Chromosome 9, Tetrasomy 9p is a very rare chromosomal disorder in which the short arm of the ninth chromosome (9p) appears four times (tetrasomy) rather than twice in all or some cells of the body. Individuals with a normal chromosomal make-up (karyotype) have two 9th chromosomes, both of which have a short arm ("9p") and a long arm ("9q"). However, in individuals with Chromosome 9, Tetrasomy 9p, four short arms (9ps) are present in cells rather than the normal two.
The symptoms of Chromosome 9, Tetrasomy 9p may vary greatly in range and severity from case to case. Associated abnormalities may include mild growth retardation, moderate to severe delay in the attainment of skills requiring the coordination of muscular and mental activities (psychomotor retardation), and/or moderate to severe mental retardation. In addition, the disorder may be characterized by various physical abnormalities, such as malformations of the skull and facial (craniofacial) region, abnormalities of the hands and fingers, skeletal malformations, and/or heart (cardiac) defects. Chromosome 9, Tetrasomy 9p appears to result from spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons (sporadically).
Chromosome 9, Tetrasomy 9p is a very rare chromosomal disorder in which the short arm of chromosome 9 (9p) appears four times (tetrasomy) rather than twice in cells of the body. In the majority of cases, this chromosomal abnormality (Tetrasomy 9p) is present in all cells of the body; however, in some cases, only some cells exhibit Tetrasomy 9p (mosaicism) while others cells have a normal chromosomal make-up. Symptoms vary in affected individuals, depending upon whether such a mosaic pattern is present and, if so, what percentage of cells contain the Tetrasomy 9p abnormality.
People with Chromosome 9, Tetrasomy 9p may exhibit a variety of physical and developmental abnormalities. Physical characteristics associated with the disorder may include abnormalities of the head and facial (craniofacial) area, such as an unusually small head (microcephaly), abnormally wide spaces between fibrous joints (sutures) and bones in the skull (fontanelles), widely spaced eyes (ocular hypertelorism), and/or an abnormally rounded (bulbous) or beaked nose. Other facial abnormalities may include vertical skin folds on either side of the nose that may cover the eyes’ inner corners (epicanthal folds) and/or unusually small, receding jaw bones (microretrognathia). Affected individuals may also have a short neck; low-set, misshapen (dysplastic) ears; and/or various malformations of the hands and fingers, such as improperly developed (dysplastic) fingernails; fifth fingers that are abnormally bent (clinodactyly) and short (brachymesophalangy); and a single, deep crease across the palms of the hands (simian crease).
Most people with Chromosome 9, Tetrasomy 9p also exhibit improper skeletal development (dysplasia). As a result, their symptoms may include abnormally reduced bone mass (osteopenia); incomplete closure of bones in the spinal column surrounding the spinal cord (spina bifida occulta); and/or a sideways and front-to-back curvature of the spine (kyphoscoliosis). Other features may include abnormally prominent ribs (angulated costal arches) and/or delayed development (ossification) of the pelvic bone, the hip bones, and/or the shaft of the thigh bones (femoral heads). (For more information on spina bifida occulta, choose “Spina Bifida” as your search term in the Rare Disease Database.)
In some cases, people with Chromosome 9, Tetrasomy 9p may have additional physical abnormalities, including heart (cardiac) malformations and/or abnormalities of the eyes, such as sinking in of the eyeballs (enophthalmos) and/or crossing of the eyes (strabismus). Cerebral spaces in the brain (ventricles) may be abnormally widened (dilated), inhibiting the normal flow of cerebrospinal fluid; as a result, the fluid may accumulate in the skull and put pressure on brain tissue (hydrocephalus). In rare cases, affected individuals may display incomplete closure of the lip and the roof of the mouth (cleft lip and palate); kidney (renal) abnormalities; and/or failure of one or both testes to descend into the scrotum (cryptorchidism) in affected males. (For more information on these disorders, choose “Hydrocephalus” and “Cleft Palate” as your search terms in the Rare Disease Database.)
In almost all cases, individuals with Chromosome 9, Tetrasomy 9p also exhibit developmental abnormalities, such as low birthweight, mild growth retardation, and/or moderate to severe delay in the attainment of skills requiring coordination of muscular and mental activity (psychomotor retardation). Moderate to severe mental retardation may also be present.
Chromosome 9, Tetrasomy 9p is a very rare chromosomal disorder in which the short arm of chromosome 9 (9p) appears four times (tetrasomy) rather than twice in some or all of the cells of the body. When only some cells are affected, this is termed “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”.
Individuals with a normal chromosomal make-up (karyotype) have two 9th chromosomes, both of which consist of a short arm (9p), a long arm (9q), and a narrowed region at which the two arms are joined (centromere). However, reports indicate that people with Chromosome 9, Tetrasomy 9p typically have an extra chromosome that consists of two short arms (9ps). This abnormal chromosome may have one (isochromosome) or two centromeres (isodicentric). Therefore, in affected individuals, a total of four short arms (9ps) are present in cells of the body rather than the normal two, resulting in the symptoms that characterize this disorder.
In the majority of cases, the Tetrasomy 9p abnormality is present in all cells of the body; however, in some cases, only some cells may exhibit Tetrasomy 9p (mosaicism) while other cells contain a normal chromosomal make- up. Symptoms vary in affected individuals, depending upon whether such a mosaic pattern is present and, if so, what percentage of cells contain the Tetrasomy 9p abnormality.
Chromosome 9, Tetrasomy 9p appears to result from spontaneous (de novo) errors very early in embryonic development that occur 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.
Chromosome 9, Tetrasomy 9p is a very rare chromosomal disorder that appears to affect males slightly more often than females. Approximately 30 cases have been reported in the medical literature.
In some cases, the diagnosis of Chromosome 9, Tetrasomy 9p may be suggeste. before birth (prenatally) by specialized tests such as ultrasound. amniocentesis, and/or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves create an image of the developing fetus, potentially revealing certain findings that suggest a chromosomal disorder or other abnormalities. 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 studies performed on such fluid or tissue samples may reveal the presence of Tetrasomy 9p. In some cases. however, such as when Tetrasomy 9p is not present in all of the fetus' cell. (mosaicism), chromosomal studies of fluid or tissue samples may not revea. the tetrasomy.
The diagnosis of Chromosome 9, Tetrasomy 9p may be confirmed after birt. (postnatally) by a thorough clinical evaluation; detection of characteristic physica. findings; chromosomal studies; and other specialized tests. For example, in some cases, analysis may be performed to detect elevated activity of the galactose-1-phosphate uridyltransferase (GALT) enzyme, which is known to be regulated by a gene located on the short arm of chromosome 9 (9p13).
The treatment of Chromosome 9, Tetrasomy 9p 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 specialize in disorders of the skeleton, muscles, joints, and related tissues (orthopedists); heart specialists (cardiologists); eye specialists; physical therapists; and/or other health care professionals.
For some affected individuals, physicians may recommend surgical correction or repair of certain craniofacial, skeletal, and/or other abnormalities associated with the disorder. In addition, for those with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be necessary. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.
Early intervention may be important in ensuring that affected children 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. Other treatment for this disorder is symptomatic and supportive.
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Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:50, 82.
Buyse ML. Birth Defects Encyclopedia. Dover, Mass: Blackwell Scientific Publications, Inc; 1990:354-56.
Eggermann T, et al. New case of mosaic tetrasomy 9p with additional neurometabolic findings. Am J Med Genet. 1998;75:530-33.
Tonk VS. Moving towards a syndrome: a review of 20 cases and a new case of non-mosaic tetrasomy 9p with long-term survival. Clin Genet. 1997;52:23-29.
Andou R, et al. A case of tetrasomy 9p. Acta Paediatr Jpn. 1994;36:724-26.
Van Hove J, et al. Tetrasomy 9p: prenatal diagnosis and fetopathological findings in a second trimester male fetus. Ann Genet. 1994;37:139-42.
Grass FS, et al. Tetrasomy 9p tissue-limited idic(9p) in a child with mild manifestations and a normal CVS result. Report and review. Am J Med Genet. 1993;47:812-16.
Schaefer GB, et al. Tetrasomy of the short arm of chromosome 9: prenatal diagnosis and further delineation of the phenotype. Am J Med Genet. 1991;38:612-15.
Jalal SM, et al. Tetrasomy 9p: an emerging syndrome. Clin Genet. 1991;39:60-64.
Papenhausen P, et al. Tissue limited mosaicism in a patient with tetrasomy 9p. Am J Med Genet. 1990;37:388-91.
Balestrazzi P, et al. Tetrasomy 9p confirmed by GALT. J Med Genet. 1983;20:396-99.
Garcia-Cruz D, et al. Tetrasomy 9p: clinical aspects and enzymatic gene dosage expression. Ann Genet. 1982;25:237-42.
Eydoux P, et al. Gene dose effect for GALT in 9p trisomy and in 9p tetrasomy with an improved technique for GALT determination. Hum Genet. 1981;57:142-44.
Moedjono SJ, et al. Tetrasomy 9p: confirmation by enzyme analysis. J Med Genet. 1980;17:227-30.
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Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 230400; 3/12/01. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?230400.
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