NORD gratefully acknowledges Shashikant Kulkarni, PhD, Director of CytoGenomics and Molecular Pathology, Director of Clinical & Molecular Cytogenetics, Department of Pathology, Washington University School of Medicine, for assistance in the preparation of this report.
Chromosome 18, Tetrasomy 18p is a very rare chromosomal disorder in which the short arm of the 18th chromosome (18p) appears four times (tetrasomy) rather than twice in cells of the body. Individuals with a normal chromosomal make-up (karyotype) have two 18th chromosomes, both of which have a short arm ("18p") and a long arm ("18q"). However, in individuals with Chromosome 18, Tetrasomy 18p, four short arms (18ps) are present in cells of the body rather than the normal two.
The symptoms of Chromosome 18, Tetrasomy 18p may vary from case to case. Many affected individuals may have abnormalities of the head and facial (craniofacial) area; malformations of the spine, hands, and/or feet; neuromuscular abnormalities, such as increased muscle tone (hypertonia), increased reflex reactions (hyperreflexia), and difficulty coordinating movement; kidney (renal) malformations; and/or additional physical abnormalities. In addition, children and adults with Chromosome 18, Tetrasomy 18p often exhibit moderate to severe mental retardation, limitations in speech, and/or behavioral abnormalities. In most cases, Chromosome 18, Tetrasomy 18p is the result of a spontaneous (de novo) genetic change (mutation) early in embryonic development that occurs for unknown reasons (sporadic).
Chromosome 18, Tetrasomy 18p is a very rare chromosomal disorder in which the short arm of chromosome 18 (18p) appears four times (tetrasomy) rather than twice in cells of the body. Symptoms may vary from case to case.
Many infants with Chromosome 18, Tetrasomy 18p have a low birthweight, feeding problems, and a tendency to vomit. If necessary calories and nutrients are not obtained, affected infants may fail to thrive as a result.
Most infants with Chromosome 18, Tetrasomy 18p have abnormalities of the head and facial (craniofacial) area. The fibrous joint (sagittal suture) between the bones that form the sides of the skull (parietal bones) may close prematurely (dolichocephaly), causing the head to appear unusually long and narrow; the head may also be abnormally small (microcephaly), and the two sides of the face may appear to be of unequal shape and/or size (facial asymmetry). Affected infants may also have an abnormally small mouth; a highly arched roof of the mouth (palate); an unusually small jaw (micrognathia); malformed (dysplastic), low-set ears; and/or a pinched nose. In rare cases, additional craniofacial abnormalities may include vertical skin folds on either side of the nose (epicanthal folds) that may cover the eyes’ inner corners; eyes that are unusually close together (ocular hypotelorism); incomplete closure of the roof of the mouth (cleft palate); and/or overgrowth of the gums (gingival hypertrophy).
Individuals with Chromosome 18, Tetrasomy 18p often have several skeletal abnormalities. These may include a sideways curvative of the spine (scoliosis), sometimes occurring in association with a front-to-back curvative of the spine (kyphosis); an unusually small hipbone; and/or additional hip deformities (e.g., coxa valga). Many affected individuals exhibit malformations of the bones in the hands and/or feet, including fingers and/or toes that overlap and/or are unusually long, abnormally bent (clinodactyly), and/or webbed or fused (syndactyly). In some cases, the arches of the feet may also be flat (pes planus). Additional abnormalities of the hands may also be present, such as a single deep crease across the palms of the hands (simian crease) and/or absence of the horizontal ridges that are normally on the skin on the far end of the fingers (distal flexion ridges). Many affected individuals also tend to have a distinctive body shape, consisting of an abnormally thin build, narrow chest and shoulders, and unusually prominent bones and/or muscles (asthenic habitus).
In most people with Tetrasomy 18p, clusters of nerve fibers in the spinal cord (pyramidal tract) that help to regulate voluntary and reflex muscle activity may not function appropriately. As a result, affected individuals may exhibit several neuromuscular abnormalities, such as increased muscle tone (hypertonia); increased reflex reactions (hyperreflexia), including an abnormal reflex that consists of repeated flexing and relaxing of the foot (ankle clonus); and/or muscle stiffness and awkwardness in movement (spasticity). As affected people grow older, many may have an abnormal walking style (gait). In addition, in some individuals with Tetrasomy 18p, electrical disturbances may occur in the brain, causing involuntary tightening and relaxing (clonus) of specific muscles or muscle groups (motor seizures).
Many individuals with Chromosome 18, Tetrasomy 18p may also exhibit kidney (renal) abnormalities. For example, each kidney normally has a tube (ureter) that brings urine to the bladder. However, in some cases of Tetrasomy 18p, each kidney may have two such tubes (double ureter). If the double ureters fail to join together to become one tube before entering the bladder, one of the tubes may drain the urine in an inappropriate (ectopic) location. Blockage (obstruction) may result, causing an abnormal accumulation of urine in and swelling (distension) of the ureters (hydroureter) and kidneys (hydronephrosis). In addition, the other ureter may only be loosely embedded in the bladder, potentially causing backflow (reflux) of urine into the ureter, repeated bladder infections, and/or ureter blockage and hydronephrosis.
Other kidney abnormalities have also occurred in association with Chromosome 18, Tetrasomy 18p. For example, during normal development, the kidneys eventually “rotate” into their proper position in the back of the abdominal cavity. However, in some individuals with Tetrasomy 18p, the kidneys may not rotate into the appropriate position. As a result, the kidneys may be compressed by other organs that are also in the abdominal cavity, potentially causing abnormal renal function. In addition, in some cases of Tetrasomy 18p, the two kidneys may be united at the base, forming a horseshoe shape (horseshoe kidney); in such cases, kidney function is usually normal.
Some individuals with Tetrasomy 18p may have additional physical abnormalities. For example, at birth, some may have temporarily low levels of an antibody that helps fight infections (i.e., immunoglobulin A [IgA]). In addition, some individuals may exhibit a heart murmur and/or, in rare cases, failure of the testes to descend into the scrotum (cryptorchidism) in males.
In most cases, children and adults with Chromosome 18, Tetrasomy 18p also exhibit moderate to severe mental retardation, limited speech and vocabulary, and behavioral abnormalities.
Chromosome 18, Tetrasomy 18p is a rare chromosomal disorder in which the short arm of chromosome 18 (18p) appears four times (tetrasomy) rather than twice in cells of the body. 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.
Individuals with a normal chromosomal make-up (karyotype) have two 18th chromosomes, both of which consist of a short arm (18p), a long arm (18q), and a narrowed region at which the two arms are joined (centromere). However, people with Chromosome 18, Tetrasomy 18p have an extra chromosome known as an “isochromosome” that consists of two identical short arms (18ps) and a centromere. (An isochromosome is a chromosome with identical arms on each side of the centromere.) Therefore, a total of four short arms (18ps) are present in cells of the body rather than the normal two, resulting in the symptoms and physical findings that characterize this disorder.
In most affected individuals, Chromosome 18, Tetrasomy 18p has resulted from a spontaneous (de novo) change very early in embryonic development that occurred for unknown reasons (sporadically). In such cases, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.
However, there have been rare cases in which a parent also has an extra 18p isochromosome in all or some cells (i.e., chromosomal mosaicism). (Chromosomal mosaicism describes cases in which only a percentage of cells contains the chromosomal abnormality while other cells have a normal chromosomal makeup.) In such instances, it is believed that Chromosome 18, Tetrasomy 18p may have been inherited and that the chances are greater of having another child with the chromosomal abnormality. Chromosomal analysis and genetic counseling are recommended for parents of an affected child.
Chromosome 18, Tetrasomy 18p is a very rare chromosomal disorder that appears to affect males and females equally. Approximately 40 cases have been reported in the medical literature.
The diagnosis of Chromosome 18, Tetrasomy 18p may be determined before birth (prenatally) by specialized tests such as ultrasound, fetal blood sampling, amniocentesis, and/or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus. Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During fetal blood sampling, blood is drawn with a needle that is guided via ultrasound into the umbilical vein. With 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 analysis performed on fluid or tissue samples (i.e., obtained via fetal blood sampling, amniocentesis, or CVS) may reveal the presence of Chromosome 18p Tetrasomy.
The disorder may also be diagnosed and/or confirmed after birth (postnatally) by a thorough clinical evaluation, the detection of characteristic physical findings, and standard or specialized chromosomal studies (e.g., fluorescence in situ hybridization [FISH]). Additional diagnostic tests may also be conducted to help detect and/or characterize certain abnormalities that may be associated with the disorder.
The treatment of Chromosome 18, Tetrasomy 18p is directed toward the specific symptoms that are apparent in each individual. Such treatment may include surgical repair of craniofacial, skeletal, renal, and/or other malformations that may be associated with the disorder. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.
Other treatment of Chromosome 18, Tetrasomy 18p is symptomatic and supportive. A team approach may be helpful in ensuring that affected individuals reach their fullest potential. Such a team approach may include special remedial education, speech therapy, physical therapy, and other medical, social, or vocational services. Genetic counseling will also be of benefit for families of children with Chromosome 18, Tetrasomy 18p.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., mental retardation, craniofacial abnormalities, kidney defects, etc.].)
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