My patient’s NIPT is positive for a deletion of 22q11.2. What does this mean?

Your patient’s screening test detected a deletion of 22q11.2 which is associated with 22q11.2 deletion syndrome (also known as DiGeorge syndrome or Velocardiofacial syndrome). NIPT is a screening test; false positives, though rare, can occur.

Next steps to consider: You should discuss the results and the potential clinical implications with your patient. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine state, “All women with a positive cell-free DNA test result should have further detailed counseling and testing and should have a diagnostic procedure before any irreversible action is taken.” Confirmation prior to birth can also help with pregnancy and neonatal management.

What is 22q11.2 deletion syndrome?

22q11.2 deletion syndrome is a genetic disorder that is caused by the deletion of a small piece of chromosome 22, containing approximately 30-40 genes.

What are the features of 22q11.2 deletion syndrome?

Key features of this syndrome are variable, can affect almost any part of the body, and commonly include: intellectual disability, heart defects, palatal abnormalities, immune deficiency, and dysmorphic features. Life span is usually normal but can vary depending on severity of features.

What is the prevalence of this condition?

Approximately 1 in 4,000 live births have this condition. 22q11.2 deletion usually happens by chance and is not typically associated with advanced parental age.

What testing should be considered?

  • NIPT can only screen for cases of 22q11.2 deletion syndrome caused by the common 3 million base pair deletion, which accounts for 85% of patients with DiGeorge/velocardiofacial syndrome.
  • Specialized genetic tests such as fluorescence in situ hybridization (FISH) and microarray are available to confirm the presence of 22q11.2 deletion syndrome.
  • These confirmatory tests are generally performed on cells from chorionic villus sampling (CVS) or amniocentesis during pregnancy, on cord blood or peripheral blood sample after the baby is born, or on products of conception (POC) in case of a miscarriage.
  • Ultrasound evaluation may be useful in aiding with a prenatal diagnosis of 22q11.2 deletion syndrome, but a normal ultrasound cannot exclude this condition.
Resources for 22q11.2 deletion syndrome
The International 22q11.2 Foundation Inc.
Genetics Home Reference/Medline Plus
References for 22q11.2 Deletion Syndrome :
  1. Das Chakraborty R, Bernal AJ, Schoch K, et al. Dysregulation of DGCR6 and DGCR6L: psychopathological outcomes in chromosome 22q11.2 deletion syndrome. Transl Psychiatry. 2012;2:e105.
  2. Nussbaum RL, McInnes RR, Willard HF. Thompson & Thompson Genetics in Medicine. 7th ed. Philadelphia, PA: Saunders Elsevier; 2007.