CVS mosaic i(21) → normal amnio FISH but 1 abnormal amnio cell — CPM vs. mosaic Down syndrome? Looking for similar experiences
I’m looking for anyone who has had a similar experience with isochromosome 21 / mosaic trisomy 21 on CVS followed by mostly normal amniocentesis results, particularly anyone who was ultimately diagnosed with confined placental mosaicism (CPM).
This has been an incredibly stressful and confusing pregnancy, and we’re currently waiting on the final microarray while trying to understand what the results so far actually mean.
Here is our timeline:
12w5d ultrasound
NT was 3.56 mm
Nasal bone present
No other abnormalities noted
NIPT
Low risk for trisomy 21
Because of the slightly increased NT, we proceeded with CVS.
CVS FISH
Normal female result
Normal copy number for chromosomes X, 13, 18 and 21
Initially tested 100 nuclei, and I was later told the CVS FISH was re run on approximately 500 cells
No trisomy 21 detected
Then came the unexpected result:
CVS karyotype
46,XX,i(21)(q10)[15]/46,XX[5]
So 15/20 cells showed an isochromosome 21 and 5/20 were normal.
The report interpreted this as mosaicism for an isochromosome 21, resulting in trisomy of the long arm of chromosome 21.
We subsequently had CVS genome sequencing, which also detected i(21) mosaicism at approximately 20–21%.
At that point we were obviously very concerned about mosaic Down syndrome, but we were told that because CVS samples the placenta, this could potentially represent confined placental mosaicism (CPM) and that amniocentesis would be needed to better assess the fetus.
Amniocentesis
The amnio FISH came back NORMAL.
The report showed a normal female result with normal copy numbers for X, 13, 18 and 21 in all tested nuclei.
We were hopeful, but then the full karyotype came back:
46,XX,i(21)(q10)[1]/46,XX[104]
So:
104/105 metaphases were normal female cells
1/105 metaphases contained i(21)
The lab notes that two trisomy-21 cells were actually identified within the same colony from one culture
The other cultures/colonies were normal
No other consistent chromosome abnormalities were found
The lab specifically commented that because i(21) had previously been identified on the CVS, the amniotic-fluid finding should be carefully correlated with the CVS.
So this is where we are now.
The discrepancy is huge:
CVS:
15/20 abnormal by karyotype
~20–21% mosaicism by genome sequencing
Amnio:
Normal FISH
104/105 normal metaphases
Only one abnormal metaphase, with the two abnormal cells confined to one colony from one culture
Our fetal imaging has also been reassuring:
Nuchal fold at ~16 weeks: 3 mm
No other soft markers on the anatomy scan
Growth measurements have been generally appropriate
Fetal echocardiogram was normal
We are currently waiting for the GeneDx microarray on the amniotic-fluid specimen.
What I’m trying to understand
Has anyone experienced something similar where:
CVS showed significant mosaic i(21)/T21 → amnio FISH was normal → amnio karyotype found only one/few abnormal cells, particularly confined to one colony → ultimately diagnosed with CPM or had a healthy baby.
My MFM and genetic counselors have been great, but have limited experience in this situation. I’m pursuing a second opinion at Columbia at the moment. Mo