R22: Fetus with a likely chromosomal abnormality
If an ultrasound investigation reveals a fetal anomaly, it may be because of a chromosomal error. In these situations, a fetal chromosomal microarray should be considered.
Overview
Prenatal ultrasound imaging may identify features within a fetus that are suggestive of an underlying genetic aetiology. In such cases, the pregnant woman will usually be offered chorionic villus sampling or amniocentesis in order to obtain placental or fetal DNA on which to perform genomic testing.
What testing will be done?
Where a fetus has a likely chromosomal anomaly, the National Genomic Test Directory clinical indication is R22 Fetus with a likely chromosomal abnormality. This would initially activate rapid aneuploidy testing, usually via QF-PCR. Where no genetic cause is identified by this process, it is usually followed up with a chromosomal microarray. Requesting R22 will process both tests.
In addition to R22, you will need to consider R21 Fetal anomalies with a likely genetic cause. Where a single gene cause for the fetal anomaly is felt to be likely, and the phenotype fulfils the appropriate criteria, R21 can be requested via national pathways. It can be carried out after R22 or alongside R22, depending on the presenting features and the level of urgency.
Advantages and limitations of chromosomal microarray
Advantages
- Chromosomal microarray can identify deletions and duplications of chromosomal material.
- The turnaround time for a chromosomal microarray is usually two to three weeks.
Limitations
- Chromosomal microarray will not identify all genetic causes. It will miss very small duplications and deletions, as well as sequence changes within the genes.
- Arrays will not detect balanced chromosome rearrangements, and they have limited sensitivity for the detection of mosaicism.
- Microarray testing may identify variants of uncertain significance or incidental findings irrelevant to the testing indication.
Key messages
- Where a fetus has a likely chromosomal anomaly, the National Genomic Test Directory clinical indication to consider is R22 Fetus with a likely chromosomal abnormality.
- Requesting R22 will process both rapid aneuploidy testing and chromosomal microarray.
- There are both advantages and limitations to R22 – for example, it will not detect very small deletions and may not detect mosaicism.
- R21 should be considered in addition to R22, provided that the phenotype fulfils the appropriate criteria.