Can Blood Testing Miss Mosaic Trisomy 18? Other Tissue Tests

Yes, a postnatal diagnostic blood test—like a karyotype or a chromosomal microarray—can sometimes miss mosaic trisomy 18. If a person has physical signs or medical issues (often called clinical findings) that suggest a genetic condition, but their blood test comes back normal, it is possible that the extra chromosome 18 is present in other tissues of their body but not in their blood ^[1][2]. However, a normal result might also mean they truly do not have trisomy 18, and a different diagnosis is the cause.

Understanding Different Genetic Tests

Genetic tests have different strengths and limitations when looking for a mosaic condition (where some cells have an extra chromosome and some do not).

• Karyotype: A traditional test that takes a picture of the chromosomes to count them. It requires cells to be grown (cultured) in a lab. It can miss mosaicism if the laboratory only examines a small number of cells, or if the typical cells grow faster in the lab and “outcompete” the trisomy 18 cells during culture ^[3][4].
• Chromosomal Microarray (CMA): This test checks the DNA for missing or extra pieces. It usually does not require cells to be grown in a lab, which avoids culture bias. However, a microarray has a limit on how small of a mosaic fraction it can detect and can miss low levels of mosaicism ^[5][3].
• FISH (Fluorescence In Situ Hybridization): This test uses fluorescent probes to light up and count specific chromosomes (like chromosome 18) in individual cells. It is often used on uncultured cells to look for low-level mosaicism ^[6].

None of these tests is perfectly sensitive in every situation, and every laboratory has a different detection limit.

Why Might Blood Be Normal?

When an embryo first begins to grow, all of its cells multiply. If a change (like an extra chromosome) happens in some cells but not others, the resulting cell lines (populations of cells) can be distributed unevenly throughout the body as the fetus develops ^[2][7].

Because of this uneven distribution, a person might have a significant number of cells with the extra chromosome in their internal organs or skin, but very few or none in their bloodstream ^[8]. Importantly, the level of mosaicism found in the blood does not tell doctors how much is in the rest of the body, and it cannot reliably predict the severity of the person’s medical condition or which organs are affected ^[9][7].

Testing Other Tissues

Because a normal blood test does not guarantee the rest of the body is normal, a clinical genetics team may recommend testing a different tissue if they still strongly suspect mosaic trisomy 18. This is not done automatically, but rather to answer a specific medical question ^[2].

• Buccal (Cheek) Swab: A simple swab of the inside of the cheek collects a different population of cells than a blood draw. Testing these cheek cells (often using FISH) can sometimes reveal a mosaic cell line that the blood test missed ^[7][6].
• Skin Fibroblasts: A doctor may perform a minor skin biopsy to test fibroblasts (connective tissue cells). The biopsy involves a small procedure, often with local numbing, that leaves a tiny scar. Testing these cells may detect or help confirm mosaic trisomy 18 in patients who have undetectable levels in blood or cheek swabs ^[10][8].
• Other Surgical Tissues: If a patient is already having a clinically necessary surgery, the genetics team and surgeons can coordinate in advance to send a small piece of the removed tissue for genetic testing. Surgery should never be performed or delayed solely to get a genetic sample.

Limitations of Additional Testing

Every tissue specimen has limitations. A cheek swab or skin biopsy might still fail to detect mosaicism if the abnormal cells are present at extremely low levels or simply happen to be absent from that specific spot ^[11]. Furthermore, skin biopsies require the cells to be cultured in a lab, which carries the risk of culture bias where normal cells grow faster than the trisomy 18 cells ^[3].

A normal result from a cheek swab or skin biopsy simply means the extra chromosome was not found in that specific sample—it does not definitively prove that the extra chromosome is absent from every organ ^[11][8].

Ultimately, testing another tissue is a specialized decision. Families should work with a medical genetics team to decide if more testing is helpful, while continuing any necessary medical care or symptom management in the meantime. Waiting for a genetic diagnosis should not delay treatment for heart, feeding, or developmental needs.