Triploidy: Definition, Signs, Symptoms, Causes, Diagnosis, Treatment and Prognosis

Genetic and chromosomal disorders can have a variable and potentially far-reaching impact on a baby’s health.

The effects can range from mild health problems to being “incompatible with life,” which means a fatal prognosis.

Triploid syndrome, also called triploidy, is an extremely rare lethal chromosomal disorder, in which a fetus has three copies of each chromosome instead of the normal two.

If this occurs only in some cells, it is called mosaic triploidy and is less severe, which means that some cells have a normal number of 46 chromosomes and other cells have 69 chromosomes per cell.

Most cases of triploidy involve “complete” triploidy, which means that all cells in the body are affected evenly. In rare cases, triploidy can be this so-called “mosaic.”

There is some evidence that people who have mosaic triploidy may be less severely affected by the disorder than those with total triploidy. But even with mosaic triploidy, the prognosis is not good.

Humans are supposed to have 46 chromosomes (23 pairs). A person receives half of each pair of chromosomes from each parent.

Triploidy is the presence of an extra set of chromosomes in the cell for a total of 69 chromosomes instead of the normal 46 chromosomes per cell. The extra set of chromosomes originates from the father or mother during fertilization.

Triploidy can be the result of a single egg fertilized by two sperm or an error in cell division that causes the egg or sperm to have 46 chromosomes at the time of fertilization.

Babies with triploidy are usually aborted early in pregnancy. If the pregnancy continues to term, the baby dies in the first days of life or rarely survives the first six months of life.

Some affected people were reported to have survived to adulthood, but suffered from developmental delay, learning difficulties, seizures, hearing loss, and other abnormalities.

Babies affected with complete triploidy suffer from growth restriction and multiple birth defects.

Relationship with partial molar pregnancy

Some triploidy-affected pregnancies will also be affected by a partial hydatidiform mole (partial molar pregnancy), which means that there is an abnormal placenta that, in rare cases, can cause life-threatening complications for the mother.

However, not all cases of triploidy will be a molar pregnancy.

There is some suspicion that triploidy resulting from two sperm fertilizing a single egg may be more likely to cause a partial molar pregnancy than triploidy involving one egg or sperm that has 46 chromosomes from the beginning.

But this has not been proven.

Signs and symptoms

Many organ systems are affected by triploidy, but the central nervous system and skeleton are the most severely affected.

Common central nervous system defects seen in triploidy include holoprosencephaly, hydrocephalus (increased amount of cerebrospinal fluid in the brain), ventriculomegaly, Arnold-Chiari malformation, agenesis of the corpus callosum, and neural tube defects.

Babies affected with triploidy suffer from heart defects, abnormal brain development, adrenal and kidney defects (cystic kidneys), spinal cord malformations,  and abnormal facial features (widely spaced eyes, low nasal bridge, malformed ears, small jaw, small eye or absent).

Skeletal manifestations include cleft lip and palate, hypertelorism , clubfoot, and syndactyly of the fingers, the third and fourth fingers, and the second and third toes may join, and the hands may have unusual folds.

Congenital heart defects, hydronephrosis, omphalocele, and meningocele (spina bifida) are also common. There may also be liver and gallbladder defects, twisted intestines, and finger and toe deformities.

Cystic hygromas do occur but are rare. Triploid fetuses have intrauterine growth restriction that begins early in pregnancy, as early as 12 weeks, and does not affect the head as severely as the body.

Oligohydramnios (low levels of amniotic fluid) is common in triploid pregnancies.

Placental abnormalities are common in triploidy. Most often, the placenta is enlarged, may be immature, and may have cysts inside. In some cases, the placenta may be unusually small and have stopped growing.

Individuals who are mosaic will survive longer than those with complete triploidy, but generally suffer from intellectual disability, developmental delay, depression , seizures, short stature, obesity, and other abnormalities.

The pregnant mother carrying a triploid fetus sometimes experiences an increase in blood pressure ( hypertension ), swelling (edema), and excretion of albumin in the urine (albuminuria).

This condition is called toxemia or pre-eclampsia . Triploidy is frequently diagnosed in pregnancies with a cystic placenta (partial moon).

Causes of triploidy

Triploidy is the presence of an additional complete set of chromosomes. Chromosome tripling is caused by:

  • The fertilization of an egg by two sperm (60%).
  • The fertilization of an egg by a sperm that has an extra set of chromosomes (two copies of each chromosome).
  • By the fertilization of an egg that has an additional set of chromosomes (two copies of each chromosome) by a normal sperm (40%).

This disorder does not run in families and is not associated with maternal or paternal age.

Diagnosis

Triploidy can be diagnosed by genetic testing alone, that is, amniocentesis, blood tests from a newborn baby, or tissue karyotype from a pregnancy loss.

Screening tests such as the ultrasound and alpha-fetoprotein test can show warning signs of triploidy.

Triploidy may be suggested by dramatic and abnormal levels of specific maternal blood proteins, such as serum alpha-fetoprotein, human chorionic gonadotropin, estriol, and pregnancy-assisted plasma protein A, which have been associated with an increased risk of triploidy.

The presence of multiple major malformations, low amniotic fluid, and / or growth restriction on fetal ultrasound during pregnancy increases the suspicion of triploidy.

On obstetric ultrasound, abnormalities of the skeleton, central nervous system, heart, abdomen, and kidneys are visible in the most severe cases beginning at 12-14 weeks of pregnancy.

The placental abnormalities associated with a triploid pregnancy become visible at 12-14 weeks. Placecentomegaly or intrauterine growth restriction are the typical findings that warrant evaluation of triploidy, although oligohydramnios may be the first sign in some cases.

Placental enlargement is not pathognomonic for triploidy because, in some cases, the placenta becomes senescent. Triploidy must be distinguished from trisomy 13 and trisomy 18, which may appear similar on ultrasound .

But these tests cannot confirm a diagnosis of triploidy. Abnormally high hCG levels can be found in some triploidy pregnancies, and an ultrasound can show the characteristic placenta associated with a partial molar pregnancy.

As mentioned at the beginning, genetic testing allows a definitive diagnosis. Diagnosis can be made during pregnancy by chromosome analysis of cells obtained by amniocentesis or chorionic villus sampling (CVS).

The diagnosis can be confirmed after birth by chromosome analysis of tissue (skin) obtained from the affected baby. Triploidy cannot be diagnosed by chromosome microarray testing.

The accuracy of non-invasive prenatal tests using cell-free fetal DNA in the diagnosis of triploidy is still being studied.

Triploidy has been diagnosed in pregnancies that occur shortly after oral contraceptives are stopped or after long menstrual cycles.

The disorder has been reported in conceptions that occurred after in vitro fertilization and in conceptions after a history of repeated miscarriages.

Prognosis and treatment of triploidy

Most fetuses with triploidy do not survive to birth, sadly, triploidy is always fatal and there is no cure or treatment for the disease, and babies born live, most die within hours or days after birth.

As mentioned above, almost all (more than 99%) of babies with triploidy are aborted or stillborn.

A handful of babies with triploidy have lived five months or more. But these reports are rare, and generally, babies who survive the longest have mosaic triploidy, rather than full triploidy.

Affected babies generally have multiple birth defects and severe growth restriction.

Since there is no treatment for triploidy, palliative care is given if a baby survives to birth.

If triploidy is diagnosed during pregnancy, termination is often offered as an option due to additional health risks to the mother (pre-eclampsia, a life-threatening condition, or choriocarcinoma, a type of cancer).

In the event that a mother decides to continue until the end of the pregnancy or until a miscarriage occurs, doctors will closely monitor her in case any of the conditions develop.

Mosaic triploidy has an improved prognosis, but affected people have moderate to severe cognitive disabilities.

The risk of recurrence

Researchers have not found any identifiable risk factors for having a pregnancy that is affected by triploidy. Even maternal age does not appear to be a risk factor.

A small number of women can have recurrent miscarriages affected by triploidy. But in most cases, triploidy happens randomly and is a unique tragedy that does not recur in future pregnancies.

If you’ve received a triploidy diagnosis after tissue testing for miscarriage or stillbirth, the chances of it happening again are slim.

If your baby has triploidy

There is a lot of confusing information about triploidy, so if your baby has been diagnosed with this condition during pregnancy or newborn, it is likely that you are dealing with emotions, including numbness, confusion, and pain.

The first thing you need to know is that you did nothing to make this happen, and there is nothing that could have prevented it from happening. It’s okay to cry (or feel whatever else you might feel).

If your baby has been diagnosed with triploidy through amniocentesis (which is usually done between week 15 and week 20 of pregnancy), you will probably be asked if you want to continue the pregnancy.

This is an individual choice and you have to do what works for you. Some women prefer to terminate pregnancies with fatal diagnoses, while others choose to continue pregnancies, despite knowing the expected outcome.

Keep in mind that if your pregnancy is affected by a partial hydatidiform mole, there is no chance that the baby will reach term and be born alive. Your doctor will recommend discontinuation to avoid possible serious complications that could affect your health.

If the diagnosis of triploidy occurs after your baby has already been born, it is a good idea to speak with a genetic counselor about what to expect, in terms of caring for your baby.

Most of the time, the recommended treatment is to provide comfort care rather than any intensive intervention. There are numerous support groups for parents of babies with serious chromosomal disorders, and this may give you some comfort as you deal with this news.

epidemiology

Triploidy affects approximately 1-2% of pregnancies, but most miscarriages occur early in development. At birth, men with triploidy are 1.5 times more common than women; it is estimated that 2/3 of triploid pregnancies are male.