Last updated:
5/2/2024
Years published: 1995, 1996, 2001, 2024
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for assistance in the preparation of this report.
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 number 9 chromosomes, both of which have a short arm (“9p”) and a long arm (“9q”). In individuals with tetrasomy 9p, four short arms (9p) are present in cells rather than the normal two.
The symptoms of tetrasomy 9p may vary greatly in range and severity from person to person. Associated abnormalities may include mild growth delay, moderate to severe delay in the attainment of skills requiring the coordination of muscular and mental activities (psychomotor delay) and/or moderate to severe intellectual disability. In addition, the disorder may be characterized by various physical abnormalities such as malformations of the skull and facial differences, abnormalities of the hands and fingers, skeletal malformations and/or heart (cardiac) defects. Tetrasomy 9p appears to result from spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons (sporadically).
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 most patients, this chromosomal abnormality is present in all cells of the body; however, in some affected people, only some cells have tetrasomy 9p and other cells have a normal chromosomal make-up, and this is called mosaicism. Symptoms vary in affected individuals, depending upon whether mosaicism is present and, if so, what percentage of cells contain the tetrasomy 9p abnormality.
People with tetrasomy 9p may have a variety of physical and developmental abnormalities. Physical characteristics associated with the disorder may include abnormalities of the head and facial differences 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 differences may include vertical skin folds on either side of the nose that may cover the eyes’ inner corners (epicanthal folds) and/or unusually a small, receding jawbone (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 tetrasomy 9p also have abnormal 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).
Some people with 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). Rarely, affected individuals may have 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.
Most people with tetrasomy 9p also have developmental abnormalities, such as low birthweight, mild growth delay and/or moderate to severe delay in the attainment of skills requiring coordination of muscular and mental activity (psychomotor delay). Moderate to severe intellectual disability may also be present.
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 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 number 9 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 in the medical literature indicate that people with 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. An isochromosome is a mirror-image abnormal chromosome consisting of two copies of either a short arm or a long arm. When the isochromosome contains two centromeres or part of the long (q) arm, this is described as an isodicentric chromosome.
In most patients, 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 a mosaic pattern is present and, if so, what percentage of cells contain the tetrasomy 9p abnormality.
Most cases are due to the chromosomes 9 in one parent not separating in the process of forming the eggs or sperm (non-disjunction). This leads to an additional chromosome 9 that is then broken in the long arm and is followed by a duplication of the short arm containing the centromere (long arms are lost because they do not contain the centromere). 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.
Tetrasomy 9p is a very rare chromosomal disorder that appears to affect males slightly more often than females. Approximately 70 cases have been reported in the medical literature. About 30% of all known cases are mosaic.
In some cases, the diagnosis of tetrasomy 9p may be suggested. before birth 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 the fluid or tissue samples may show tetrasomy 9p. When tetrasomy 9p is not present in all of the cells (mosaicism), chromosomal studies of fluid or tissue samples may not show the tetrasomy.
The diagnosis of tetrasomy 9p may be confirmed after birth by a thorough clinical evaluation, characteristic physical 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).
Treatment
The treatment of 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.
Doctors may recommend surgery to correct or repair certain craniofacial, skeletal and/or other abnormalities associated with the disorder. In addition, for those with congenital heart defects, treatment with certain medications, surgery 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 is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
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Some current clinical trials also are posted on the following page on the NORD website:
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For information about clinical trials sponsored by private sources, contact:
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TEXTBOOKS
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.
JOURNAL ARTICLES
Papoulidis I, Kontodiou M, Tzimina M, et al. Tetrasomy 9p mosaicism associated with a normal phenotype in two cases. Cytogenet Genome Res. 2012;136(4):237-241. doi:10.1159/000337520
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.
INTERNET
Tetrasomy 9p. UNIQUE. Understanding Chromosome and Gene disorders. 2018. https://www.rarechromo.org/media/information/Chromosome%20%209/Tetrasomy%209p%20FTNW.pdf Accessed Feb 15, 2024.
Prevalence of Rare Diseases. Orphanet Report series. November 2023. https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Accessed Feb 15, 2024.
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