Overview 

The human genome consists of 46 chromosomes per cell, which makes for 23 pairs. 

Triploidy is a genetic abnormality affecting the number of the chromosomes, and is defined by the presence of 69 chromosomes per each cell. The extra chromosomes can be passed on by either of the parents during fertilisation (the conception); this can occur in 1-3% of pregnancies and usually results in miscarriage within the first trimester. It is crucial that screening and diagnosis take place as early as possible, so that the parents can make informed decisions about their pregnancy.^1,2 

In this article, we will discuss the symptoms and characteristics of triploidy and how it affects foetal development. 

Understanding triploidy

Triploidy is a rare genetic abnormality where the presence of extra chromosomes causes complications in foetal development. More specifically, triploidy cells have three sets of the same chromosome, rather than the usual two.^1,2 

Chromosomes are essential structures in the nucleus that carry our genetic information. The development of the foetus depends on the chromosomes containing functional genetic information. There are 69 chromosomes present in triploidy instead of the usual 46. The presence of extra chromosomes, as is the case in triploidy, alters the genetic blueprint for foetal development. Generally, pregnancies with triploidy are rarely carried out to term. If the baby is delivered, the infant passes away within the first day of life.^1,2 

In typical fertilisation, the egg and the sperm have one set of each chromosome, thus 23 chromosomes each – the reproductive cells are known as haploid. The fusion of a haploid egg and a haploid sperm creates a diploid cell, which has the full set of 46 chromosomes required for normal foetal development. The origin of extra chromosomes allows us to classify the different types of triploidy.^1,2

Diandric/dispermic triploidy 

There are two types of diandric triploidy that are paternal. Diandric triploidy is when the egg is fertilised by a sperm with a double set of chromosomes, thus a diploid sperm fuses with a haploid egg. Alternatively, dispermic triploidy happens when two different haploid sperm fertilise the same haploid egg, dispermic. In this case, the foetus receives two sets of chromosomes from the father and one from the mother; this results in the genotypes 69, XXX/XXY or 69, XYY. Most cases of triploidy present a paternal origin.¹

Digynic triploidy 

In this occurrence, the sperm fertilises an egg with two sets of chromosomes; therefore, the extra chromosomes come from the mother, which gives a 69, XXX or 69, XXY genotype.¹ 

Causes and risk factors 

Currently, there are no known risk factors for triploidy and it is regarded as a random genetic event. Despite many studies, no uniform pattern can be used to detect triploidy in prenatal scans. The age or genetic history of the biological parents does not contribute to the likelihood of triploidy occurrence. Due to its spontaneity, triploidy cannot be prevented. However, we do know its potential causes:^1,3

• Fertilisation: the egg is fertilised by two sperm cells or diploid sperm with a haploid egg
• Meiosis: chromosomal error during cell division of sex cells 
• Mitosis: chromosomal error during cell division in embryonic development³

Symptoms and characteristics of triploidy 

Symptoms can be identified in various stages of the pregnancy through the foetus and the placenta. The type of triploidy determines which symptoms are observed. 

Symptoms during pregnancy 

In an ultrasound scan, triploidy can be identified through abnormal findings. These include visible growth restrictions in the foetus’ limbs and brain. Oligohydramnios can be a consequence of triploidy because there are low levels of amniotic fluid in the womb. Furthermore, abnormal placenta tissue can develop, associated with a partial hydatidiform mole; this mole describes cystic tissue that can grow as a result of triploidy. Unfortunately, the combination of factors results in miscarriage. If the pregnancy continues into the third trimester, then stillbirth usually follows.³

Physical characteristics of the foetus 

There are some characteristics that can indicate triploidy:^3,4 

• Severe intrauterine growth impairment 
• Deformities in the fingers and toes, such as the 3rd and 4th fingers becoming united 
• Short neck 
• Neural tube defects: a spinal cord abnormality
• Abnormal facial features: widely spaced eyes, absent or small eyes, low nasal bridge, cleft lip, low-set malformed ears
• Skull defects, such as increased size of the head (macrocephaly) 
• Congenital (existing at, or before birth) heart defects^3,4 

Placental abnormalities 

Different types of triploidy have different impacts on the placenta. At 10-14 weeks, a diandric pregnancy will have an enlarged placenta and a partial mole in the tissue; this is paired with a symmetrical, growth-stunted foetus. In contrast, a digynic triploidy will have a very small, non-molar placenta with a stunted, asymmetrical foetus.⁴ 

The placental growth does not affect the manifestation of other symptoms experienced by the foetus, such as heart and skull defects. However, there is an interesting link between the parental origin of triploidy and the impact on the growth of the foetus through changes in the placenta; a correlation was found in mice embryos, and human embryos are being explored.⁴ It is hypothesised that the differences in growth between the foetuses are mediated through placental characteristics. 

Diagnostic methods

Scans and blood tests are the first line of identification for triploidy. The presence of abnormalities in the formation of the foetus and low amniotic fluid are further indicators of triploidy. In initial scans, these concerns prompt the testing for triploidy.⁵ 

Chromosome analysis is carried out through amniocentesis; in this procedure, a needle is inserted into the uterus through the abdomen and extracts amniotic fluid for analysis. The position of the foetus is identified to avoid harm being inflicted by the needle. Alternatively, chorionic villus sampling (CVS) can be done and requires taking a small tissue sample from the placenta for analysis.⁵ 

Both of these methods allow for karyotyping (chromosome analysis). During karyotyping, the shape and size of chromosomes are examined. The chromosomes are isolated and arranged in numerical order. Karyotyping is essential in identifying the extra chromosomes present in triploidy.⁵

Additionally, maternal blood can be used for triploidy diagnosis. Abnormal levels of alpha-fetoprotein, estriol, and pregnancy-associated plasma protein-A (PAPP-A) are blood markers that indicate triploidy.⁵

Prognosis and management

Pregnancies that suffer from triploidy have a poor survival rate. It is rare for a pregnancy to be carried to term. If the foetus reaches the gestation period, there is a low chance of live birth. For babies that survive delivery, their lifespan is short, usually no longer than a day. All these outcomes are tragic for the parents. They suffer emotionally and psychologically. As a result, the parents having a child pregnancy with triploidy need support through this difficult process.⁶

Parents face an almost impossible decision: whether or not to continue with the pregnancy; this is an extremely complex and personal decision that requires the consideration of several factors. Life-threatening complications can develop for the birth parent, such as pre-eclampsia, which results in high blood protein in the urine. A genetic counsellor ensures the parents are made aware of all practical possibilities to allow for informed decisions to be made; however, making this decision can be very isolating and difficult. Therefore, experts must be present to ensure the parents feel fully supported and comfortable with their choice.^2,3,5

Summary

• Triploidy is a severe chromosomal abnormality where the foetus has three copies of each chromosome in every cell of their body
• They have a total of 69 chromosomes, rather than the usual 46 chromosomes
• Triploidy occurs due to complications in fertilisation.
  • Dispermic triploidy: two sperm cells fertilise one haploid egg 
  • Diandric: a diploid sperm fertilizes a haploid egg
  • Digynic: a diploid egg is fertilised by haploid sperm
• These genetic errors generally cause foetal fatality
• Triploidy presents unusual ultrasound findings, such as severe growth restrictions, placenta deformations, and limb abnormalities
• The birth parent could experience pregnancy complications, such as preeclampsia 
• There are prenatal tests, including CVS, amniocentesis, that identify irregularities in the DNA of the foetus
• Due to the high mortality rate, support and close monitoring of the well-being of the parents is the best management for triploidy