© 2016            

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

BackgroundFetal DNA from the trophoblasts circulating in the maternal circulation make it possible for laboratories to screen for Fetal DNA during pregnancy.  Fetal DNA represents approximately 10-14% of Cell Free DNA in the maternal circulation.

Maternal Fetal Circulating Cell Free DNA (cf DNA) or microarray studies have helped uncover microdeletions – losses of very small pieces of chromosome(s) that are not visible under a microscope and can be associated with syndromes in a child.

Recently, we saw a 36 year old female with one healthy child at approximately 10 weeks gestation who tested “High Risk”

(1 in 20) for a having a child with 22q11.2 Deletion Syndrome.

Prior to Maternal Fetal DNA screening tests or microarray in pregnancy, the only way that a patient would know if they had child with a microdeletion was at delivery with an “affected” child.

DiGeorge Syndrome (22q11.2 Deletion Syndrome): Is characterized by heart problems, kidney problems, and/or immune system problems, movement problems and seizures. This syndrome is caused by a loss or rearrangement of a small portion of the long arm of chromosome #22 [22q11.2].

  • Approximate Incidence – 1 in 2,000 births.

The 22q11.2 Deletion Syndrome has several names attributed to it because of the variability of the presentation. The syndrome has also been called Velocardiofacial Syndrome describing involvement of the palate, heart and face, Shprintzen Syndrome or DiGeorge Syndrome.


Findings can include:

  • cleft palate
  • hearing, speech and learning problems
  • facial changes including small chin
  • low set ears and wide set eyes
  • delayed growth and feeding difficulties
  • poor muscle tone,
  • heart defects such as interrupted aortic arch, common outlet for aorta and pulmonary arteries, ventricular septal defect or Tetralogy of Fallot
  • frequent infections due to hypoplasia of the thymus
  • low calcium due to hypoparathyroidism
  • decreased kidney function.

Approximately 10% of 22q11.2 deletion syndrome cases are familial being inherited from a parent who might have mild symptoms or be unaware of the 22q11.2 deletion in one of their #22 chromosomes.

Approximately 90% of cases are due to a new deletion in that individual and will place each of their children at a 50% (1:2) risk of inheriting the deleted chromosome #22.

At the current time the value of “routine” screening for Microdeletions on all patients is controversial because of the low prevalence of these disorders and the possibility of “false positive” and “false negative” results.

However, when a patient is identified as a candidate for invasive testing i.e. Chorionic Villus Sampling (CVS) and/or amniocentesis, the addition of Microdeletions may be indicated, particularly if family history or ultrasound findings suggest an increased possibility for detection of one of these rare disorders.