Trisomy 16 and First-Trimester Miscarriages

Trisomy 16 and Mosaic Trisomy 16 in Pregnancy

Pregnant woman with hands clasped on lap, close-up
What does it mean if trisomy 16 is the cause of a miscarriage or if mosaic trisomy 16 is found on chorionic villus sampling or amniocentesis?. PhotoAlto/Frederic Cirou/PhotoAlto Agency RF Collections/Getty Images

If you've learned that a baby you miscarried had trisomy 16, or if you're learning about the role if chromosome abnormalities in miscarriage, what do you need to know?

If, instead, you've learned that your baby may have mosaic trisomy 16 after chorionic villus sampling, an amniocentesis, or a karyotype done after birth, what do you need to know? What happens next and what does this mean over the long term?

Chromosomal Abnormalities in Miscarriage

Chromosomal disorders are the most common cause of first-trimester miscarriages, with estimates of these disorders being responsible for 50 to 75 percent of all miscarriages. Trisomies, in turn, are the most common chromosome-related finding in post-miscarriage testing.

Trisomy 16 in Miscarriage

Of all trisomies (discussed below), trisomy 16 seems to be the most common, occurring in approximately one percent of all pregnancies. and accounting for around 10 percent of miscarriages. There are different types of trisomy 16; with one type being completely incompatible with life while another may result in a healthy infant at times. We will talk about these different types, but first should explain what is meant by trisomy.

What is a Trisomy and How Do They Occur? -

Normally, people have 46 chromosomes, which are grouped together in 23 pairs.

One set of 23 chromosomes comes from the mother and the other set from the father. Most pairs (44) of the chromosomes are considered "autosomes" and the other two are "sex chromosomes." Females ordinarily have a karyotype of 46 XX and males, 46 XY.

When cells divide to form eggs and sperm in a process called meiosis, one copy of each chromosome goes to one of two eggs or two sperm.

Sometimes a mistake occurs, and two chromosomes go to one egg or sperm and none to the other.

When the sperm and egg then combine (during fertilization) the zygote will end up with either an extra chromosome (trisomy) or a missing chromosome (monosomy).

Trisomy may occur after fertilization as well. Before division the cells double their chromosomes so they have 92. When the cell divides, each daughter cell will have 46 chromosomes. If an error occurs, one cell may end up with 47 chromosomes and the other with 45.

Types of Trisomy 16

There are three types of trisomy: full, partial, and mosaic.

Full trisomy 16 - Full trisomy 16 means that all of the cells in the baby's body are affected. Full trisomy 16 is incompatible with life and nearly all babies who have the condition are miscarried in the first trimester.

Mosaic trisomy 16 - It is also possible to have mosaic trisomy 16, meaning some of the body's cells are affected while the other cells are normal. Mosaic trisomy 16 may result from the trisomy trying to correct itself during cell division very early in fetal development, leaving some cells affected but not others. Mosaicism is usually expressed as a percentage.

Partial trisomy 16 - It is also possible, in rare cases, to have a pregnancy in which the placental cells have full trisomy 16 or mosaic trisomy 16 even though the baby is chromosomally normal.

This is known as partial trisomy 16.

Understanding Karyotypes with Trisomy 16

A normal karyotype is written as 46 XX or 46 XY, with a trisomy being 47 XX or 47 XY.

Trisomy 16, is written as 47 XX +16 for a girl, or 47 XY +16 for a boy (with the +16 indicating that the trisomy involves the 16th chromosome.)

Mosaic trisomy would be written as a percentage, for example with a boy it may be written 47 XY +21/46 XY with a percentage given as to number of cells which are 47 XY +16 and the number which are 46 XY.

Diagnosis of Trisomy 16

A diagnosis of trisomy 16 may be made after a miscarriage, or in contrast, may be found during pregnancy as a result of prenatal testing.

Full trisomy 16 may be diagnosed as the cause of a miscarriage if parents collect tissue and testing for chromosomal abnormalities in a miscarriage is done.

Trisomy 16 or mosaic trisomy 16 can also be diagnosed during pregnancy through chorionic villus sampling (CVS) or amniocentesis.

What a Trisomy 16 Diagnosis After Miscarriage Means for You

Full trisomy 16 almost always results in first-trimester miscarriage. If you have been told that trisomy 16 was the cause of your miscarriage, you should know that the miscarriage was not your fault and the chances of miscarriage in a subsequent pregnancy are low. Up to 85 percent of women who have a first trimester miscarriage go on to have a normal pregnancy the next time they become pregnant.

Trisomy 16 Diagnosis Made During CVS or Amniocentesis

If you are currently pregnant and have received CVS or amniocentesis results showing cells affected by trisomy 16, it's completely normal to be scared or confused. You should know, however, that it's unlikely that the baby has full trisomy 16 if your pregnancy has progressed past the first trimester—the baby may have mosaic trisomy 16 or the trisomy may be confined to the placenta.

Mosaic Trisomy 16 During Pregnancy

Carrying a baby with mosaic trisomy 16 does carry an increased risk of complications, and it's important to see an obstetrician who specializes in high risk pregnancies to help monitor your pregnancy. Pregnancy with trisomy 16 carries a higher than average incidence of:

Congential Anomalies in Babies with Mosaic Trisomy 16 or Placental Trisomy 16

There isn't a lot of research on the outcomes for either mosaic trisomy 16 or trisomy 16 of the placenta (partial trisomy 16), but the research that is available suggests that affected babies usually do not suffer serious complications.

Among babies born with trisomy 16, the health effects can vary widely depending on the degree of mosaicism. Sometimes babies are born with no evidence of any abnormalities while others can have characteristic set of health problems. Roughly 60 percent of these children will have evidence of at least some congenital anomalies which may include:

  • Heart defects (congenital heart disease) - Ventricular septal defect is present in around 17 percent of these babies and atrial septal defect (ASD) in around 10 percent.
  • Hypospadias - Hypospadias is a condition in which the opening of the male urethra is not at the end of the penis but instead somewhere along the shaft.
  • Facial deformities such as a short neck, high forehead, and/or a pointed nose.
  • Respiratory abnormalities such as small (hypoplastic) lungs.
  • Musculoskeletal abnormalities such as scoliosis.
  • Cognitive impairment or developmental delays, but this appears to be the exception.

Long Term Outcomes of Children with Mosaic Trisomy 16

Despite complications of pregnancy and an incidence of congenital anomalies close to 60 percent, a 2017 revealed encouraging information as to the long term health of children with mosaic trisomy 16. Of school age children with trisomy 16, 80 percent were able to attend mainstream classes. Studies looking at physical health, psychological health, and quality of life were very encouraging, showing that most of these children scored between 80 and 90 on a 100 point scale of optimal quality of life.

Management of Pregnancies with Mosaic Trisomy 16

As noted above, there are several pregnancy complications which are more common with a baby with trisomy 16. Involving a perinatologist or obstetrician who specializes in high risk pregnancies is important.

Learning about the condition may help you prepare, especially learning that the majority of children born with mosaic trisomy 16 go on to have excellent physical and psychological health as they grow.

Seeing a mental health professional who is familiar with chromosomal abnormalities can be extremely helpful as well, both to reinforce the fact that there is nothing you did that caused the condition, and to help you adjust to having a child who may have some anomalies.

Learning About Trisomy 16 and Genetic Counseling  After Miscarriage

Regardless of any studies or predictions, it is normal to be upset and have questions when testing shows there may be problems with your baby. If you've learned that a baby you miscarried had trisomy 16, genetic counseling can be very helpful. Just as with carrying children with mosaic trisomy 16 is random, having a miscarriage related to trisomy 16 in the fetus is not something you caused.

Other Human Trisomies

There are many different human trisomies, some which are not compatible with life and others which are. Perhaps best known is Down syndrome (trisomy 21). As with trisomy 16, the vast majority of these trisomies are random accidents, and are unlikely to reoccur in future pregnancies.

Bottom Line on Trisomy 16, Miscarriage, and Births

With full trisomy 16, miscarriage usually occurs during first trimester, and the condition appears to be incompatible with life. While learning about this diagnosis is heartbreaking, it may be reassuring to some parents to realize that there is nothing they have done to cause the disorder, and the chance of having trisomy 16 in another pregnancy is uncommon.

With mosaic trisomy 16, the news appears to be more encouraging than thought in the past. There certainly appear to be more pregnancy complications with a fetus having trisomy 16, and there is a high incidence of congenital anomalies, but long term physical, intellectual, and psychological health of these children is usually very good.

Sources:

Coman, D., Gardner, R., Pertile, M., and P. Kannu. Trisomy 16 Mosaicism at Chornionic Villus Sampling and Amniocentesis with a Normal Physical and Intellectual Outcome. Fetal Diagnosis and Therapy. 2010. 28(2):117-8.

Chareonsirisuthigul, T., Worawishawong, S., Parinayok, R., Promosonthi, P. and B. Rerkamnuaychoke. Intrauterine Growth Retardation with Trisomy 16 Mosaicism. Case Reports in Genetics. 2014. 2014:739513.

Kliegman, Robert M., Bonita Stanton, St Geme III Joseph W., Nina Felice. Schor, Richard E. Behrman, and Waldo E. Nelson. Nelson Textbook of Pediatrics. 20th Edition. Philadelphia, PA: Elsevier, 2015. Print.

Sparks, T., Thao, K., and M. Norton. Mosaic Trisomy 16: What are the Obstetric and Long-Term Childhood Outcomes?. Genetics in Medicine. 2017 Apr 6. (Epub ahead of print).

Spencer, K., Pertile, M., Bonacquisto, L., Mills, E., Turner, S., Donalson, K., and J. Jonsson. First Trimester Detection of Trisomy 16 Using Combined Biochemical and Ultrasound Screening. Prenatal Diagnosis. 2014. 34(3):291-5.

U.S. National Library of Medicine. Genetics Home Reference. Chromosome 16. Updated 0404/17. https://ghr.nlm.nih.gov/chromosome/16#resources

Continue Reading