In the cell, genetic material is contained in discrete units of deoxyribonucleic acid (DNA) called chromosomes. Normal human cells contain 23 pairs of chromosomes - 22 pairs of non-sex chromosomes (autosomes) and one pair of sex chromosomes. Trisomies are genetic abnormalities where instead of a normal pair of chromosomes, three copies of a chromosome are present. Trisomies can occur in either sex chromosomes or autosomes.
Trisomy 13 is a severe and often lethal genetic disorder that occurs in individuals who carry three copies of chromosome 13 in their cells. Trisomy 13 is the third most common autosomal trisomy in newborns, after Down's syndrome (trisomy 21) and Edwards' syndrome (trisomy 18). It is estimated that trisomy 13 occurs in 0.02-0.005% of newborns, or one out of every 5,000-20,000 live births.
Thomas Bartholin first described the developmental defects that are typical of trisomy 13 in 1656. However, the underlying genetic cause was not discovered until 1960, when Klaus Patau characterized the trisomic nature of the disease. Thus, trisomy 13 is sometimes called Patau syndrome, Bartholin-Patau syndrome, or 13+ syndrome.
A significant proportion of trisomy 13 pregnancies end in spontaneous abortion (miscarriage) or stillbirth. Of the trisomy 13 live births, the median survival time is 7-10 days, and the vast majority (90-95%) of affected patients die within one year. Survival times of up to 10 years have been reported for trisomy 13 patients, although these cases are extremely rare.
The presence of an extra chromosome often results in death before birth, usually in the early stages of pregnancy. However, some trisomic embryos (e.g. trisomy 21, trisomy 18, trisomy 13, and trisomy X) may survive to birth. Of the human trisomies that can yield live births, trisomy 13 generally exhibits the most severe birth defects.
Trisomy 13 is most often caused by random events during the division of egg or sperm cells (called meiosis), which can result in an egg or sperm cell with extra copies of chromosome 13. Random errors may also occur in the division of cells in the embryo (called mitosis), leading to a condition known as mosaic trisomy 13 or mosaic Patau. In mosaic individuals, some (but not all) cells in the body carry extra copies of chromosome 13. Like full trisomy 13, mosaic trisomy 13 is not considered to be inheritable.
In rare cases, a portion (or all) of chromosome 13 attaches, or translocates, to another chromosome, resulting in an inheritable form called translocation trisomy 13. Carriers of chromosome 13 translocations may have balanced translocations, in which the amount of genetic material from chromosome 13 is preserved. Therefore, these individuals may display no symptoms of trisomy 13 but have increased risks of producing children with excess amounts of chromosome 13.
Because of the high rate of spontaneous abortion and the poor prognosis for trisomy 13 patients, early prenatal diagnosis may be particularly important for prospective parents. Counseling is also important, especially for parents who carry chromosome 13 translocations, so that they may make informed decisions regarding the potential risks associated with carrying and caring for children with trisomy 13.
Maternal age: The occurrence of meiotic non-disjunction, or the failure of chromosomes to separate properly during meiosis, increases with maternal age. Therefore, older women have increased risks of bearing children with trisomy 13. Of the mothers who give birth to babies with trisomy 13, the average age is 31.
Genetic carriers: Individuals with translocations involving chromosome 13 may give birth to children with trisomy 13. It has been reported that parental origin may determine the risk for inheriting translocation trisomies, with maternal translocations having a greater frequency of inheritance than paternal translocations.
Predisposition to meiotic non-disjunction: It has been suggested that some mothers may be predisposed to meiotic non-disjunction, and have increased risks of bearing children with trisomies. Women who have previously had trisomy 21 pregnancies are at a slight (but statistically significant) risk of having further trisomic pregnancies. Occurrences of trisomy 21 and either trisomy 13 or 18 have been reported in the same family.
Other factors: Race and gender appear to be determinants of longevity in trisomy 13 patients, with non-white females having higher median survival times. It has also been suggested that maternal obesity and gestational diabetes may increase the risks of trisomy 13, but these claims are not supported by conclusive evidence.
General: Humans carry 23 pairs of chromosomes in somatic cells, with one set of chromosomes inherited from each parent. Aneuploidy refers to cells that contain incorrect numbers of chromosomes. Trisomies occur when cells carry extra genetic material from a chromosome, either an entire chromosome (full trisomy) or a part of a chromosome (partial trisomy). Full trisomies occur randomly, and result from errors in cell division. Partial trisomies also occur randomly, and can result from translocations of genetic material from one chromosome to another. Mosaic trisomies occur when some (but not all) of the cells in the body contain extra chromosomes.
Full trisomy 13: Egg and sperm cells, also called gametes or germline cells, form in a process of cell division called meiosis. Normal gametes are haploid, or carry only one copy of each of the 23 chromosome pairs. One egg and one sperm unite to form a diploid zygote, which develops into an embryo. Full trisomy 13 occurs when meiotic non-disjunction results in gametes with two copies of chromosome 13, rather than one. Upon uniting with a complementary gamete, the resulting zygote has three copies of chromosome 13 rather than two.
Partial trisomy 13: In partial trisomy 13, only a portion of chromosome 13 is duplicated, and the partial duplication may be present in all cells or only in some cells. Partial trisomy 13 may occur if part of chromosome 13 translocates to another chromosome, and an extra portion of the chromosome is passed on through subsequent cell divisions. The symptoms associated with partial trisomies are often less severe than those of full trisomies.
Mosaic trisomy 13: Non-disjunction and translocation may also occur during somatic cell division (mitosis) in early development. As a result, some cells may have two copies of chromosome 13, while others may have an extra copy. Individuals who have cell populations with different genetic material are said to have mosaics. Thus, in mosaic trisomy 13, patients have three copies of a chromosome in some but not all cells. Mosaicism may also occur when two zygotes fuse to form one embryo. The symptoms of mosaic trisomy 13 are often less severe than full trisomy 13, although the clinical spectrum of the disease cannot be attributed entirely to different degrees of mosaicism.
Translocation trisomy 13: Chromosomal translocations result from rearrangements between different chromosomes. In balanced translocations, an even exchange of genetic material occurs, and carriers may have no apparent symptoms of trisomy 13. Unbalanced chromosomal translocations result in missing or extra genetic material. Both balanced and unbalanced translocations involving chromosome 13 may result in offspring with excess portions of the chromosome. Unlike trisomy 13 resulting from chromosomal non-disjunction, translocation trisomy 13 can be familial, or inherited.
SIGNS AND SYMPTOMS
General: The symptoms of trisomy 13 are generally severe, and affect many developmental processes and organ systems.
Developmental disorders: Developmental processes are severely affected in trisomy 13 patients, and may impede overall pre- and postnatal growth.
Development along the central portion (midline) of the embryo is often impaired, and may cause many of the facial defects found in trisomy 13, including cleft lip or palate in 70-80% of cases.
Eye defects are also common, occurring in 60-70% of cases. These defects include cyclopia (the presence of only one eye), microphthalmia (small eyes), or anophthalmia (no eyes).
Holoprosencephaly, a condition in which the two hemispheres of the brain are fused, is found in 60-70% of trisomy 13 patients. Holoprosencephaly is also associated with cleft lip/palate and other facial malformations.
Other common midline defects include single umbilical artery (13-28% of cases) and omphalocele, which is the protrusion of the abdominal organs through the navel (13% of cases).
Many of these developmental disorders may be visualized by prenatal sonography.
Neurological defects: Severe mental deficits are prevalent in trisomy 13, occurring in 100% of cases. Seizures are also common, occurring in 25-50% of trisomy 13 patients.
Cardiac and circulatory system: Cardiac (heart) defects affect 80-84% of patients with trisomy 13 and are a leading cause of neonatal death.
Extremities: Polydactyly (extra fingers and/or toes) are common in trisomy 13 patients, occurring in 60-70% of cases.
Other defects: Numerous other defects may be present in trisomy 13 patients. These include scalp defects (44%), kidney defects (37%), genital abnormalities (30%), abnormal levels of amniotic fluid (hydramnios, 25-40%), and excessive fluid in the brain (hydrocephaly, 5-7%).
Many malformations of trisomy 13 are apparent at birth. However, many features may also be detected prenatally by ultrasonography or ultrasound, including cleft lip/palate, holoprosencephaly, omphalocele, and single umbilical artery. Two-dimensional (2D) sonography may reveal more obvious defects, such as facial anomalies. However, 3-D (three-dimensional) sonography may allow more detailed analysis.
Cytogenetic studies are performed to examine a cell's chromosome spread or karyotype. These tests allow healthcare providers to detect extra chromosomes. Cytogenetic studies may be performed on chorionic villus samples or amniotic cells to diagnose trisomy 13 prenatally.
Because the features of trisomy 13 and Edwards' syndrome (trisomy 18) can be similar, cytogenetic testing is often necessary to accurately distinguish between these two conditions.
Computed tomography (CT) or magnetic resonance imaging (MRI) may reveal brain, heart, and other organ defects.
General: Trisomy 13 is characterized by various malformations that, although not unique to the disease, may result in multiple medical complications. The prognosis for patients with trisomy 13 is generally poor. The condition is associated with high rates of in-hospital deaths, and the majority of admitted patients die before discharge from the hospital.
Respiratory problems: Apnea, or the cessation of breathing, is one of the primary complications of trisomy 13. Many patients have respiratory problems, and breathe only with ventilator assistance. As a result, respiratory infections such as pneumonia are common. Cyanosis, or skin discoloration due to low oxygen saturation, is recurrent.
Heart defects: Heart problems frequently contribute to death in trisomy 13. Cardiac arrest (or the sudden failure of heart function) and heart disease are implicated in 69% and 13% of deaths, respectively.
Other complications: Trisomy 13 survivors are at increased risk for cancer and other malignancies.
General: The majority of trisomy 13 patients die soon after birth. However, 5-10% of them live beyond one year. In extremely rare cases, patients have survived well into their teens. Although life expectancy is difficult to predict for trisomy 13 patients, the associated defects are not always fatal and treatment may be available. Due to the multi-symptomatic nature of trisomy 13, treatment should be tailored to the specific problems displayed by each individual case.
Feeding assistance: Children with trisomy 13 require assistance with feeding, as difficulty with swallowing (dysphagia) is reported in a number of survivors. Parents may seek advice from dysphagia clinics in how to assist with feeding. Though some patients may be fed orally, others may be fed through tubes inserted through the nose, mouth, or abdomen. Patients fed through tubes may progress to oral feeding, and some children are fed both orally and through tubes.
Mental stimulation: Although serious mental and motor deficiencies are present in virtually all children with trisomy 13, it is suggested that increased stimulation and interaction may increase their limited developmental potential.
Surgery: Surgery may be able to correct or improve certain defects, such as cleft lip/palate and heart problems, depending on the severity. However, because post-surgical recovery is uncertain in trisomy 13 neonates, surgery is generally avoided in the months immediately following birth.
Other: Respiratory infections and pneumonia associated with chronic breathing problems should be treated accordingly.
Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of trisomy 13.
There is currently no known method for preventing trisomy 13. However, because of the possible risk of recurrence, parents with previous trisomy 13 pregnancies may undergo genetic testing to determine whether they are carriers of chromosome abnormalities. Individuals with a family history of trisomy 13 may also undergo genetic testing to determine whether they are carriers. Carriers may seek genetic counseling to determine their risks of passing on the translocations and giving rise to progeny with translocation trisomy 13.
Prenatal diagnostic tests may reveal whether a developing fetus has trisomy 13. Parents may seek counseling to better understand and cope with the medical complications of having a trisomy 13 newborn.
Parents of trisomy 13 children may also join support groups to develop strategies for coping with the difficulties associated with trisomy 13. Appropriate education and counseling should exist so parents can make informed decisions regarding the risks and benefits involved with potential prenatal intervention.
Parents who have previous trisomic births may also receive genetic counseling to determine the chances of having a child affected with trisomy 13.
Due to the prevalence of heart defects in trisomy 13 patients, echocardiograms should be performed to monitor heart function.
This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
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