Triploidy

Triploidy is a chromosomal abnormality characterized by an extra set of chromosomes in all cells of the body. Typically, each cell receives one set of chromosomes from each parent, totaling to two sets of chromosomes, or 46 chromosomes. In triploidy, individuals have three sets of chromosomes or 69 total chromosomes. There are two types of triploidy based on parental origin. Maternal-origin triploidy occurs as a result of the egg failing to undergo proper meiosis (i.e., chromosomal reduction to 23 chromosomes), which results in a diploid gamete (i.e., a sex cell containing 46 chromosomes). In contrast, paternal-origin triploidy occurs when two sperm cells, instead of one, fertilize an egg. Triploidy is rare and occurs in approximately 1 in 10,000 live births. Generally speaking, triploid pregnancies are not compatible with life and account for approximately 20% of spontaneous abortions. 

In triploidy, there are three sets of chromosomes (i.e., 69 chromosomes total) in each of the cells of the body, whereas in trisomy, there is an extra copy of one chromosome (i.e., 47 chromosomes total). The most common trisomy chromosomal abnormalities are trisomy 21 (i.e., Down syndrome), trisomy 18 (i.e., Edwards syndrome), and trisomy 13 (i.e., Patau syndrome). The number refers to the specific chromosome in which the extra chromosome exists. For example, in trisomy 21, there is an additional chromosome 21, or three total. Trisomy syndromes may present with similar clinical features including upward-slanting eyes, intellectual disability, low-set ears, congenital heart defects, and cleft lip or palate. Individuals with trisomy 21 may live relatively long lives, whereas trisomy 18 and trisomy 13 often lead to severe developmental abnormalities and shortened life expectancy. Similarly, triploidies often result in spontaneous abortions, or severe birth defects and growth restriction that are incompatible with survival.

Triploidy typically occurs during fertilization, a reproductive process where sperm fertilize an egg cell. Normally, gametes or reproductive cells (i.e., sperm and egg) are haploid, which means they contain a single set of unpaired chromosomes (i.e., 23 chromosomes). During fertilization, the haploid nuclei of both gametes come together to form a diploid zygote (i.e., a new diploid organism consisting of a pair of chromosomes, one from each gamete). 

Triploidy may occur if an egg is fertilized by two sperm cells, instead of one. This results in two haploid sets of chromosomes from the sperm cells, and one haploid set from the egg (i.e., 69 total chromosomes). This can lead to a partial hydatidiform mole which is a non-viable molar pregnancy (i.e., a  tumor that develops in the uterus instead of a fetus). Triploidy may also occur if there is an error in meiosis during sex cell formation, where chromosomes fail to produce haploid gametes. For example, if a diploid sperm fertilizes a normal haploid egg cell, or if a diploid egg is fertilized by haploid sperm the resulting zygote would be triploid.

In rare cases, triploidy may occur after the fertilization process. Mosaic triploidy refers to errors in mitosis (i.e., cell division) during embryonic development. While the mechanisms are poorly understood, mosaic triploidy involves abnormal mitotic cell divisions, which result in certain cells having an extra set of chromosomes (i.e., triploid) and other cells having a normal set of chromosomes (i.e., diploid). Therefore, cells resemble a “mosaic,” as there are two genetically distinct cell types. 

Early signs of triploidy may include an enlarged placenta, intrauterine growth restriction, small size for gestational age, polyhydramnios (i.e., excess amniotic fluid), and structural defects, which are all findings that can be detected via ultrasound during prenatal visits. Often, these abnormalities lead to early spontaneous abortions or miscarriages. Rarely, the fetus may survive until term delivery with severe birth defects incompatible with life. These include unusual facial features like cleft lip and palate, congenital heart defects, underdeveloped kidneys and lungs, and severe intellectual disability.

Diagnosis of triploidy begins with a thorough review of symptoms and medical history. In the prenatal period, routine imaging with ultrasound can help assess fetal growth development and structural or placental abnormalities. Maternal serum screening, like alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) as well as cell-free DNA testing (i.e., a blood test that analyzes cell-free DNA of the placenta) may be offered in the first trimester of pregnancy to assess for chromosomal abnormalities. 

The diagnosis is often confirmed with more invasive testing methods including chorionic villus sampling (i.e., a needle is inserted into the womb and a sample of cells is taken from the chorionic villi of the placenta) and amniocentesis (i.e., a sample of cells is taken from amniotic fluid, fluid that is directly surrounding the fetus). The samples are then further analyzed via karyotyping, which is a process that pairs and orders all the chromosomes within an organism, to assess for an additional set or pair of chromosomes. Chorionic villus sampling is often done at 10 to 13 weeks gestation, whereas amniocentesis is done at 15 to 18 weeks gestation. These testing methods have high diagnostic accuracy but carry a 0.5% to 1% risk of miscarriage, therefore counseling is often provided before the procedures.

Because triploidy is incompatible with life, treatment consists of pre or postnatal counseling and support for the family, as well as palliative care measures for the newborn, if they survive the pregnancy. If triploidy is detected in the early trimesters, an individual may choose to terminate the pregnancy medically, with mifepristone and misoprostol, or surgically (e.g., suction curettage, dilation, and evacuation). Palliative care measures for the newborn may include hydration with intravenous fluids and respiratory support (e.g., oxygen). Genetic counseling and support should be provided to the parents and family members to better understand the genetic basis of triploidy and the risks of future pregnancies.

Triploidy is a chromosomal abnormality characterized by an extra set of chromosomes, resulting in a higher number of chromosomes in all cells of the body. In triploidy, there are three sets of chromosomes to total 69 chromosomes, whereas in trisomy, there is an extra copy of one chromosome, which totals 47 chromosomes. Triploidy typically occurs during fertilization, a reproductive process where sperm fertilize an egg cell. A triploidy pregnancy results in spontaneous abortion, or severe birth defects and growth restriction that are incompatible with life. Diagnosis is confirmed with either chorionic villus sampling or amniocentesis. Treatment is aimed at palliative care for the newborn and extensive counseling and support for the family members.