Introduction

DNA is a molecule that carries our genetic information. It’s like a blueprint that determines our traits, from eye colour to our predisposition to certain diseases. DNA is present in every cell of our body, packed into tiny structures called chromosomes. Normally, we inherit 2 sets of chromosomes at the time of fertilisation, 23 chromosomes from our mother (via the egg) and 23 from our father (via the sperm).¹ 

However, in 2–3% of pregnancies, an extra set of 23 chromosomes is inherited from either the mother or the father.¹ This condition is known as triploidy, a rare chromosomal abnormality in which cells have 69 chromosomes instead of the normal 46 chromosomes per cell. Triploid pregnancies usually result in a miscarriage.² However, if pregnancy reaches completion, the baby only survives for a short duration of time due to developmental abnormalities.³ This article explores the causes of triploidy, focusing on fertilisation errors and chromosomal abnormalities.

Causes of triploidy

Triploidy can occur due to errors during fertilisation of the egg by the sperm or later during the development of a multicelled embryo from a single-celled zygote.^4,5

Fertilisation errors

Diandry

The condition in which the egg is fertilised by a sperm containing 46 chromosomes, resulting in a zygote with 69 chromosomes.

Dispermy

The condition in which two sperm, each with 23 chromosomes, fertilise the egg, resulting in a zygote with 69 chromosomes.

In both diandry and dispermy, the zygote has two sets of chromosomes from the father and a single set from the mother.

Digyny

The condition in which egg-producing cells fail to divide properly, resulting in an egg cell with 46 chromosomes instead of the normal 23. When this egg is fertilised by a normal sperm containing 23 chromosomes, the resulting zygote ends up with 69 chromosomes. 

Chromosomal abnormalities

Post-fertilisation errors

In some cases, fertilisation results in a normal zygote of 46 chromosomes, but triploidy still occurs due to improper chromosome separation as the zygote divides to become a multicelled embryo.⁵

In normal fertilisation, a sperm (with 23 chromosomes) successfully fertilises an egg (with 23 chromosomes), resulting in a zygote with the expected 46 chromosomes (2 sets).⁵

The zygote undergoes its first cell division (mitosis) in which ideally, the 46 chromosomes should duplicate and then separate evenly, resulting in two daughter cells, each with 46 chromosomes.⁵

This is where the problem usually occurs with triploidy. During this first cell division, the chromosomes fail to separate correctly. This is called nondisjunction. Here, one daughter cell receives all 46 chromosomes (both sets), while the other daughter cell receives none.⁵

The cell with 46 chromosomes then continues to divide. However, because it has already missed a proper chromosome separation, some of its descendant cells will end up with three sets of chromosomes (69 chromosomes). This happens because the initial error during cell division is propagated as the embryo continues to grow.⁵

This scenario often results in mosaic triploidy. This means that the embryo will have a mix of cells: some cells will have the normal 46 chromosomes, while other cells will have 69 chromosomes (triploidy). The severity of the condition depends on the proportion of triploid cells in the developing embryo.⁵

Nondisjunction is more frequent during meiosis (the creation of eggs and sperm) than during the early mitotic divisions of the zygote. That's why triploidy is more often caused by errors in egg or sperm formation, but it can happen after fertilisation, leading to mosaic triploidy.⁵

Genetic mutations

While the immediate cause of triploidy is the presence of an extra set of chromosomes, the underlying reason for this extra set can sometimes be traced back to genetic mutations. It’s crucial to understand that these mutations are usually not inherited from the parents, but they typically arise randomly during the formation of the egg or sperm, or very early in embryonic development.⁶

Meiosis is the cell division process that creates eggs and sperm, each with half the number of chromosomes as regular cells. Mutations in genes that control meiosis can disrupt this process. This can lead to eggs or sperm with an extra set of chromosomes.⁶

Some mutations might even make it more likely for an egg to be fertilised by two sperm (dispermy), which would directly result in a triploid zygote. However, the specific genes involved in the predisposition of dispermy are not well-established.⁶

As these mutations occur spontaneously and are not passed down from parents, it means that having one child with triploidy does not necessarily increase the risk of having another child with the same condition. The exact genetic factors that contribute to triploidy are still being researched.⁶

Effects of triploidy

Triploidy can result in:²

• Miscarriage: This is a common outcome.
• Stillbirth: This occurs when triploidy occurs in later stages of pregnancy.
• Severe birth defects, such as fused fingers, abnormal lung development, facial dysmorphia, cardiac, renal and neurological dysfunction.

Diagnosis and detection

Triploidy can be diagnosed through:²

• Ultrasound scans: They can show developmental abnormalities.
• Karyotyping: This is a test which examines chromosomes in a given sample of cells. It can confirm the presence of extra chromosomes.
• Non-invasive prenatal testing (NIPT): This is a test in which small fragments of the fetus's DNA circulating in the mother's bloodstream are analysed to detect chromosomal abnormalities like triploidy.

Summary

Triploidy is a rare chromosomal disorder in which an individual has 69 chromosomes instead of the normal 46. It occurs in about 2–3% of pregnancies and often results in miscarriage or stillbirth due to severe developmental abnormalities.

The condition arises due to errors during fertilisation or early embryonic development. Fertilisation errors can occur in several ways, such as diandry, digyny or dispermy. Triploidy can also result from errors after fertilisation during early cell division. Normally, the zygote divides to produce cells with identical chromosome sets. However, in some cases, chromosomes fail to separate properly, leading to mosaic triploidy, where some cells have 69 chromosomes while others have the typical 46. This type of triploidy can vary in severity depending on the proportion of affected cells.

In some cases, genetic mutations affecting the process of meiosis—the cell division that produces sperm and egg cells—can contribute to triploidy. These mutations may cause errors in chromosome separation, leading to eggs or sperm with an extra set of chromosomes. Some mutations might even increase the likelihood of dispermy, but the specific genes involved are not well understood. Since these mutations arise spontaneously and are not inherited, having one pregnancy affected by triploidy does not necessarily increase the risk of future occurrences.

Triploidy typically leads to miscarriage, stillbirth, or severe congenital abnormalities affecting the heart, lungs, brain, and other organs. Diagnosis is possible through ultrasound scans, karyotyping (a test that examines chromosomes in cells), and non-invasive prenatal testing (NIPT), which analyses fetal DNA in the mother's blood to detect chromosomal abnormalities.