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Penta X Syndrome is a rare chromosomal disorder that affects females. Females normally have two X chromosomes. However, in those with Penta X Syndrome, there are three additional (or a total of five) X chromosomes in the nuclei of body cells (pentasomy X). The condition is typically characterized by moderate to severe mental retardation, short stature, malformations of the skull and facial (craniofacial) region, and/or other physical abnormalities. Characteristic craniofacial malformations may include upslanting eyelid folds (palpebral fissures), a flat nasal bridge, malformed ears, a short neck with a low hairline, and/or other findings. Penta X Syndrome may also be characterized by abnormal deviation (clinodactyly) or permanent flexion (camptodactyly) of the "pinkies" or fifth fingers; heart and/or kidney defects; deficient development of the ovaries and uterus; and/or other physical findings. The disorder results from errors during the division of reproductive cells in one of the parents.
Penta X Syndrome is characteristically associated with growth delays before birth (prenatal growth deficiency); failure to grow and gain weight at the expected rate (failure to thrive) after birth; and short stature. In addition, infants and children with Penta X Syndrome typically have delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation) and are affected by moderate to severe mental retardation.
The disorder is also characterized by distinctive malformations of the skull and facial (craniofacial) region. These often include an unusually small head (microcephaly); a round face; upslanting eyelid folds (palpebral fissures); a flat nasal bridge; low-set, malformed ears; and/or a short neck with a low hairline. Some affected individuals also have additional eye (ocular) abnormalities, such as widely spaced eyes (ocular hypertelorism); vertical skin folds that may cover the eyes' inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); and/or partial absence of tissue from the irides or the colored regions of the eyes (iris colobomas). Additional features reported in association with Penta X Syndrome have included abnormal, rudimentary outgrowths of tissue in front of the external ears (preauricular tags); a small jaw (micrognathia); thick lips; incomplete closure of the roof of the mouth (cleft palate); and/or other findings. In addition, dental abnormalities may be present, such as abnormal contact of the teeth of the upper jaw with those of the lower jaw (malocclusion); unusually shaped molars with large pulp spaces (taurodontism); and/or enamel defects, potentially resulting in premature loss of certain "baby" (deciduous or primary) teeth.
Females with Penta X Syndrome may also have various musculoskeletal defects, such as abnormal fusion of the forearm bones (radioulnar synostosis); narrow shoulders; and/or unusually small hands with abnormal deviation (clinodactyly) or permanent flexion (camptodactyly) of the fifth fingers. Additional findings may include overlapping toes; a foot deformity in which the sole is turned inward (metatarsus varus); and/or an abnormality in which the knees are unusually close together and the space between the ankles is increased ("knock knees" [genua valga]). Some affected females also have overflexion or bending (i.e., hyperflexion) or dislocations of multiple joints, including those of the fingers, wrists, shoulders, elbows, and/or hips. In addition, reports indicate that some affected individuals may have abnormal skin ridge patterns (dermatoglyphics) on the fingers and palms of the hands.
In some cases, Penta X Syndrome may be associated with certain structural malformations of the heart at birth (congenital heart defects). Such defects may include an abnormal opening in the fibrous partition (septum) that normally separates the two lower chambers of the heart (ventricular septal defect [VSD]); patent ductus arteriosus (PDA); and/or other malformations. In PDA, the channel that is present between the aorta and the pulmonary artery during fetal development fails to close after birth, leaving an abnormal opening between the arteries. (The pulmonary artery transports oxygen-depleted [deoxygenated] blood from the right ventricle to the lungs, where the exchange of oxygen and carbon dioxide takes place. The aorta is the main artery of the body that arises from the left ventricle and supplies oxygenated blood to body tissues.)
Some females with Penta X Syndrome also have certain kidney (renal) abnormalities, such as underdevelopment of the kidneys (renal hypoplasia), horseshoe kidney, and/or other findings. Horseshoe kidney is a congenital abnormality in which the two kidneys are joined at the base.
In some cases, affected females may also have an unusually small uterus, deficient development of the ovaries, and/or other abnormalities. In addition, delayed puberty has been reported in some instances.
Penta X Syndrome is a chromosomal disorder characterized by the presence of three extra X chromosomes. 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 that normally consists of an X and a Y chromosome for males and two X chromosomes for females. Therefore, females with a normal chromosomal make-up (karyotype) have 46 chromosomes, including two X chromosomes (46,XX karyotype); they receive one chromosome from the mother and one from the father in each of the 23 pairs.
However, females with Penta X Syndrome have 49 chromosomes, five of which are X chromosomes (49,XXXXX karyotype). The presence of the three additional X chromosomes results from errors during the division of reproductive cells in one of the parents (nondisjunction during meiosis). Evidence suggests that the extra X chromosomes are typically derived from the mother. In addition, researchers indicate that the risk of such errors may increase with advanced parental age.
Penta X Syndrome is a rare chromosomal disorder that affects only females. Since the syndrome was originally described in 1963 (Kesaree N), over 20 cases have been reported in the medical literature. Some females with Penta X Syndrome were originally thought to be affected by Down Syndrome due to the presence of certain features sometimes associated with the latter disorder. (For further information, please see the "Related Disorders" section of this report below.)
Certain symptoms of the following disorders may be similar to those of Penta X Syndrome. Comparisons may be useful for a differential diagnosis:
Down Syndrome, a disorder that affects both females and males, is considered the most common chromosomal syndrome. As noted above, some females with Penta X Syndrome were initially thought to have Down Syndrome due to detection of certain findings potentially seen in the latter, more common disorder. In females and males with Down Syndrome, all or a portion of chromosome 21 appears three times (trisomy) rather than twice in cells of the body. In some cases, only a percentage of cells may contain the chromosomal abnormality (mosaicism).
Symptoms and findings associated with Down Syndrome may be variable, depending on the specific location of the duplicated (trisomic) portion of chromosome 21; the percentage of cells containing the abnormality; and/or other factors. However, in many cases, the disorder is characterized by low muscle tone (hypotonia); a tendency to keep the mouth open with protrusion of the tongue; and distinctive craniofacial malformations, such as a short, small head (microbrachycephaly), upwardly slanting eyelid folds (palpebral fissures), a depressed nasal bridge, a small nose, and a relatively flat facial profile. Individuals with Down Syndrome may also have unusually small, misshapen (dysplastic) ears; a narrow roof of the mouth (palate); vertical skin folds that may cover the inner corners of the eyes (epicanthal folds); dental abnormalities; and excessive skin on the back of the neck. Limb abnormalities are also often present, such as unusually short arms and legs; excessive flexibility of the joints; improper development (dysplasia) of the middle bone (phalanx) of the fifth fingers; and unusual skin ridge patterns (dermatoglyphics) on the fingers, palms, and toes. Affected individuals may also have short stature; improper development of the pelvis; poor coordination; mild to severe mental retardation; hearing impairment; congenital heart defects; and/or additional symptoms and physical findings. In most cases, duplication of chromosome 21 appears to result from errors during the division of reproductive cells in one of the parents. (For further information, choose "Down" or "trisomy 21" as your search term in the Rare Disease Database.)
Triplo X Syndrome is a chromosomal abnormality in which females have an extra X chromosome (trisomy X) in the nuclei of body cells. No specific pattern of symptoms and malformations (phenotype) has been found to be associated with this abnormal chromosomal make-up (i.e., 47,XXX karyotype). Many affected females appear to have no or very few associated symptoms, while others may have various abnormalities. However, investigators indicate that Triplo X Syndrome is a relatively common cause of learning difficulties, particularly language-based disabilities (e.g., dyslexia), in females. Evidence suggests that females with Triplo X Syndrome typically have normal intelligence with IQs that tend to be lower than that of their brothers and sisters (siblings); mental retardation rarely occurs. Infants and children with Triplo X Syndrome may tend to have delayed acquisition of certain motor skills as well as delayed language and speech development.
Females with Triplo X Syndrome often are of tall stature. In addition, in some cases, certain physical abnormalities have been reported, such as a relatively small head; vertical skin folds that may cover the eyes' inner corners (epicanthal folds); abnormal development of the ovaries and/or the uterus; and/or other findings. Triplo X Syndrome results from errors during the division of reproductive cells in one of the parents. (For further information, please choose "Triplo X" as your search term in the Rare Disease Database.)
Tetra X Syndrome is a rare chromosomal abnormality in which females have two extra X chromosomes in the nuclei of body cells (48,XXXX karyotype). As with Triplo X Syndrome, no specific pattern of symptoms and malformations (phenotype) has been associated with this chromosomal abnormality. However, mild to moderate (or, more rarely, severe) mental retardation appears to be a consistent finding. Affected females also commonly have speech difficulties and behavioral abnormalities. In some cases, Tetra X Syndrome may also be associated with certain craniofacial abnormalities, such as widely set eyes (ocular hypertelorism), upslanting eyelid folds (palpebral fissures), vertical skin folds that may cover the eyes' inner corners (epicanthal folds), a relatively small jaw (micrognathia), and/or other findings. Other associated features may sometimes include abnormal deviation (clinodactyly) of the fifth fingers, fusion of the forearm bones (radioulnar synostosis), webbing of the neck, and/or other abnormalities. Affected females may also have incomplete development of secondary sexual characteristics, such as sparse pubic and underarm hair, small breasts, absence or irregularity of menstrual cycles, and, in some cases, underdevelopment of external genitalia. Tetra X Syndrome results from errors during the division of a parent's reproductive cells (nondisjunction during meiosis).
Turner Syndrome, a rare chromosomal disorder that affects females, is characterized by absence of all or a portion or impaired functioning of one of the X chromosomes (45,X karyotype). In some cases, some cells may have the normal pair of X chromosomes while other cells do not (45,X/46,XX mosaicism). In addition, evidence suggests that some affected individuals have Y chromosomal material in addition to the X chromosome in some or all cells. Females with Turner Syndrome may have a short, webbed neck with a low hairline; short stature; widely spaced, inverted, and/or underdeveloped (hypoplastic) nipples; heart defects; and/or kidney abnormalities. In addition, some affected females may have certain craniofacial abnormalities, such as a small jaw (micrognathia), a narrow roof of the mouth (palate), droopy upper eyelids (ptosis), widely spaced eyes (ocular hypertelorism), and/or other findings. In many cases, immature (streak) ovaries are present that cannot produce the female hormone estrogen. As a result, normal secondary sexual characteristics may fail to develop (e.g., the appearance of pubic hair, breast development, menstruation [primary amenorrhea]). Intellectual abilities are usually normal; however, some individuals may have problems with visual-spatial relations, poor coordination, and/or other abnormalities. Turner Syndrome is thought to result from errors during the division of a parent's reproductive cells. (For more information on this disorder, choose "Turner" as your search term in the Rare Disease Database.)
Penta X Syndrome is diagnosed based upon thorough clinical examination; detection of characteristic physical findings; and chromosomal analysis that confirms the presence of three extra X chromosomes in body cells. In some instances, the abnormality may be detected before birth (prenatally) based on chromosomal analysis following certain procedures, such as amniocentesis or chorionic villus sampling (CVS). 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.
The treatment of Penta X Syndrome 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 disorders of the skeleton, joints, muscles, and related tissues (orthopedists); heart specialists; and/or other health care professionals.
For some affected individuals, recommended treatment may include surgical correction of certain craniofacial, musculoskeletal, or other malformations 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.
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., craniofacial abnormalities, congenital heart defects, mental retardation].)
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Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1997:8-13, 78-80.
Behrman RE, et al., eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:317-18.
Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:33-40, 63-64.
Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:391-93, 399-400, 1717-19.
Linden MG, et al. Sex chromosome tetrasomy and pentasomy. Pediatrics. 1995;96:672-82.
Leal CA, et al. Parental origin of the extra chromosomes in polysomy X. Hum Genet. 1994;94:423-26.
Martini G, et al. On the parental origin of the X's in a prenatally diagnosed 49,XXXXX syndrome. Prenat Diagn. 1993;13:763-66.
Favetta S, et al. Pentasomy X: a clinical case report. Pediatr Med Chir. 1992;14:551-54.
Kassai R, et al. Penta X syndrome: a case report with review of the literature. Am J Med Genet. 1991;40:51-56.
Deng HX, et al. Parental origin and mechanism of formation of polysomy X: an XXXXX case and four XXXXY cases determined with RFLPs. Hum Genet. 1991;86:541-44.
Hassold T, et al. Analysis of non-disjunction in sex chromosome tetrasomy and pentasomy. Hum Genet. 1990;85:648-50.
Fragoso R, et al. 49,XXXXX syndrome. Ann Genet. 1982;25:145-48.
Funderburk SJ, et al. Pentasomy X: report of patient and studies of X-inactivation. Am J Med Genet. 1981;8:27-33.
Schroeter C, et al. A new case of pentasomy X. Helv Paediatr Acta. 1980;35:233-41.
Monheit A, et al. The penta-X syndrome. J Med Genet. 1980;17:392-96.
Archidiacono N, et al. X pentasomy: a case and review. Hum Genet. 1979;52:69-77.
Kesaree N, et al. A phenotypic female with 49 chromosomes, presumably XXXXX. A case report. J Pediatr. 1963;63:1099.
Report last updated: 2008/05/05 00:00:00 GMT+0