes more microdeletions?
The advantage of Harmony NIPT is to avoid unnecessary amniocentesis / CVS.
Although the NIPT technologies are very good, a small number of results always appear, which falsely indicates a high probability of abnormality. These false alarms become more frequent the more abnormalities that are analyzed for, and if the abnormality in question also appears extremely rare, which applies to almost all microdeletions (1/10 000 – 1/100 000 births), the result is that the analysis makes more harm than good by causing an increase in the number of unnecessary amniocentesis / CVS.
For example, about 300-400 amniocentesis may be required to identify a true case of a microdeletion that occurs in 1 in 50,000 births.
We think this is not reasonable and therefore does not offer a wide panel of extremely rare syndromes with Harmony NIPT.