[Explained by a Doctor] What Is Trisomy Detected by NIPT?

Revised: January 27, 2026

This article provides a physician-supervised, in-depth explanation of the basics of Trisomy 21, 18, and 13 as detected by NIPT, including how they occur, their relationship with maternal age, and the accuracy and limitations of testing.

Many pregnant women considering NIPT feel anxious about the word "trisomy." Even after receiving an explanation at a medical institution, the content is often highly technical, and many people struggle to fully understand it before deciding whether to undergo testing.

Trisomy is a condition in which the number of chromosomes changes. NIPT primarily detects three types: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome). It is important to correctly understand exactly what these conditions involve and how accurate the testing is.

In this article, we explain trisomy in an easy-to-understand way from a physician's perspective, based on evidence from academic papers both in Japan and abroad. We comprehensively cover the mechanisms behind trisomy, its relationship with maternal age, and the accuracy and limitations of NIPT detection, so that with correct knowledge you and your family can make the best choice for you.

Basics of Trisomy – What Is a Change in Chromosome Number?

The normal chromosome makeup

Human cells normally contain 46 chromosomes, forming 23 pairs. Of these, 22 pairs are autosomes and 1 pair is the sex chromosomes (XX or XY). Chromosomes are packed with genetic information and function as the blueprint for our bodies.

A chromosome is a structure in which DNA (deoxyribonucleic acid) is tightly wound around proteins called histones. Each chromosome contains hundreds to thousands of genes, which direct protein synthesis and thereby control every function of the body. By inheriting 23 chromosomes from the father and 23 from the mother, we receive half of our genetic information from each parent [ref:7].

What is trisomy?

Trisomy refers to a condition in which a specific chromosome that should normally exist in two copies is instead present in three copies. "Tri" means "three," and "somy" is a medical term meaning "chromosome." In other words, instead of 46 chromosomes, there are 47.

Conversely, a condition in which a chromosome that should be present in two copies exists in only one copy is called "monosomy." Trisomy and monosomy are collectively referred to as "aneuploidy," representing abnormalities in chromosome number. In trisomy, the genes on the extra chromosome are overexpressed, which can affect development and bodily function in various ways. However, the extent and severity of this impact varies greatly depending on which chromosome is affected.

The mechanism behind trisomy

Most cases of trisomy arise from an error in chromosome distribution (nondisjunction) during the formation of eggs or sperm (meiosis).
Normally, during meiosis chromosomes separate accurately so that eggs and sperm each end up with 23 chromosomes. However, if a chromosome pair fails to separate properly during this process, one resulting cell may receive 24 chromosomes and the other 22. When an egg or sperm carrying 24 chromosomes is fertilized, the resulting embryo has 47 chromosomes.

Nondisjunction can occur at either of two main stages: when homologous chromosomes fail to separate during the first meiotic division, or when sister chromatids fail to separate during the second meiotic division. Studies show that about 75% of Trisomy 21 cases originate from errors in the first meiotic division, most of which occur during egg formation in the mother [ref:1]. In rare cases, nondisjunction can also occur after fertilization, during cell division (mitosis) in the body's somatic cells, resulting in a condition known as "mosaic trisomy."

Differences between full, translocation, and mosaic types

There are several types of trisomy, each differing in how it arises and in its clinical characteristics.

• Full (complete) trisomy: The most common type, in which a specific chromosome is present in three copies in every cell. About 95% of Trisomy 21 cases fall into this category [ref:2].
• Translocation trisomy: A type in which part or all of the extra chromosome is attached (translocated) to another chromosome. About 3-4% of Trisomy 21 cases are of this type, and if a parent carries a balanced translocation, the risk of recurrence in a future pregnancy may be higher [ref:2].
• Mosaic trisomy: A type in which only some cells in the body have trisomy while the rest have a normal chromosome count. This accounts for about 1-2% of Trisomy 21 cases and is generally associated with milder symptoms than the full type.

The link with maternal age

It is well known that the frequency of trisomy is strongly correlated with maternal age.
The risk rises markedly, especially from age 35 onward. This is thought to be because meiotic errors become more likely as eggs age [ref:1]. For example, the incidence of Trisomy 21 (Down syndrome) is about 1 in 2,000 in mothers aged 20, rising to about 1 in 365 at age 35 and about 1 in 100 at age 40 [ref:2].

Recent research has shown that one mechanism behind the increase in meiotic errors with maternal aging is the deterioration, with age, of a protein called "cohesin," which is important for correctly separating chromosomes [ref:7]. As cohesin function declines, chromosome separation becomes unstable, making nondisjunction more likely. The association between maternal age and trisomy risk is seen not only in Trisomy 21 but similarly in Trisomy 18 and Trisomy 13.

Not all trisomies result in live birth

In theory, trisomy can occur in any chromosome, but most trisomies severely affect fetal development and result in early miscarriage.
Trisomies that survive to birth are mainly limited to chromosomes 13, 18, and 21, as well as the sex chromosomes. This is thought to be because these chromosomes are relatively small and contain fewer genes, so their impact on survival is comparatively smaller than that of other chromosomes.

Indeed, chromosomal analysis of miscarriage tissue most commonly reveals Trisomy 16, yet Trisomy 16 never results in a live birth. Similarly, trisomy involving large chromosomes such as 1 or 2 almost always results in early miscarriage when it occurs. Chromosomal abnormalities are found in about 50% of all miscarriages, with trisomy accounting for the largest share [ref:8].

The 3 Main Trisomies Detectable by NIPT

NIPT primarily targets three autosomal trisomies for detection. Here we explain the characteristics and clinical significance of each.

Trisomy 21 (Down syndrome)

A condition in which chromosome 21 is present in three copies, this is the most common trisomy, occurring in about 1 in 700 live births [ref:2].
Characteristic facial features, low muscle tone, congenital heart disease, and delayed intellectual development are commonly seen, though the degree varies greatly between individuals. Congenital heart disease occurs in about 40-50% of patients, most often atrial or ventricular septal defects. Hypothyroidism, gastrointestinal obstruction, and visual or hearing impairment may also co-occur, but early detection and appropriate treatment can address many of these symptoms [ref:2].

Thanks to advances in medical care and rehabilitation, life expectancy has increased remarkably over recent decades. In the 1980s, average life expectancy was about 25 years; today it exceeds 60 years. Some individuals live into their 80s [ref:2], and many people with Down syndrome live in their communities. Participation in early intervention programs and educational support has also expanded opportunities for social participation.

Trisomy 18 (Edwards syndrome)

A condition in which chromosome 18 is present in three copies, occurring in about 1 in 6,000 live births [ref:3].
It is accompanied by serious heart disease, digestive system abnormalities, and underdevelopment of the central nervous system, and miscarriage is also common. Even when diagnosed during pregnancy, a substantial proportion of cases end in miscarriage or stillbirth before birth. Infants who are born show characteristic physical features such as a distinctive hand posture (overlapping fingers), micrognathia (small jaw), a prominent back of the head, and rocker-bottom feet.

About 50% of infants born with the condition die within the first week of life, and over 90% die by age one, according to reports [ref:3], though advances in medical technology in recent years have led to reports of longer-term survival. In particular, cases where surgical treatment of heart disease is possible may see extended survival. However, treatment decisions require thorough discussion between the family and the medical team.

Trisomy 13 (Patau syndrome)

A condition in which chromosome 13 is present in three copies, occurring in about 1 in 10,000 live births [ref:4].
It is accompanied by serious brain malformations such as holoprosencephaly, cleft lip and palate, polydactyly, and severe heart disease. Holoprosencephaly is a condition in which the forebrain fails to divide properly, also causing various abnormalities in the midline of the face. Underdevelopment of the eyes (microphthalmia or anophthalmia) is also frequently observed.

As with Trisomy 18, the prognosis is severe: about 80% die within the first month of life, and over 90% die by age one, according to reports [ref:4]. In mosaic cases, symptoms may be milder than in the full type, and longer-term survival has been reported in some cases.

Sex Chromosome Trisomies and Rare Trisomies

Sex chromosome trisomies

NIPT can also detect trisomies involving the sex chromosomes (X and Y chromosomes). Representative examples include XXX (Triple X syndrome), XXY (Klinefelter syndrome), and XYY syndrome.
Compared with autosomal trisomies, these tend to have a milder physical and intellectual impact, and many people go through life without ever being diagnosed.

• Triple X syndrome (47,XXX): Occurs in females, at a frequency of about 1 in 1,000. In most cases, physical appearance does not differ from that of other women, though some individuals may be taller than average or have mild learning difficulties.
• Klinefelter syndrome (47,XXY): Occurs in males, at a frequency of about 1 in 500-1,000. Delayed puberty, infertility, and mild learning difficulties have been reported, but with hormone therapy and appropriate support, many individuals lead ordinary social lives.
• XYY syndrome (47,XYY): Occurs in males, at a frequency of about 1 in 1,000. There is a tendency toward slightly taller stature, but otherwise few notable physical symptoms are seen, and most individuals lead lives no different from the general population.

Sex chromosome trisomies generally have a better prognosis than autosomal trisomies, and with appropriate medical support and educational accommodations, a high quality of life is entirely achievable. However, NIPT's detection accuracy for sex chromosome abnormalities is sometimes somewhat lower than for autosomal trisomies, so results should be interpreted with care [ref:5].

Rare trisomies detected by NIPT

Expanded versions of NIPT available in recent years can also detect autosomal trisomies (rare trisomies) other than those involving chromosomes 13, 18, and 21. However, these rare trisomies rarely result in a live birth, and if detected, the possibility of confined placental mosaicism must be considered. If a rare trisomy is detected, it is important to consult with a medical specialist through genetic counseling regarding its clinical significance and appropriate next steps [ref:9].

＼Find out your risk for Down syndrome and sex chromosome conditions／

Accuracy and Limitations of Trisomy Detection by NIPT

How NIPT basically works

NIPT analyzes fetal-derived cell-free DNA (cfDNA) circulating in the mother's blood. During pregnancy, as placental chorionic villi cells break down, DNA fragments are released into the mother's bloodstream. Of this total cfDNA, the fetal-derived portion (the fetal fraction) is typically around 10-20%, and this ratio has a major effect on test accuracy [ref:6]. Using next-generation sequencing technology, the amount of cfDNA originating from each chromosome is measured, and trisomy is suspected when the amount of DNA from a particular chromosome is statistically higher than expected.

Detection accuracy for the 3 major trisomies

Trisomy 21 (Down syndrome) is reported to have the highest detection accuracy with NIPT.
A review combining multiple large-scale studies reports sensitivity of over 99% and specificity of over 99.9%, indicating a level of accuracy close to virtually error-free [ref:5].

Trisomy 18 (Edwards syndrome) has also been reported to have very high accuracy, though sensitivity is slightly lower than for Trisomy 21, at around 97.9%.
Even so, specificity remains above 99%, and the reliability of results is well maintained [ref:5].

Trisomy 13 (Patau syndrome) is reported to have both sensitivity and specificity above 99%, but is characterized by somewhat greater variability between studies [ref:5].
For this reason, testing accuracy is considered to have somewhat more room for improvement compared with Trisomy 21 and Trisomy 18. Chromosome 13 has an uneven GC content (the ratio of guanine and cytosine in the DNA sequence), which tends to introduce bias during sequencing — one reason for the variability in accuracy.

Understanding positive predictive value and false positives

Even when a test's sensitivity and specificity are high, the "positive predictive value" (PPV) can vary greatly depending on maternal age and disease prevalence. PPV refers to the probability that a condition is truly present when the test result is positive.

For example, for a condition with relatively high prevalence such as Trisomy 21, the PPV in mothers aged 35 and older can reach 80-90% or more, whereas for a condition with lower prevalence such as Trisomy 13, the PPV may be only around 50%. In other words, a positive NIPT result does not necessarily mean the condition is truly present. Understanding this point correctly is very important for avoiding unnecessary anxiety [ref:5].

NIPT is a "non-diagnostic" test

NIPT is a highly accurate screening test, but it is not a diagnostic test. If a positive result is obtained, a confirmatory chromosomal test such as amniocentesis or chorionic villus sampling is necessary.
These tests directly collect fetal cells to examine the chromosomes, allowing for a definitive diagnosis. Amniocentesis is generally performed around 15-18 weeks of pregnancy, and chorionic villus sampling around 10-13 weeks. Because these invasive tests carry a small risk of miscarriage (about 0.1-0.3%), whether to undergo them requires careful consideration [ref:9].

Limitations of NIPT

There are chromosomal abnormalities that NIPT cannot detect. Balanced translocations, in which chromosomes are rearranged without a change in total amount, and some cases of mosaicism, in which only some cells carry the abnormality, are difficult to detect. Because a balanced translocation involves no change in DNA quantity, it is in principle undetectable by NIPT, which relies on quantitative analysis of cfDNA.

In recent years, some NIPT tests have also become able to detect certain microdeletion syndromes, but not all microscopic chromosomal abnormalities can be covered, and the scope varies by test. The detection accuracy for microdeletions is generally lower than for the three major trisomies, and the false-positive rate tends to be higher, so results require more careful interpretation.

In addition, test accuracy is known to decrease under certain conditions, such as twin pregnancy or maternal obesity [ref:6]. Maternal obesity can lower the fetal fraction in cfDNA, meaning an insufficient amount of fetal-derived DNA may be obtained. In rare cases, "confined placental mosaicism" (CPM), in which the chromosomal makeup of the placenta differs from that of the fetus, can also cause false positives or false negatives. Because NIPT strictly analyzes cfDNA derived from the placenta rather than the fetus itself, it can be affected by confined placental mosaicism.

What to Know Before Undergoing NIPT

The best timing for testing

NIPT is generally available from 10 weeks of pregnancy onward. Before 10 weeks, the fetal fraction in maternal blood has not yet increased sufficiently, making it harder to obtain accurate results. It is important to discuss the appropriate timing for testing with your obstetrician.

The process from testing to receiving results

1. Receive counseling or an explanation at the medical institution and provide consent for testing.
2. A blood sample is drawn from the mother (usually about 10-20 mL, involving very minimal physical burden).
3. cfDNA is extracted from the collected blood and analyzed using next-generation sequencing.
4. The analysis results are reported (results are typically available in about 1-2 weeks).
5. Based on the results, genetic counseling or a confirmatory test is considered as needed.

The importance of genetic counseling

Undergoing genetic counseling, both before and after NIPT, is strongly recommended [ref:9]. In genetic counseling, a specialist provides a detailed explanation of the purpose, method, accuracy, and limitations of the test, helping you correctly understand the meaning of your results. It is especially important to discuss next steps thoroughly with a medical specialist if a positive result is obtained or if the test is inconclusive (test failure).

The Japan Society of Obstetrics and Gynecology also emphasizes the importance of establishing an appropriate counseling system when implementing NIPT [ref:9].

Understand Trisomy Correctly and Make the Best Choice

Trisomy is a numerical chromosomal abnormality in which a specific chromosome is present in three copies, and NIPT can detect the three main types — Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome) — with high accuracy. The sensitivity and specificity of the test are very high, and it is well established as a useful screening test.

However, NIPT is only a screening test, not a diagnostic one. Even if a positive result is obtained, there is a possibility of a false positive, so a confirmatory test such as amniocentesis is necessary. It is also important to understand that there are chromosomal abnormalities that NIPT cannot detect.

Interpreting test results requires counseling from a specialist who takes maternal age and individual risk factors into account. Whether to undergo testing, and how to interpret the results, differs depending on each family's values and circumstances. What matters most is thinking things through carefully based on accurate knowledge and making a choice you feel at peace with. At seeDNA Genetic Medical Institute, our specialist staff are ready to carefully support you with any concerns or questions about testing, so please feel free to contact us.

＼Find out your risk for Down syndrome and sex chromosome conditions／

Frequently Asked Questions

Q1. How does trisomy occur?

A. Most cases of trisomy arise from an error in chromosome distribution (nondisjunction) during the formation of eggs or sperm (meiosis). An egg or sperm that would normally have 23 chromosomes ends up with 24, and after fertilization an embryo with 47 chromosomes is formed. This error is known to become more frequent as maternal age increases [ref:1].

Q2. From what point in pregnancy can NIPT be performed?

A. NIPT is generally available from 10 weeks of pregnancy onward. Before 10 weeks, fetal-derived cfDNA (fetal fraction) in maternal blood has not yet reached a sufficient level, which may prevent accurate results. Please consult your obstetrician about the specific timing of testing.

Q3. If NIPT comes back positive, does that definitely mean trisomy?

A. No. NIPT is a screening test, not a diagnostic test. Even if a positive result is obtained, there is a possibility of a false positive, so a confirmatory test such as amniocentesis or chorionic villus sampling must be performed. For conditions with lower prevalence, such as Trisomy 13, the positive predictive value can be relatively low [ref:5].

Q4. What is the average life expectancy for someone with Trisomy 21 (Down syndrome)?

A. Thanks to advances in medical care and rehabilitation, the average life expectancy of people with Down syndrome has increased significantly. It was about 25 years in the 1980s but now exceeds 60 years. Some cases of survival into the 80s have been reported, and many people live in their communities [ref:2].

Q5. Are there chromosomal abnormalities that NIPT cannot detect?

A. Yes, there are. Balanced translocations (rearrangements of chromosome segments with no change in total amount) and some cases of mosaicism are difficult to detect. Not all microdeletion syndromes can be detected either, and the scope covered varies by test. It is important to understand the limitations of NIPT and consider additional testing as needed [ref:6].

Q6. How do sex chromosome trisomies differ from autosomal trisomies?

A. Sex chromosome trisomies (Triple X syndrome, Klinefelter syndrome, XYY syndrome, etc.) generally have a milder physical and intellectual impact compared with autosomal trisomies. Many people go through life without ever being diagnosed. With appropriate medical support and educational accommodations, leading an ordinary social life is entirely possible.

Q7. How long does it take to receive test results?

A. NIPT results are generally available about 1-2 weeks after the blood draw. This may vary slightly depending on the testing facility and test type, so please contact seeDNA Genetic Medical Institute for details.

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