How can a person request testing for mosaic Down syndrome?

     The first step to arrange for testing for mosaic Down syndrome is to make an appointment with a genetics specialist. Some areas may not have genetics practice available. For those regions, you may wish to contact your family’s general health physician (pediatrician; neurologist; family practice physician). 

     The genetics team will evaluate your child (or you) to determine if the cause for symptoms is most likely to be mosaic Down syndrome or some other genetic condition. This step is important to avoid ordering/paying for testing that is unlikely to provide answers to the health and/or behavioral concerns noted in your child/yourself. The genetics team will order the testing, using accredited testing labs. They will also help address insurance questions/information needed for diagnostic testing (this test is covered by most insurance companies). The genetics team will also make sure that you have the referrals you need to ensure your child/you receive(s) the best medical care and intervention services.

How is testing completed to diagnose mosaic Down syndrome?

     Testing to diagnose mosaic Down syndrome is completed by a genetics laboratory that is accredited to perform diagnostic testing. The individual’s chromosomal make-up can be evaluated using either: (1) a conventional chromosome test; (2) a fluorescence in situ hybridization test; or (3) a microarray test.

• 1.      Conventional chromosome test:  This test is most frequently used for evaluating a person to determine if he or she has Down syndrome or mosaicism for trisomy 21.  This test is usually completed from a blood specimen but can also be completed from a skin biopsy. The analysis includes an assessment of the number of chromosomes present, as well as the structure of the chromosomes. This test can distinguish if a person has Down syndrome/mosaic Down syndrome due to an additional structurally normal chromosome 21 or if they have Down syndrome/mosaic Down syndrome as a result of a chromosome rearrangement (such as a translocation). Given that this test also involves an analysis of all chromosomes, it can identify other chromosomal findings that are present (not just Down syndrome). Typically, 20 cells are evaluated in this test.  If the request for testing is to rule out mosaicism, typically 30 to 50 cells will be evaluated. By evaluating 20 cells, labs will be able to detect mosaicism if it is present in as few as 11% of cells; By scoring 30 cells, the lab can detect mosaicism present in as few as 8% of cells; By scoring 50 cells, the lab can detect mosaicism present in as few as 5% of cells. 

• 2.      Fluorescence in situ hybridization test: This test can be completed on chromosomes or on nuclei (cells that are not in the metaphase portion of the cell cycle). As a result, this test can be completed from a blood specimen, a buccal swab (rubbing of cells from the inside of the cheek), or a skin biopsy. For this test the cells are “probed” to determine if they have a portion of chromosome 21. Given that hundreds of cells are typically scored for this test, it has the highest sensitivity for detecting mosaicism. By evaluating 100 cells, labs will be able to detect mosaicism if it is present in as few as 3% of cells; By scoring 200 cells, the lab can detect mosaicism present in as few as 2% of cells; By scoring 250 or more cells, the lab can detect mosaicism present in 1% or fewer cells.

• 3.      Microarray test: This test is completed using DNA that is extracted from cells. As a result, this test can be completed from a blood specimen, a buccal swab (rubbing of cells from the inside of the cheek), or a skin biopsy. Given that this test also involves an analysis of DNA from all chromosomes, it can identify other chromosomal findings that are present (not just Down syndrome or mosaic Down syndrome). One limitation of this test is that it cannot determine if the person has Down syndrome due to an additional structurally normal chromosome 21 or a translocation (that requires the chromosome test described above [option 1]). The presence of mosaicism that can be detected using this test will vary from lab to lab. However, using this assay, most labs can detect mosaicism that is present in as few as 4% to 10% of cells.

Can a person have mosaic Down syndrome if they received a normal chromosome test result?

   It is important to recognize that the proportion of trisomic cells can vary among tissue types. For example, there may be differences in the percentage of trisomic cells in the blood compared to the skin, heart or other organs. For this reason, one may wish to evaluate more than one type of tissue for diagnostic testing. Some people who have symptoms of mosaic Down syndrome have been diagnosed by studying a buccal specimen (but had a normal blood test result). Also, several people who have mosaic Down syndrome will have higher percentages of trisomic cells in the buccal specimen (cheek cells) compared to their blood cells. However, most people who have symptoms of mosaic Down syndrome will be successfully diagnosed from a routine chromosome test.

   The blood test to diagnose mosaic Down syndrome is widely available at nearly all chromosome testing centers. The buccal cell test is less widely available but can be ordered through several labs (for example, this test can be completed by the team at the Virginia Commonwealth University Health Molecular Cytogenetics laboratory). Your geneticists specialist team will help you locate a lab to complete this testing.

How is prenatal (before birth) testing completed to diagnose mosaic Down syndrome?

  Some women/couples elect to have information about the chromosomal make-up of an embryo (up to the 8^th week of gestation) or fetus (8^th week of gestation to term) while they are pregnant. One approach for determining if a pregnancy involves a trisomic conceptus is a screening assay called Non-Invasive Prenatal Testing (abbreviated as NIPT).  This screening test (which might also be called a cell-free DNA screening test) is performed by taking a blood specimen from a pregnant woman (at least 10 weeks' gestation). The result of this screening test identifies pregnancies that are at an increased risk for having a child with Down syndrome (or other chromosomal findings). However, since it is not a diagnostic test, it is recommended that a woman who receives a positive NIPT screen result consider a follow-up prenatal diagnostic test to determine if the fetus does indeed have trisomy 21 (or mosaicism for trisomy 21 [or another chromosomal finding]) to aid them in making decisions regarding the pregnancy.

Two types of prenatal diagnostic cytogenetic tests are available: (1) chorionic villus sampling (abbreviated as CVS), which is performed during the first trimester (typically 10 to 13 weeks' gestation); or (2) amniocentesis, which is performed during the second trimester (typically 15 to 20 weeks' gestation).  It is recommended that a woman/couple considering prenatal screening/testing receive genetic counseling to aid them in understanding the results of the tests. Also, it is important that a woman/couple who has received a result that is positive for Down syndrome or mosaic Down syndrome gain accurate information about these conditions. Genetic counselors can provide up-to-date information.  At some centers they can also connect the woman/couple with parents of a child who has Down syndrome or mosaic Down syndrome to provide opportunities for them to ask questions about life experiences related to these conditions and to enable her/them to make a decision based on accurate information.