microdeletion 22q11.2 (digeorge syndrome) · digeorge syndrome is the second most common cause of a...
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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
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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