F11-

V2-

2018

629

Cenata GmbHPaul-Ehrlich-Str. 2372076 Tübingen

Tel: +49 7071 565 44 430Fax: +49 7071 565 44 444

www.cenata.deinfo@cenata.de

Microdeletion 22q11.2(DiGeorge syndrome)

References[1] McDonald-McGinn et al. GeneReviews 1999 Sep 23

[2] Grati FR et al. Prenat Diagn. 2015; 35: 801–809

[3] McDonald-McGinn et al. Genet Med. 2001; 3: 23–29

[4] McDonald-McGinn et al. Genet Couns. 1999;10(1):11-24

[5] McDonald-McGinn, et al. Nat Rev Dis Primers. 2015 Nov 19;1:15071

[6] Schmid M et al. Fetal Diagn Ther. 2017 Nov 8, E-pub ahead of print

[7] Stumm M, Schröer A. Gynäkologe 2018; 51: 24-31

Results on average in 3 working days

© 2018 Cenata GmbH. All rights reserved. Cenata® and the Cenata logo are registered trademarks of Cenata GmbH. Harmony® is a trademark of Roche. All other trademarks are the property of their respective owners.

DiGeorge syndrome (Microdeletion 22q11.2)

PREVALENCE AND GENETICS

DiGeorge syndrome is the second most common cause of a

delay in fetal development and of severe congenital heart defects.

The postnatal prevalence is about 1: 4000 to 1: 6000 [1]. Recent

data show that the prenatal prevalence can reach up to 1: 1000 [2].

The DiGeorge syndrome is caused by a submicroscopic deletion

in chromosome 22. In most cases the size of the deletion is about

3 million bases (Mb), but in about 10-15% of cases it can be even

smaller (1.5 MB or less.)

In 90 % of the cases DiGeorge syndrome develops "de novo", by

a spontaneous genetic mutation not inherited from the parents [3].

In contrast to trisomy 21, 18 and 13, maternal age is not a risk factor

for the occurance of microdeletions.

CLINICAL ASPECTS

The clinical severity of the DiGeorge syndrome varies depending on

the size and position of the deletion [2]. About 75% of all newborns

with DiGeorge syndrome suffer from heart defects. Additionally the

following disorders are typically associated with it [4, 5]:

▪ Immunodeficiency and hypocalcemia due to hypoplasia of

the thymus and parathyroid glands

▪ Facial anomalies

SCREENING WITH THE HARMONY® TEST

A prenatal screening with the Harmony® Test for DiGeorge

syndrome is possible from gestational week 10 + 0 onward.

The proprietary DANSR-Assay (digital analysis of selected

regions) of the Harmony® Test is able to detect 75% of all

22q11.2 microdeletions, including those smaller than 3 Mb at a

false-positiverate of 0.5% [6].

The screening for DiGeorge syndrome by the Harmony® Test

determines the probability for the presence of the genetic

disorder, however, it is not able to ascertain the clinical severity of

the microdeletion.

In singleton pregnancies the analysis for DiGeorge syndrome can be

added to all other test options.

As each additional test increases the overall false-positive

rate of a non-invasive prenatal test [7], we recommend

requesting the test option only in pregnancies with an increased

risk for this microdeletion.

As in screening for trisomies, screening for DiGeorge syndrome

can lead to false-positive results. Therefore, a report indicating

a high risk for the microdeletion has to be confirmed by an

invasive diagnostic procedure (array-CGH), before further

actions can be taken. For any questions please contact the medical

or scientific support team of Cenata.

Schematic depiction of microdeletion 22q11.2

Frequency of different microdeletion 22q11.2 variants

Singletonpregnancy

Twinpregnancy > 2 fetuses

Trisomy 21, 18, 13 x

Trisomy 21, 18, 13 and X/Y analysis x x

DiGeorge syndrome(Microdeletion 22q11.2) x x

Fetal sex determination x

Harmony® Test options