Introduction

Definition of triploidy

Triploidy is a chromosome abnormality that is brought on when each cell has an additional set of chromosomes. Triploidy occurs when a cell has 69 chromosomes rather than the normal number of chromosomes (46). This additional pair of chromosomes comes during fertilisation, from the mother or the father.¹ In addition to causing a number of congenital growth problems, the syndrome typically results in miscarriages or early infant deaths.²

Signs and symptoms

Early in pregnancy, the majority of fetuses with triploidy spontaneously miscarry. If the pregnancy continues to term, the infant dies during the first days of life. The symptoms and indicators of full triploidy in infants are as follows:

• Growth delay
• Birth abnormalities, which include:
  • Macrocephaly, which means increased head size
  • Heart abnormalities
  • Brain defects
  • Adrenal glands abnormalities
  • Neural tube malformations
  • Cystic kidneys
  • Facial differences include cleft lip and palate, tiny jaw, absent or small eyes, low nasal bridge, low-set deformed ears, and widely spread eyes
  • Finger and toe deformities (hands may have odd simian creases, and the hands' third and fourth fingers and feet's second and third toes may be combined)
  • Defects in the liver
  • Defects in the gallbladder short neck
  • Defects in genitalia, intestines twisted¹

Importance of studying triploidy

Miscarriages in triploid pregnancies typically occur early in the pregnancy. The baby passes away in the first few days of life if the pregnancy goes to term. Numerous birth abnormalities and growth limits are present in infants with full triploidy. According to reports, a small number of affected people lived to adulthood but suffered from hearing loss, seizures, difficulties with learning, developmental delays, and other abnormalities.¹

It is key to know about triploidy in genetic counselling as it provides reliable information and support to the families it touches. Genetic helpers can guide future moms and dads to get the causes, like errors in fertilisation and the risks of it happening again, which are often small.

Incidence of triploidy

It is thought that between 1% and 3% of all conceptions are triploid.³ But only 0.002% of pregnancies at 16-20 weeks are triploid, which is a lot less than the ones that make it to the second part of pregnancy. This is because most of these pregnancies end in an early loss. In fact, it’s rare for triploidy to let the growth of the embryo reach the second part of the pregnancy.⁴ About 20% of embryos conceived through normal in vitro fertilisation (IVF) are triploid. When triploid babies survive to birth, they have many issues and have several abnormalities and die not long after birth.³

Increased maternal age is not a risk factor for triploidy, unlike nondisjunction-related aneuploidies, and no additional susceptibility factor has been found yet. Consequently, little has been understood about the process behind triploidy.⁴

Prevalence of triploidy

During pregnancy

According to estimates, approximately 1 in 4800 pregnancies are expected to develop triploidy at 11–13 weeks of gestation, and the prevalence drops to less than 1 in 27,000 in the second trimester. The few instances that survive to the third trimester (possibly mosaic or chimeric) usually result in stillbirth or death of the infant.⁵

At live birth

In all live births, the frequency of this chromosome abnormality is extremely low (1/20–50,000), although it is higher (1/5,000) in newborns with very low birth weight (0.02%). More than 66% of all incidences of triploidy are male pregnancies.³

Detection of triploidy in prenatal screenings

An early prenatal diagnosis of triploidy may be hindered by the lack of a consistent and clear clinical pattern linked to the condition. Actually, a wide range of phenotypic characteristics have been reported in triploid pregnancies, such as placental alterations, variations in the amount of amniotic fluid, fetal growth restriction, increased nuchal translucency (NT), and a variety of defects affecting the face, heart, limbs, urinary tract, and central nervous system. However, the most frequently reported fetal malformation is syndactyly, but it is a non-pathognomonic finding.⁴

Mechanisms leading to triploidy

Triploidy happens when fetal cells contain an extra set of chromosomes. The total number of chromosomes in triploid cells is 69 rather than the 46 seen in normal cells. This extra set of chromosomes is caused by an error in fertilisation. This may be from:

• Dispermy, this happens when the egg is fertilised by two sperm
• Meiotic errors in the genome this happens when the egg is fertilised by a sperm that has an extra set of chromosomes or when the sperm fertilises an egg with an extra set of chromosomes

Triploidy typically occurs rarely or at random and is unrelated to either the age of the birthing parent or a family history.^1,2

Type of triploidy

According to the size of the placenta and the origin of the extra chromosome set, which may come from the father or mother, triploidy can be classified as:

• Type I, which is known as Diandric, in which the extra chromosome set is of paternal origin. The fetus has an enlarged placenta, a normal or microcephalic head, and a moderate growth delay
• Type II, which is known as Digynic in this type, the extra chromosome set is of maternal origin. The fetus has a small placenta and is severely growth restricted with pronounced wasting of the body and sparing of the head¹

Diagnosis and detection

The suspicion of triploidy is raised by the observation of multiple significant abnormalities, little amniotic fluid, and/or growth restriction on fetal ultrasound throughout pregnancy.

During pregnancy

The diagnosis can be made during pregnancy by chromosome analysis (karyotyping) of cells obtained by amniocentesis or chorionic villus sampling (CVS).¹

After delivery

Triploidy can be confirmed after birth by chromosome examination of tissue (skin) taken from the affected infant. The accuracy of non-invasive prenatal testing using cell-free fetal (cff) DNA in the diagnosis of triploidy is still being investigated.¹

Maternal serum screening

Abnormal levels of certain maternal blood proteins, such as alpha-fetoprotein, human chorionic gonadotropin, estriol, and pregnancy-associated plasma protein-A, have been linked to a higher risk for triploidy.¹

Challenges in diagnosis

Conventional maternal serum biochemical examinations in the first and second trimesters of pregnancy can aid in screening for triploid pregnancies. However, the growing use of cell-free DNA (cfDNA) based non-invasive prenatal testing (NIPT) for autosomal trisomies, sex chromosome abnormalities, and other imbalances is leading to a decrease in the use of serum testing in some countries. Because there is no proportional variation in the quantity of DNA fragments over the various autosomes, counting-based NIPT approaches can not regularly diagnose triploidy.⁵

Clinical implications of triploidy

Miscarriages in triploid pregnancies usually happen at the beginning of the pregnancy. The baby passes away in the first few days of life if the pregnancy goes to term. Complete triploidy causes growth limitation and a number of birth abnormalities in infants. According to reports, a small number of individuals with the condition lived to adulthood but suffered from loss of hearing, seizures, learning disabilities, developmental delays, and various other anomalies.

For the mother who is pregnant with a triploid fetus, she can suffer from preeclampsia or toxaemia, which has the signs and symptoms of oedema, elevated blood pressure, and albuminuria, or the secretion of albumin in the urine.¹

Summary

Triploidy is a rare and significant chromosome abnormality with an extra set of chromosomes, making a total of 69 chromosomes instead of the normal 46 chromosomes. It shows up in about 1-3% of all conceptions, but very few make it to birth due to a high rate of early loss in pregnancy. This condition arises from aberrations in fertilisation, such as dispermy (two sperm fertilise the egg) or meiotic errors that add an extra chromosome set in the egg or sperm. If the extra set of chromosomes comes from the mother or the father, triploidy may cause growth abnormalities and placental problems.

Ultrasound and DNA tests before birth are key to finding triploidy early in pregnancy. Yet, since this issue often leads to death, most cases end as miscarriage or stillbirth, and live births rarely live past a few days. Knowing about triploidy helps with genetic counselling and helps families make informed reproductive choices. Continued research and advancements in prenatal screening will improve detection, support affected families, and enhance medical management strategies.