General: Trisomy 18 is a genetic disease caused by the presence of an additional copy (or part of an additional copy) of chromosome 18. Normal individuals have two copies of chromosome 18, people with trisomy 18 have three copies (or part of an additional third copy) of chromosome 18 present.
The genes inside human chromosomes control the growth, development, and functions of the body. The additional genetic material from an extra chromosome 18 disrupts normal development and causes symptoms of trisomy 18. However, researchers have not discovered exactly how this extra genetic material leads to this disorder.
Most cases of trisomy 18 are not inherited and are due to a nondisjunction error in the eggs, sperm, or embryo.
Random error: The third copy of chromosome 18 may result from an error during the formation of the reproductive cells (either eggs or sperm). Eggs and sperm are generated through cell divisions, and if an error called nondisjunction occurs during these cell divisions, the sperm or egg may carry an extra copy of chromosome 18. A nondisjunction error involves an improper separation of chromosomes when a cell divides.
Trisomy 18 may also result from a nondisjunction error during cell division early in fetal development. If this is the case, some cells in the affected individual will contain the normal number of chromosome 18, but some cells will contain an additional copy. This condition is called mosaic trisomy 18.
Translocation: Another way trisomy 18 can be caused is through a genetic error called a translocation. A translocation occurs when part of one chromosome becomes fused to another chromosome. In trisomy 18, part of chromosome 18 could become fused to another chromosome. Although the individual in whom the translocation occurs may actually be unaffected by the disorder, offspring of this individual may inherit additional chromosome 18 material from the fused chromosome and could be affected with trisomy 18. This is a rare event, and most cases of trisomy 18 do not result from inheriting a translocation.
General: There are tests that can be used to check for trisomy 18. Screening tests during pregnancy can indicate a risk for trisomy 18. If screening tests are positive, prenatal diagnostic tests may be recommended. Diagnostic tests are more conclusive, and provide an answer as to whether or not trisomy 18 is actually present. Screening and diagnostic tests are generally performed during pregnancy, but they are also available after birth.
Alpha-fetoprotein (AFP) testing: Alpha-fetoprotein (AFP) testing, also called triple screen testing, is a screening test that is performed on the mother's blood, usually between the 15th and 17th week of pregnancy. This test checks for the presence of three substances: AFP, human chorionic gonadotropin (hCG), and estriol. These substances tend to be low in pregnancies affected with trisomy 18. AFP is a protein secreted by the fetal liver, and hCG and estriol are both hormones secreted by the fetus. Because this is a screening test, it does not always accurately predict the presence of trisomy 18.
Ultrasound: Ultrasound is a type of non-invasive screening test in which sound waves are used to take images of the embryo within the mother's body. If specific markers on the embryo are observed during this testing, there may be an increased risk of trisomy 18. However, if only one marker associated with trisomy 18 is observed, chances are unlikely that trisomy 18 is present. Some specific markers that are associated with trisomy 18 and are used for this test include clenched hands, choroid plexus cysts, rocker bottom feet, delayed growth, heart defects, kidney abnormalities, omphalocele (an abdominal wall defect), esophageal atresia, and polyhydramnios (excess amniotic fluid).
Chorionic villus sampling (CVS): Chorionic villus sampling (CVS) is a prenatal diagnostic test that can be used to diagnose trisomy 18. During CVS, a small amount of the chorionic villi, which is a tissue that attaches the pregnancy sac to the wall of the uterus, is taken. The sample is then analyzed to determine if an additional copy of chromosome 18 is present. CVS is typically performed about 10-12 weeks after the mother's last menstrual period. There is a risk of miscarriage associated with this diagnostic test.
Amniocentesis: Amniocentesis is another method that can be used to diagnose trisomy 18. It is typically performed later in the pregnancy than CVS, at about 15-18 weeks. In amniocentesis, a needle is inserted into the uterus, and a small amount of fluid from the sac surrounding the fetus is removed. The sample is then analyzed to determine if an additional copy of chromosome 18 is present. As with CVS, a risk of miscarriage is associated with amniocentesis.
Trisomy 18 can also be detected after pregnancy, by checking for physical signs or symptoms, and by performing genetic testing to check for an additional third copy of chromosome 18 in the cells of the newborn.
Chromosome studies: If trisomy 18 is suspected after birth, a karyotype test is performed to confirm a diagnosis. This test provides a picture of the person's chromosomes. A sample of the patient's blood is taken and analyzed for the presence of an extra chromosome 18. This test analyzes at least 20 cells because patients with mosaic trisomy 18 may only have the extra chromosome in some cells. If an extra chromosome 18 is detected, a positive diagnosis is made. In some cases, low-level mosaicism may be missed. Therefore, if the initial test results are negative, but trisomy 18 is strongly suspected, a repeat test may be performed.
signs and symptoms
Symptoms may vary from individual to individual, and there is no way to know with certainty what specific symptoms trisomy 18 will cause.
Trisomy 18 is associated with a high level of mortality. Only 50% of newborns with trisomy 18 live past the first week of life, and only 5%-10% of newborns with trisomy 18 live past one year of age, due to a wide range of developmental defects. A small number of children may survive to the teenage years, but will likely have serious medical problems.
An unusually large uterus, extra amniotic fluid, and a smaller placenta than normal may all be observed during pregnancy if trisomy 18 is present in the fetus.
Trisomy 18 is associated with a number of different developmental defects and abnormalities, including low birth weight, a small head or jaw, low-set ears, a cleft lip and palate, hearing loss, mental retardation, heart defects, kidney problems, eye defects (such as a hole or split in the iris), a small pelvis with limited hip movement, esophageal atresia (a defect in the connection of the esophagus to the stomach), omphalocele (protusion of the intestine through the belly button), underdeveloped fingernails, delayed growth, and other developmental delays. Males with trisomy 18 may have undescended testes.
Due to these defects, babies with trisomy 18 may have problems feeding, breathing, and gaining weight. Trisomy 18 also often leads to constipation.
Other symptoms may include seizures, increased muscle tone, and clenched hands with second and fifth fingers on top of the others.
Heart defects: Trisomy 18 may lead to a number of defects in the heart and the circulation of blood. These include ventricular septal defect (VSD), atrial septal defect (ASD), and patent ductus arteriosus (PDA). In VSD, there are holes in the walls of the heart, and in ASD, the walls of the heart do not close properly. In PDA, a blood vessel, called the ductus arteriosus, does not close properly, which may lead to problems with the circulation of blood. Heart problems associated with trisomy 18 may be severe and often contribute to mortality in trisomy 18 patients.
Infections: Trisomy 18 leads to an increased risk of infections, including urinary tract infections, ear infections, eye infections, and upper respiratory tract infections. In some cases, these infection may be severe and life threatening.
Kidney defects: Several problems with the kidney can arise from trisomy 18, including the growth of cysts on the kidney, hydronephrosis (the swelling of a kidney due to urine backup), and horseshoe kidney (an abnormal fusion of the kidneys). Kidney defects vary in severity and may be life threatening in some cases.
Malnutrition: Babies with trisomy 18 may have difficulty feeding and/or malformed digestive tracts. As a result, some infants may not receive adequate nutrition.
Maternal age: Women who are older than the age of 35 have an increased risk of having a child with trisomy 18. This is because as women age, there is a greater chance that the cells in her eggs will not divide properly. As a result, mutations are more likely to occur in the genetic makeup of her eggs.
Parental genetic makeup: People who have a type of genetic error, called a translocation, may have a higher risk of having children with trisomy 18. These individuals often have the normal number of copies of chromosome 18, but inside their cells, a part of chromosome 18 has become fused to a different chromosome. Because these individuals have the normal number of copies of chromosome 18, they may not be affected with trisomy 18. However, offspring of these individuals may inherit additional chromosome 18 material from the fused chromosome and could be affected with trisomy 18.