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What Is Trisomy 18?
Trisomy 18 is a condition caused by a problem in your chromosomes. It's also called Edwards syndrome, after the doctor who first described it.
Chromosomes are the threadlike structures in cells that hold genes. Genes carry the instructions needed to make every part of a baby's body.
Trisomy 18 is a condition where you have three copies of chromosome 18 in your body's cells instead of two. (Photo Credit: KATERYNA KON/Science Source)
When an egg and sperm join and form an embryo, their chromosomes combine. Each baby gets 23 chromosomes from the mother's egg and 23 chromosomes from the father's sperm – 46 in total.
Sometimes the mother's egg or the father's sperm contains the wrong number of chromosomes. As the egg and sperm combine, this mistake is passed on to the baby.
A "trisomy" means that the baby has an extra chromosome in some or all of the body's cells. In the case of trisomy 18, the baby has three copies of chromosome 18. This causes many of the baby's organs to develop in an abnormal way.
Types of trisomy 18
There are three types of trisomy 18:
Trisomy 18 is the second-most common type of trisomy syndrome, after trisomy 21 (Down syndrome). About 1 in every 5,000 babies are born with trisomy 18, and most are female.
The condition is even more common than that, but many babies with trisomy 18 don't survive past the second or third trimester of pregnancy.
Babies with trisomy 18 are often born very small and frail. They typically have many serious health problems and physical defects, including:
The risk of having a child with trisomy 18 increases with the age of the mother, though women of any age can have a child with trisomy 18. There isn't anything you can do to lessen your chances of having a child with the condition as it's due to a chromosome disorder.
If you've had one baby with trisomy 18, the risk of having another with it is 0.5% to 1%. If you or your partner is a carrier of a chromosome disorder that leads to partial trisomy 18, the risk of having another child with this condition could be as high as 20%.
The doctor usually will do a screening test using some of the mother's blood. The test can't say for sure if your baby will have trisomy 18, but it can tell if your baby is at risk for it – and for other diseases that come from chromosome errors.
To diagnose trisomy 18, your doctor will take cells from the amniotic fluid (amniocentesis) or placenta (chorionic villus sampling) and analyze their chromosomes. These tests are done after the screening test because they carry a small risk of miscarriage or early labor.
Chorionic villus sampling (CVS) is done in the first trimester, and amniocentesis is done in the second or third trimester.
Trisomy 18 ultrasound
Around 12 weeks of pregnancy or later, your doctor can do an ultrasound, which will give them a picture of what your fetus looks like. It may tell them if your baby has trisomy 18, but it's usually confirmed by the CVS or amniocentesis.
Some of the things a doctor may see on an ultrasound if your baby has trisomy 18 include a smaller size, problems with the intestines, and problems with the limbs, like clenched fists.
After birth, the doctor may suspect trisomy 18 based on your child's face and body. A blood sample can be taken to look for the chromosome disorder.
The chromosome blood test can also help determine how likely you are to have another baby with trisomy 18. If you're concerned that your baby may be at risk for trisomy 18 because of a past pregnancy, you may want to see a genetic counselor.
There is no cure for trisomy 18. Treatment for trisomy 18 consists of supportive medical care to provide the child with the best quality of life possible. This might include:
At one time, babies born with trisomy 18 were not resuscitated at birth because their long-term chances of survival were so low. Now, guidelines have changed, and reviving infants with trisomy 18 is more likely to be done. The Textbook of Neonatal Resuscitation has removed trisomy 18 from the list of diagnoses that it considers ethical to not resuscitate at birth.
Because trisomy 18 causes such serious physical defects, many babies with the condition don't survive to birth. About half of babies who are carried full-term are stillborn. Boys with trisomy 18 are more likely to be stillborn than girls.
Of those babies who do survive, half die within the first week of life. Fewer than 10% live to reach their first birthday. Children who do live past that milestone often have severe health problems that require a large amount of care. Only a very small number of people with this condition live into their 20s or 30s.
Having a child with trisomy 18 can sometimes be emotionally overwhelming, and it's important for parents to get support during this difficult time. Organizations such as the Chromosome 18 Registry & Research Society and the Trisomy 18 Foundation can help.
Trisomy 13 is another chromosomal condition. It's sometimes called Patau syndrome, after the doctor who first described it.
In this condition, the person has three copies of chromosome 13, instead of two. Most of the time, all the cells in the body have three copies of chromosome 13, but as with trisomy 18, there are rarer types where an extra chromosome 13 gets attached to another chromosome (translocation) or only some of the body cells have the extra copy of chromosome 13 (mosaic trisomy 13).
Babies with trisomy 13 generally have severe medical issues and birth defects, including:
Trisomy 13 affects 1 in 16,000 babies, though most fetuses with this condition don't survive to the third trimester of pregnancy. Most babies born with this condition die within the first few days or weeks of life, as they have so many medical complications. Just 5% to 10% make it past their first year.
Like trisomy 18, no one knows why some babies get this condition. It's known that the chance increases with the mother's age, though women of any age can have a child with trisomy 13. About 80% of babies with trisomy 18 or 13 are born to mothers under 35. The condition can be diagnosed before birth with the same tests used to identify trisomy 18, or after birth by a physical examination.
Trisomy 18 is a condition where you have three copies of each chromosome 18 in your body's cells instead of two. This can lead to serious physical and mental disabilities. There is no cure, though treatment can include surgeries, medicines, breathing tubes, and feeding tubes. Some parents opt just for comfort care. Life expectancy is usually a year or less.
How old is the oldest living person with trisomy 18?
The oldest people were reported to be in their early 40s a few years ago. But it's unclear if they are alive today.
Are babies with trisomy 18 less active in the womb?
Yes, they are often less active.
Windows On The Womb
Windows on the WombSelect any one of the techniques listed below to find out more about it. The weeks during which doctors commonly use such techniques are listed with each technique.
Enhanced Alpha FetoproteinAmniocentesisChorionic Villus SamplingDoppler deviceFetal EchocardiographyUltrafast fetal MRINuchal Translucency TestUltrasound scanning
Enhanced Alpha Fetoprotein or the Quad (AFP)15 to 18 weeks A protein produced by the baby's liver, alpha fetoprotein (AFP) normally enters the mother's bloodstream. In this test, blood drawn from the mother is examined for AFP; the amount of AFP in her blood determines the level of risk for disorders such as Down syndrome, neural-tube defects, abdominal-wall defects, and Edwards syndrome. High levels may mean a neural-tube defect or that some or all of the baby's brain material is missing. A low level can be an indication of Down syndrome. Because this is a screening test, showing only the baby's level of risk, follow-up testing for an abnormal level is recommended. There is no risk to the baby, but because as many as 5 percent of all women test positive, further testing often results. The vast majority of these women turn out to carry healthy fetuses.Amniocentesis16 to 18 weeks Obstetricians typically recommend the use of amniocentesis for women more likely to be carrying a baby with abnormalities, such as older women (35 and above) or women with a family history of genetic diseases. An ultrasound prior to the test determines the baby's location, and then a specialist uses a small needle to withdraw about a tablespoon of the amniotic fluid surrounding the baby. Cells from the baby found floating in the fluid are cultured and examined to look for chromosomal disorders. Doctors use the test primarily to detect spina bifida or Down syndrome, but also Rh disease, fetal anemia, sickle-cell anemia, and to determine the baby's sex. Late in pregnancy, doctors use amniocentesis to find out if the baby's lungs are sufficiently developed and thus able to withstand, if necessary, a medically required premature birth. The U.S. Centers for Disease Control and Prevention estimates that the rate of miscarriage following amniocentesis is between one in 200 to 400 procedures.Chorionic Villus Sampling (CVS)10.5 to 13 weeks As with amniocentesis, obstetricians may suggest using CVS, short for chorionic villus sampling, to detect genetic disorders such as Down Syndrome. In CVS, specialists perform an ultrasound to determine the position of the fetus and then remove fetal tissue by placing an instrument through the cervix or abdomen. Unlike amniocentesis, which can also detect Down syndrome, this test can be carried out much earlier in pregnancy, and test results are also available sooner. That means that if parents decide to terminate a pregnancy based on the results, they can do so as much as nine weeks earlier than in the case of amniocentesis, creating fewer risks to the mother's health. There is a 1 to 2 percent risk of miscarriage following the procedure.Doppler device6 weeks to term A Doppler device is a small, portable machine that uses ultrasound waves to detect and magnify the baby's heartbeat. Doctors use this test during most office visits to verify that the baby is alive. After about the tenth week, a baby's heart rate can vary between 120 and 170 beats per minute. In the third trimester, obstetricians may use a variation of this test, known as umbilical cord Doppler, to examine the flow of nutrients between heartbeats, to ensure that the baby is receiving adequate nourishment. There is no known risk to the baby or the mother with this test.Fetal Echocardiography14 weeks to term This test is essentially a very detailed ultrasound focussing on the structure and function of the heart. Doctors use it only when either siblings or parents have a history of heart defects, when other tests such as amniocentesis have produced abnormal results, when the mother has diseases that can affect the heart (such as diabetes or phenylketonuria), or when the fetus has been exposed to certain drugs. Most experts conduct the test between the 20th and 22nd week to ensure that they can see the heart clearly. There is no known risk to the baby or mother with this test.Ultrafast fetal MRIsecond or third trimester MRI (magnetic resonance imaging) relies on a magnetic field and radio waves to "eavesdrop" on the body's electromagnetic transmissions. An MRI image can clarify the diagnosis of a fetal abnormality observed in an ultrasound and better prepare parents and their doctors for any interventions that may be needed to help the baby before or immediately after birth. It is especially helpful for examining certain tissues, such as the brain, that are encased in bone and would be difficult or impossible to see using ultrasound. MRI is not as widely available as ultrasound. It poses no known risk to the baby or mother.Nuchal Translucency Test (NT Scan)11 to 14 weeks This test uses ultrasound to examine the fold of skin on the back of the baby's neck. At this early stage of development, the skin is so thin that fluid accumulates between it and the underlying structures. More fluid, which produces a thicker fold, can be a sign that the baby has a chromosomal abnormality, such as Down syndrome. This test is available at a number of university medical centers around the U.S. As with ultrasound, there is no known risk to the baby or mother.Ultrasound scanning5 weeks to term Many women will have at least one ultrasound during their pregnancy. High frequency sound waves are directed at the fetus and the returning "echoes" form a live-action picture of the baby. Typically performed between 16 and 18 weeks, an ultrasound provides a general check of the baby's anatomy and can also help to date the pregnancy. Later on in pregnancy, ultrasound can gauge the baby's growth and development, determine the location of the placenta, and measure the amount of amniotic fluid. Three-dimensional ultrasounds, which are now becoming available at some health centers, provide a much clearer, more photographic image and make it possible to observe the baby from any angle, regardless of what position the baby is in during the procedure. There is no known risk to the baby or mother.Windows on the Womb—Glossary
Down syndrome—In most cases caused by a third chromosome 21, Down syndrome results in mental retardation and other abnormalities. Children with Down syndrome have a widely recognized characteristic appearance.Neural-tube defects—An NTD occurs in the neural tube, the part of the fetus that becomes the brain or spinal cord. NTDs result in the partial or complete absence of the brain, or in an opening of the spine. They are among the most common of all serious birth defects.
Abdominal-wall defects—Abdominal-wall defects feature a soft bulge of tissue or a small, localized swelling on the abdomen, most often caused by a hernia. A hernia is an area where muscles are weak enough to allow internal organs to protrude.
Edwards syndrome—Also known as trisomy 18, Edwards syndrome is associated with a third chromosome 18, which causes multiple physical abnormalities and severe mental retardation. Few infants survive beyond their first year.
Rh disease—When the baby is Rh-positive and the mother is Rh-negative, the mother's antibodies can cross the placenta and attack the baby's red blood cells, resulting in jaundice, anemia, brain damage, heart failure and death. Rh disease occurs only when the mother has previously been sensitized to Rh-positive red blood cells and has developed antibodies to them.
Fetal anemia—Fetal anemia occurs primarily when the mother's blood type is incompatible with the baby's, leading to the destruction of red blood cells in the baby's blood. This in turn results in an oxygen deficiency for the baby.
Sickle-cell anemia—In this chronic inherited disease, the normally round red blood cells become sickle- or crescent-shaped. When these abnormally shaped cells move through small blood vessels they can clog blood flow or break apart, causing sudden severe pain in many areas of the body, damage, or anemia.
Diabetes—Diabetes is a life-long disease in which the body produces too little insulin or is unable to use the insulin properly. The result can be dangerously high blood-sugar levels, which, when untreated, starve cells of energy and over time can damage the eyes, kidneys, nerves or heart.
Phenylketonuria—Phenylketonuria is a rare genetic disorder in which the body is unable to properly metabolize the amino acid phenylalanine, one of the eight essential amino acids found in protein-containing foods. The accumulation of phenylalanine in the blood and body tissues can cause severe mental retardation and developmental delays if not treated.
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Ancient DNA Reveals Down Syndrome In Historical Populations
Researchers from the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) have developed a method that integrates data from genetic screening, osteological and archeological analyses to explore trisomies in historic and prehistoric populations.
Trisomies are genetic disorders characterized by the presence of an additional chromosome in a person's cells. Typically, each human has 23 pairs of chromosomes or 46 in total. Individuals with trisomies possess a total of 47.
By screening the genomes of ~10,000 ancient individuals, the research team identified genetic evidence for 6 cases of trisomy 21 – Down Syndrome – and 1 case of trisomy 18 – Edwards Syndrome – in infant remains that date back as far as 5,000 years ago.
The study offers novel insights into how these genetic conditions were perceived in the past, as some of the children's remains were accompanied by special objects, indicating they were loved and cherished, the authors said.
"I like that we can look back on the past and see a positive aspect of our ancestors, and hopefully see ourselves in that," said Dr. Adam "Ben" Rohrlach, a mathematician with joint affiliations at the University of Adelaide and MPI-EVA, and first author of the study.
The research is published in Nature Communications.
The field of ancient DNA analysis is thrivingThe number of studies analyzing ancient DNA (aDNA) has substantially increased since the field emerged in 1984. Large databases comprising thousands of genomes mean that, today, we know more about the origin of humans, the migration patterns of our ancestors and how they battled ancient epidemics than ever before.
Only recently has the data published by the field become so vast that researchers could use it to explore the incidence of uncommon conditions. Rohrlach and colleagues' study is the first systematic genetic screening and osteological description of autosomal trisomies.
It's perhaps a more unique application of aDNA analysis, but one that Rohrlach views as worthwhile: "We know more about diseases that have affected large groups of people, such as plague, but individual disease and disorder is more personal, because it potentially marks a single, specific person as 'different'. So, I think we're all interested in how our ancestors approached these situations," he said.
Down Syndrome in past societiesSequencing data collected between 2016–2022 at MPI-EVA was screened for trisomy using the team's new method. This approach can be applied to any laboratory's data, Rohrlach explained: "Our method compares the amount of DNA in a sample that comes from each chromosome and compares it to the average that is observed in all of the other samples (looking for when a 50% increase is observed)."
Of the 9,855 prehistoric and historic genomes analyzed, 6 infants presented with a high number of DNA sequences from chromosome 21, indicating that they had Down Syndrome. While there isn't a single bone marker available for trisomies, where possible, Rohrlach and team recorded pathological lesions from the skeletal remains of these children that were preserved. They observed porosity in the cranial bones for almost all samples. While this is sometimes seen in Down Syndrome, the researchers stress that it can also be caused by other health conditions.
What is Down Syndrome?Down Syndrome is a genetic condition where an individual has an extra copy of chromosome 21. This extra genetic material impacts the body and brain, resulting in physical and developmental symptoms that can range from moderate to severe.
Five of the children's remains were found across Bronze Age settlement sites in Greece and Bulgaria, and Iron Age settlement sites in Spain. They are estimated to be 2,500–5,000 years old.
"All of the Bronze Age or Iron Age burials were intramural burials, indicating that these infants were considered worthy of deserving a burial place inside of the dwellings," the authors said.
One child, buried in Lazarides in Greece, wore a necklace made up of different colored beads. Another, in Spain, was surrounded by the complete remains of sheep and goats. Her grave also featured bronze rings and a Mediterranean seashell.
The remaining child was buried in a former church graveyard in Finland between the 17th and 18th century. He was found in a wooden coffin, wearing clothes that contained bronze pins and decorative bronze flowers, a trend in this period.
"For us, we interpret this as an indication that these children were loved and cherished like any child today," Rohrlach expressed. "I cannot imagine another reason that the baby at Lazarides was buried with a beautiful necklace. Unfortunately, we can't know exactly."
Want more breaking news?Subscribe to Technology Networks' daily newsletter, delivering breaking science news straight to your inbox every day.
Subscribe for FREEWhile advancements in medicine mean that people with Down Syndrome can live long, fulfilled lives, this wasn't always the case historically. Combined evidence suggests that only two of the six children survived postnatally.
"These syndromes can cause a number of symptoms and complications which medicine at the time could not overcome," Rohrlach said. "However, it is not clear how the children at the Iron Age sites were chosen for intramural burial, and the burials of many other children at these sites were found that did not indicate a diagnosis of trisomy 21. It is possible that these people were burying children if they were stillborn, and this would skew the number of perinatal cases."
Edwards Syndrome in Iron Age SpainRemains from a child with three copies of chromosome 18 were also identified at one the of the Spanish Iron Age sites. This is characteristic of Edwards Syndrome, a genetic condition that is rarer than Down Syndrome and affects the development of the brain and organs.
"At the moment, we cannot say why we find so many cases at these sites," said Roberto Risch, an archeologist at the Autonomous University of Barcelona, and study co-author. "But we know that they belonged to the few children who received the privilege to be buried inside the houses after death. This already is a hint that they were perceived as special babies."
Prevalence rates for autosomal trisomies were historically lower than current rates, according to the study. There are many factors that likely contribute to this finding, according to Rohrlach: "One could be that we know from modern cases that an increase in the rate of prevalence is correlated with an increase in the age of the mother, and potentially mothers were younger in past societies."
Sampling bias might also play a role. Burials can be hard to find, and the easiest gravesites to miss are likely those belonging to younger individuals. In reality, the prevalence of autosomal trisomies might be higher than calculated in the study because these graves have not yet been discovered.
Refining aDNA screening methods to detect rare disordersThe team at MPI-EVA is keen for aDNA screening methods to be better refined, enabling more accurate detection of genetic conditions such as autosomal trisomies. "A complete extra copy of a chromosome is a very easy signal to observe," Rohrlach said. "Other conditions are much more subtle and may only affect a part of the chromosome, or even a single gene. Hence, we need to develop and refine these methods to detect these more subtle variations that can still have significant effects."
Unfortunately, the team was not able to access all of the skeletons from which the genetic data had been obtained, as they came from previous studies. "It would have been nice to have been able to revisit some more of the osteological questions that we had as this angle could have helped osteologist to flag potential cases in their records and museum collections," Rohrlach said.
That being said, he ultimately "feels happy" that the research team were able to publish a study with a positive message. "I'm also proud that this study shows the potential of cross-disciplinary research, and how a mathematician, and computer scientist and an osteologist can come together to produce a meaningful narrative highlighting the lives of these babies, and those that were around them," Rohrlach concluded.
Dr. Adam "Ben" Rohrlach was speaking to Molly Campbell, Senior Science Writer for Technology Networks.
About the interviewee:
Dr. Adam "Ben" Rohrlach is a postdoctoral researcher at the Max Planck Institute for the Science of Human History in Jena, Germany. His areas of interest are bioinformatics, phylogenetics, population genetics and biostatistics, with a focus on human history.
Reference: Rohrlach AB, Rivollat M, de-Miguel-Ibáñez P, et al. Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA. Nat Comms. 2024. Doi: 10.1038/s41467-024-45438-1
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