Where the numbers collapse: sex chromosomes and microdeletions
For some conditions on the panel, a positive result is more likely to be wrong than right.
The blood test's reputation is built on Down syndrome. The rest of the panel does not perform anything like as well, and the further down the list you go, the worse it gets.
Sex chromosomes. In a planned analysis of the same large confirmed cohort:
| Result | Number analysed | Detection | Chance a positive result is correct |
|---|---|---|---|
| Monosomy X (Turner syndrome) | 17,297 | 83.3% | 22.7% |
| Sex chromosome trisomies combined | 10,333 | 70.4% | 82.6% |
A positive result for Turner syndrome from this test is wrong roughly three times out of four. It also misses about one in six cases that are there. The authors say so directly: The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower.
Microdeletions. A microdeletion is a small missing piece of a chromosome. The most-marketed one is called 22q11.2 deletion syndrome. In a study of 20,887 pregnancies with genetic outcomes for 18,289 of them, there were 12 confirmed cases, a rate of about 1 in 1,524.
With the original method, more than three quarters of positive results were false. With an updated algorithm the test did better, but the range still runs from 28.9% to 75.6%, which is to say that even now it might be right most of the time or wrong most of the time.
Zero is not a rounding artefact. Every single flagged case of those two that came for confirmation was a false alarm. The laboratory's own explanation: it happens
likely because of the low prevalence of the individual targeted microdeletion syndromes in the general population.
We do not recommend routine general population screening for any microdeletion condition.It adds that anyone who does choose 22q11.2 screening should do so only after proper counselling first, and that a woman who wants information about missing or extra pieces of chromosome should be offered a diagnostic test instead of this screen.
If a microdeletion panel was added to your blood test without a conversation, that is a departure from current guidance, and it is reasonable to say so.
"If this comes back positive for a microdeletion, how likely is it to be a false alarm?"
"I would like to opt out of any part of this test that ACOG does not recommend routinely."