Trisomy 13 Syndrome is a rare chromosomal disorder in which all or a portion of chromosome 13 appears three times (trisomy) rather than twice in cells of the body. In some affected individuals, only a percentage of cells may contain the extra 13th chromosome (mosaicism), whereas other cells contain the normal chromosomal pair.
In individuals with Trisomy 13 Syndrome, the range and severity of associated symptoms and findings may depend on the specific location of the duplicated (trisomic) portion of chromosome 1, as well as the percentage of cells containing the abnormality. However, in many affected infants and children, such abnormalities may include developmental delays, profound mental retardation, unusually small eyes (microphthalmia), an abnormal groove in the upper lip (cleft lip), incomplete closure of the roof of the mouth (cleft palate), undescended testes (cryptorchidism) in affected males, and extra (supernumerary) fingers and toes (polydactyly). Additional malformations of the head and facial (craniofacial) area may also be present, such as a relatively small head (microcephaly) with a sloping forehead; a broad, flat nose; widely set eyes (ocular hypertelorism); vertical skin folds covering the eyes; inner corners (epicanthal folds); scalp defects; and malformed, low-set ears. Affected infants may also have incomplete development of certain regions of the brain (e.g., the forebrain); kidney (renal) malformations; and structural heart (cardiac) defects at birth (congenital). For example, characteristic heart defects may include an abnormal opening in the partition dividing the upper or lower chambers of the heart (atrial or ventricular septal defects) or persistence of the fetal opening between the two major arteries (aorta, pulmonary artery) emerging from the heart (patent ductus arteriosus). Many infants with Trisomy 13 Syndrome fail to grow and gain weight at the expected rate (failure to thrive) and have severe feeding difficulties, diminished muscle tone (hypotonia), and episodes in which there is temporary cessation of spontaneous berathing (apnea). Life-threatening complications may develop during infancy or early childhood.
Associated symptoms and findings may vary in range and severity from case to case. However, Trisomy 13 Syndrome is often characterized by craniofacial, neurologic, heart (cardiac), and/or other defects.
Affected infants typically are unusually small and have feeding difficulties. Various craniofacial malformations are frequently present, such as an abnormally small head (microcephaly) and a sloping forehead; unusual wideness of the soft spots (fontanelles) at the front and back of the skull; incomplete closure of the roof of the mouth (palate); a small jaw; scalp ulceration at the top of the head; and/or low-set, malformed ears. Other characteristics may include a short neck; loose skin folds over the back of the neck; and/or the presence of a benign lesion or birthmark consisting of abnormal clusters of blood vessels (capillary hemangiomas), most frequently on the center of the forehead.
In addition, eye (ocular) abnormalities may include unusually small eyes (microphthalmia); partial absence of ocular tissue from the iris (iris coloboma); abnormal development of the retina (retinal dysplasia); vertical skin folds over the inner corners of the eyes (epicanthal folds); and/or other ocular defects. In addition, the eyebrows may be sparse or absent.
Trisomy 13 Syndrome is also frequently characterized by variable degrees of holoprosencephaly, a condition in which the forebrain fails to divide properly during embryonic development. In those with Trisomy 13 Syndrome, holoprosencephaly may result in various associated, midline facial defects, including closely set eyes (hypotelorism); an abnormal groove in the middle and side of the upper lip (median and lateral cleft lip); abnormalities of the nose; and/or other features. Associated cyclopia has occurred infrequently, characterized by fusion of the eye cavities (orbits) into a single cavity containing one eye.
Affected infants may also have additional abnormalities of the central nervous system (i.e., brain and spinal cord). Holoprosencephaly may be associated with episodes characterized by temporary cessation of spontaneous breathing (apnea) or sudden uncontrolled electrical activity in the brain (seizures). Many infants are thought to be deaf, and profound mental retardation is usually present. In addition, in some cases, additional features may include abnormal tone of voluntary (skeletal) muscles; absence of the band of nerve fibers that joins the two hemispheres of the brain (agenesis of the corpus callosum); underdevelopment of the cerebellum (cerebellar hypoplasia); hydrocephalus; and/or myelomeningocele. Hydrocephalus is a condition in which obstructed flow or impaired absorption of cerebrospinal fluid (CSF) results in an abnormal accumulation of CSF in the skull, usually under increased pressure. CSF is the protective fluid that circulates through the cavities (ventricles) of the brain, the canal containing the spinal cord (spinal canal), and the space between layers of the protective membranes (meninges) surrounding the brain and spinal cord (i.e., subarachnoid space). Myelomeningocele is characterized by protrusion of a membranous sac containing a portion of the spinal cord, its meninges, and CSF through a defect in the spinal column.
About 80 percent of infants with Trisomy 13 Syndrome also have congenital heart defects, such as atrial or ventricular septal defects or patent ductus arteriosus (PDA). In infants with PDA, the channel that is present between the pulmonary artery and the aorta during fetal development fails to close after birth. (The pulmonary artery carries oxygen-depleted blood from the right ventricle to the lungs, where the exchange of oxygen and carbon dioxide occurs. The aorta, the major artery of the body, arises from the left ventricle and supplies oxygen-rich blood to most arteries.) In some cases, other defects may be present involving the pulmonary artery and aorta, certain heart valves, and/or heart chambers. In addition, the heart may be located in the right side of the chest, instead of its normal location in the left side of the chest (dextrocardia).
Kidney (renal) defects may also occur. These may include multiple cysts in the kidneys; abnormal union of the two kidneys at the base (horseshoe kidney); and/or swelling of the kidneys with urine due to blockage or narrowing of the ureters (hydronephrosis), which carry urine into the bladder. Abnormalities of the genitals are also associated with Trisomy 13 Syndrome, including undescended testes (cryptorchidism) and an abnormally formed scrotum in affected males and underdeveloped ovaries and malformed uterus (bicornuate uterus) in affected females.
Infants with Trisomy 13 Syndrome also frequently have certain abnormalities of the hands and feet. These may include more than the normal number of fingers and/or toes (polydactyly); abnormal bending (flexion) and possible overlapping of fingers; and unusually rounded (hyperconvex) nails. The heels of the feet may be abnormally prominent. In addition, Trisomy 13 Syndrome may be associated with abnormal skin ridge patterns (dermatoglyphics), including a single deep crease across the palms of the hands (simian crease).
In some cases, other abnormalities may also be present. Such features may include thin ribs, an underdeveloped pelvis, certain muscle abnormalities, hernias, abnormal development of the pancreas, and/or other anomalies.
In individuals with Trisomy 13 Syndrome, all or a relatively large region of chromosome 13 is present three times (trisomy) rather than twice in cells. In about five percent of cases, only a percentage of cells contains the extra 13th chromosome (mosaicism).
Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.
Trisomy (or “duplication”) of a particular region or regions of chromosome 13 is responsible for the symptoms and findings that characterize the disorder. The severity and range of symptoms may depend on the length and location of the duplicated portion of the chromosome. In addition, those with trisomy 13 mosaicism typically have less severe symptoms; however, in such cases, disease manifestations may be extremely variable, ranging from near normal to the full spectrum of malformations.
In most individuals with Trisomy 13 Syndrome, duplication of chromosome 13 is caused by spontaneous (de novo) errors during the division of reproductive cells in one of the parents (e.g., nondisjunction during meiosis). Evidence suggests that the risk of such errors may increase with advanced parental age. In cases in which only a percentage of cells contains the trisomy 13 abnormality (mosaicism), errors may also occur during cellular division after fertilization (mitosis).
In about 20 percent of affected individuals, trisomy 13 results from a translocation involving chromosome 13 and another chromosome. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. For most individuals with Trisomy 13 Syndrome, such translocations occur spontaneously for unknown reasons (de novo); less commonly, they are transmitted by a parent who is a carrier of a “balanced” translocation. (If a chromosomal rearrangement is balanced–i.e., consists of an altered but balanced set of chromosomes–it is usually harmless to the carrier. However, balanced translocations are sometimes associated with a higher risk of abnormal chromosomal development in the carrier’s offspring. Chromosomal testing may determine whether a parent has a balanced translocation.)
Investigators suggest that certain symptoms and findings associated with Trisomy 13 Syndrome may result from overexpression of developmentally important genes on chromosome 13. For example, the gene that regulates production of an enzyme known as esterase D (ESD) has been located on the long arm (q) of chromosome 13 (13q14.11). Elevated levels of esterase D have been found in the kidney tissues of some affected infants. Further investigations are required to learn more about the specific underlying causes of Trisomy 13 Syndrome and the potential role of esterase D.
Trisomy 13 Syndrome is sometimes called Patau Syndrome, after one of the researchers (Patau K) who identified the syndrome’s trisomic origin in 1960. The syndrome appears to affect females slightly more frequently than males and occurs in about one in 5,000 to 12,000 live births.
Evidence suggests that approximately one percent of all recognized miscarriages occur in association with Trisomy 13 Syndrome. In addition, as noted above, the frequency of Trisomy 13 increases with advancing age of the mother.
Investigators have also suggested a possible association between preeclampsia and Trisomy 13. Preeclampsia is an abnormal condition of pregnancy characterized by the rapid onset of high blood pressure (hypertension), abnormal amounts of protein in the urine (proteinuria), and/or excessive retention of fluids (edema). According to researchers, the number of cases of preeclampsia appears to be significantly higher in women who are carrying a fetus with Trisomy 13 Syndrome than would be otherwise expected in the general population. In addition, the incidence appears significantly higher than when compared with pregnancies complicated by certain other chromosomal abnormalities (e.g., trisomy 18, trisomy 21 [Down Syndrome]). Such researchers suggest the possibility that a gene or genes on fetal chromosome 13 may influence the development of preeclampsia.
In some instances, a diagnosis of Trisomy 13 Syndrome may be suggested before birth (prenatally) by specialized tests, such as fetal ultrasonography, amniocentesis, and/or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves create an image of the developing fetus, potentially revealing findings that may suggest a chromosomal disorder or other abnormalities. For example, ultrasound findings that may be suggestive of Trisomy 13 may include holoprosencephaly, polydactyly, and growth retardation.
During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal studies performed on such samples may reveal the presence of an extra chromosome 13.
The diagnosis of Trisomy 13 Syndrome may be made or confirmed after birth (postnatally) by a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. Testing may also reveal unusual persistence of embryonic and/or fetal hemoglobin in the blood of newborns and infants with Trisomy 13 Syndrome. (Hemoglobin is the oxygen-carrying component of red blood cells.)
For infants diagnosed with the syndrome, careful monitoring and various specialized tests may be conducted to ensure early detection and appropriate management of conditions potentially associated with Trisomy 13 Syndrome.
The treatment of Trisomy 13 Syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a multidisciplinary team of medical professionals.
In some cases, recommended treatment may include surgical correction of certain abnormalities associated with the disorder. The surgical procedures performed will depend upon the nature and severity of the anatomical abnormalities, their associated symptoms, and other factors.
A supportive team approach for children with this disorder may be of benefit and may include physical therapy, medical, and/or social services. Genetic counseling will also be of benefit for families of children with Trisomy 13 Syndrome. Other treatment for this disorder is symptomatic and supportive.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No: 264480; Last Update: 7/11/00.
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