Chromosome 14, Trisomy Mosaic is a rare chromosomal disorder in which chromosome 14 appears three times (trisomy) rather than twice in some cells of the body. The term "mosaic" indicates that some cells contain the extra chromosome 14, whereas others have the normal chromosomal pair.
The disorder may be characterized by growth delays before birth (intrauterine growth retardation); failure to grow and gain weight at the expected rate (failure to thrive) during infancy; delays in the acquisition of skills requiring the coordination of mental and physical abilities (psychomotor delays); and mental retardation. Affected infants also have distinctive abnormalities of the head and facial (craniofacial) region, such as a prominent forehead; deeply set, widely spaced eyes; a broad nasal bridge; and low-set, malformed ears. Additional craniofacial abnormalities may include an unusually small lower jaw (micrognathia); a large mouth and thick lips; and incomplete closure or abnormally high arching of the roof of the mouth (palate). Many affected infants also have structural malformations of the heart (e.g., tetralogy of Fallot). In some cases, additional physical abnormalities may also be present.
The symptoms and physical findings associated with Chromosome 14, Trisomy Mosaic may depend on the percentage of cells containing the extra 14th chromosome. However, the syndrome is typically characterized by growth and developmental delays, mental retardation, distinctive craniofacial malformations, and/or other physical abnormalities.
Before birth, there may be excessive fluid in the amniotic sac (polyhydramnios), which is the thin-walled membrane surrounding the developing fetus during pregnancy. In addition, some infants with Chromosome 14, Trisomy Mosaic may be born prior to 37 weeks’ gestation (premature infant). (Gestation refers to the period of development from conception to birth. “Full-term” infants are born anywhere from 37 to 42 weeks of gestation.)
Chromosome 14, Trisomy Mosaic may also be characterized by abnormal growth delays before birth (prenatal growth retardation) and a failure to grow and gain weight at the expected rate (failure to thrive) during infancy. In addition, affected individuals typically have psychomotor delays and mental retardation.
The syndrome is also associated with characteristic craniofacial malformations, resulting in a distinctive appearance. Such features may include a prominent forehead; a broad nose; an unusually long vertical groove in the center of the upper lip (philtrum); a prominent upper jaw (maxilla); and a small, receding lower jaw (microretrognathia). Various eye (ocular) abnormalities may also be present, such as deeply set and/or widely spaced eyes (ocular hypertelorism); abnormal reduction in the size of the eyes (microphthalmia); narrow eyelid folds (palpebral fissures); mild drooping of the upper eyelids (ptosis); and/or a translucent film over the eyes. Affected infants may also have small, low-set, abnormally folded ears; a wide mouth and thick lips; incomplete closure (clefting) or unusually high arching of the roof of the mouth (palate); and/or a short, wide neck. In addition, in some cases, the face may appear relatively dissimilar from one side to the other (facial asymmetry).
Many infants with Chromosome 14, Trisomy Mosaic also have structural abnormalities of the heart that are present at birth (congenital heart defects), particularly tetralogy of Fallot. This congenital defect is characterized by a combination of distinctive heart (cardiac) malformations. These include an abnormal opening in the partition (septum) that separates the two lower chambers (ventricles) of the heart; obstruction of the proper outflow of blood from the lower right ventricle due to narrowing of the opening between the ventricle and the pulmonary artery (pulmonary stenosis); displacement of the aorta, enabling oxygen-depleted blood to flow from the right ventricle to the aorta; and thickening (hypertrophy) of the heart muscle (myocardium) of the right ventricle. (The pulmonary artery transports 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.) Associated symptoms and findings may include insufficient oxygen supply to body tissues (hypoxia), bluish discoloration of the skin and mucous membranes (cyanosis), shortness of breath (dyspnea), feeding difficulties, failure to thrive, and/or other abnormalities. In some instances, Chromosome 14, Trisomy Mosaic may be associated with other cardiac defects. In severe cases, congenital heart disease may lead to potentially life-threatening complications.
In some individuals with the syndrome, additional physical abnormalities may also be present. For example, according to reports in the medical literature, many infants with Chromosome 14, Trisomy Mosaic have had areas of abnormally increased skin pigmentation (hyperpigmentation) that may appear in a linear, spirallike (whorl), patchy, or netlike (reticular) distribution. Additional physical findings associated with the syndrome have included genital malformations in affected males, including undescended testes (cryptorchidism) and/or an abnormally small penis; body asymmetry, such as dissimilarity in the length of the arms or the legs (limb length asymmetry); and/or other skeletal abnormalities, such as dislocation of the hips, overlapping of certain fingers or toes, and/or other features.
In individuals with Chromosome 14, Trisomy Mosaic, chromosome 14 is present three times (trisomy) rather than twice in some cells of the body (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,” a long arm identified by the letter “q,” and a narrowed region at which the two arms are joined (centromere).
The same chromosomal (i.e., karyotypical) makeup is usually present in all body cells. (“Karyotype” refers to the full chromosome set within the nucleus of a cell.) However, those with a mosaicism have two or more cell lines that are karyotypically distinct. In individuals with Chromosome 14, Trisomy Mosaic, there is trisomy (duplication) of chromosome 14 in a percentage of cells, while other cells have a normal chromosomal makeup. The additional chromosome is responsible for the symptoms and physical findings that characterize the syndrome. Individuals with a low percentage of affected cells (low mosaicism) may have fewer, less severe symptoms than those with a high percentage of affected cells (high mosaicism).
Chromosome 14, Trisomy Mosaic appears to result from errors of chromosomal separation (nondisjunction) during the division of reproductive cells in one of the parents (parental meiosis) or during cellular division after fertilization (fetal mitosis). There have been some reports in which the syndrome has appeared to occur due to uniparental disomy or the formation of an isochromosome (14q isochromosome). Uniparental disomy is a chromosomal abnormality in which affected individuals have inherited both copies of a chromosomal pair from one parent, rather than one copy from each parent. An isochromosome is an abnormal chromosome with identical arms on each side of the centromere.
In observed cases, Chromosome 14, Trisomy Mosaic has appeared to affect females more frequently than males. Since the chromosomal syndrome was originally described in the medical literature, over 20 cases have been reported.
A diagnosis of Chromosome 14, Trisomy Mosaic may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus. Ultrasonography may reveal characteristic findings that suggest Chromosome 14, Trisomy Mosaic, such as excessive fluid in the membranous sac surrounding the developing fetus (polyhydramnios), growth retardation, and/or certain physical malformations (e.g., cleft palate). During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, whereas CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on the fluid or tissue samples may reveal the presence of Chromosome 14, Trisomy Mosaic.
The diagnosis may also be made or confirmed after birth (postnatally) based upon a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. In addition, specialized testing may also be conducted to detect or characterize certain abnormalities that may be associated with the disorder, such as congenital heart defects. Cardiac evaluation may include clinical examination with a stethoscope to evaluate heart and lung sounds; x-ray studies; tests that record the electrical activities of the heart muscle (electrocardiography [EKG]); a technique in which sound waves are directed toward the heart, enabling evaluation of cardiac motion and structure (echocardiogram); or other measures (e.g., cardiac catheterization).
The treatment of Chromosome 14, Trisomy Mosaic is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; physicians who diagnose and treat heart abnormalities (cardiologists); and/or other health care professionals.
If affected infants and children with tetralogy of Fallot have episodes in which cyanosis suddenly worsens (hypoxic spells), treatment may include the administration of oxygen, morphine, sodium bicarbonate, or other therapies as required to help improve oxygen concentration. In addition, in those with tetralogy of Fallot, surgical measures may be necessary to help alleviate symptoms and correct heart malformations (e.g., palliative systemic-to-pulmonary artery shunt, corrective open-heart surgery). Because individuals with tetralogy of Fallot may be susceptible to bacterial infection of the internal lining of the heart (endocarditis), antibiotics should be prescribed before and after dental visits and surgical procedures. Respiratory infections must also be treated vigorously and early.
In some infants and children with Chromosome 14, Trisomy Mosaic, treatment may also include the surgical repair of certain craniofacial, genital, or other abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors. Other treatment is symptomatic and supportive.
Early intervention may be important in ensuring that children with Chromosome 14, Trisomy Mosaic reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for affected individuals and their families.
Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of chromosomal disorders in the future.
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