|55 Kenosia Avenue
Danbury, CT 06810
Toll Free: 1.800.999.6673
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
Copyright 1994, 2000, 2003
Chromosome 22, Trisomy Mosaic is a rare chromosomal disorder in which chromosome 22 appears three times (trisomy) rather than twice in some cells of the body. The term "mosaic" indicates that some cells contain the extra chromosome 22, whereas others have the normal chromosomal pair.
The range and severity of associated symptoms and findings may vary, depending upon the percentage of cells with the chromosomal abnormality. However, characteristic features typically include growth delays, mental retardation, unequal development of the two sides of the body (hemidystrophy), and webbing of the neck. Affected individuals may also have abnormal outward deviation of the elbows upon extension (cubitus valgus), multiple pigmented moles or birthmarks (nevi), distinctive malformations of the head and facial (craniofacial) area, and other physical abnormalities.
The symptoms and physical findings associated with Chromosome 22, Trisomy Mosaic may depend on the percentage of cells containing the extra 22nd chromosome. However, the disorder is often characterized by mental retardation, severe growth and developmental delays, and other physical abnormalities.
In many individuals with the disorder, there is unequal development of the two sides of the body (hemidystrophy), causing the body to appear dissimilar from one side to the other. For example, one leg may appear shorter than the other. In addition, in many individuals with hemidystrophy, there is associated hearing loss affecting one ear (unilateral hearing impairment).
According to reports in the medical literature, individuals with Chromosome 22, Trisomy Mosaic typically have additional symptoms and findings that are also often seen in Turner syndrome, another chromosomal disorder. (For further information on Turner syndrome, please see the "Related Disorders" section of this report below.) Such abnormalities include short stature; abnormal outward deviation of the elbows upon extension (cubitus valgus); multiple pigmented birthmarks (nevi); and malformations of the heart and its major blood vessels (cardiovascular defects), particularly defects affecting the major artery (aorta) that carries oxygen-rich blood from the lower left chamber (ventricle) of the heart throughout the body. Chromosome 22, Trisomy Mosaic is also associated with additional malformations seen in Turner syndrome, such as drooping of the upper eyelids (ptosis); webbing of the neck; a low hairline at the back of the neck; malformed (dysplastic) nails; and defective development of the ovaries (ovarian dysgenesis) in affected females. The ovaries are the paired glands that produce female reproductive cells (eggs) and certain female hormones. Therefore, ovarian dysgenesis may be associated with delayed or failed development of secondary sexual characteristics during puberty (e.g., breast development, the appearance of pubic hair, menstruation) and infertility.
Some individuals with Chromosome 22, Trisomy Mosaic also have additional malformations of the head and facial (craniofacial) area. In addition to drooping of the upper eyelids (ptosis), such malformations may include widely spaced eyes (ocular hypertelorism); vertical skin folds covering the eyes' inner corners (epicanthal folds); and abnormal pits or indentations in front of the ears (preauricular pits). Some affected individuals have additional physical abnormalities, such as underdeveloped fingers and toes (digits); abnormal skin creases on the palms of the hands; and kidney (renal) malformations.
In individuals with Chromosome 22, Trisomy Mosaic, chromosome 22 is present three times (trisomy) rather than twice in some 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".
The same chromosomal (karyotypical) makeup is usually present in all body cells (i.e., one cell line). However, those with a chromosomal mosaicism have two or more cell lines. Chromosome 22, Trisomy Mosaic is characterized by an extra chromosome 22 in one of an individual's cell lines, with at least one unaffected cell line also present. The presence of the additional chromosome is responsible for the symptoms and physical findings that characterize the disorder. Individuals with a low percentage of affected cells may have fewer, less severe symptoms than those with a high percentage of affected cells.
In most individuals with Chromosome 22, Trisomy Mosaic, the disorder appears to result from errors (e.g., nondisjunction) during the division of reproductive cells in one of the parents (parental meiosis) or during cellular division after fertilization (fetal mitosis). There have also been reports in which the disorder has occurred in association with uniparental disomy, an abnormality in which affected individuals have inherited both copies of a chromosomal pair from one parent, rather than one copy from each parent.
Chromosome 22, Trisomy Mosaic appears to affect females more frequently than males. Approximately 15 cases have been reported in the medical literature.
Symptoms of the following disorders may be similar to those of Chromosome 22, Trisomy Mosaic. Comparisons may be useful for a differential diagnosis:
Chromosome 22, Trisomy 22 is a rare chromosomal disorder in which all or a portion of chromosome 22 appears to be present three times (trisomy) rather than twice in all cells of the body ("complete" or "non-mosaic" trisomy 22). (Researchers suggest that, in many cases, the extra chromosomal material is in fact a portion of chromosome 11.) Associated symptoms and findings may be variable. However, many affected individuals have developmental delays, mental retardation, and/or distinctive craniofacial abnormalities, such as an unusually small head (microcephaly), widely spaced eyes (ocular hypertelorism), vertical skin folds covering the eyes' inner corners (epicanthal folds), and incomplete closure of the roof of the mouth (cleft palate). Additional craniofacial defects may include an abnormally small jaw (micrognathia); absence or underdevelopment of the outer ears, with narrow, blind ending, or absent external ear canals; and/or the presence of abnormal pits or indentations in front of the ears (preauricular pits). In other cases, affected individuals have unusually large, low-set outer ears; an abnormally prominent forehead; a bulbous nose with a flat nasal tip; and/or an unusually long vertical groove (philtrum) between the nose and the upper lip. Individuals with Chromosome 22, Trisomy 22 may also have additional physical abnormalities, such as a short, webbed neck; underdeveloped bones at the ends of the fingers and toes (distal phalanges); congenital heart defects; and kidney (renal) defects. In some cases, neuromuscular and neurologic abnormalities may be present, including unusually low muscle tone (hypotonia) and episodes of uncontrolled electrical activity in the brain (seizures).
Turner syndrome is a rare chromosomal disorder that affects females. Normally, females have two X chromosomes (whereas males have one X and one Y chromosome) in body cells. However, in most females with Turner syndrome, one X chromosome is missing from the cells (45,X karyotype); in such cases, researchers suggest that approximately 40 percent of affected females may have some Y chromosomal material in addition to the one X chromosome. In other females with Turner syndrome, both X chromosomes may be present, but one may have genetic defects. In still other cases, some cells may have the normal pair of X chromosomes whereas other cells do not (45,X/46,XX mosaicism). Turner syndrome is often characterized by short stature; a short, webbed neck; a low hairline; drooping of the upper eyelids (ptosis); widely spaced eyes (ocular hypertelorism); and hearing impairment. Additional features may include widely spaced, inverted, and/or underdeveloped (hypoplastic) nipples; multiple pigmented birthmarks (nevi); abnormal outward deviation of the elbows upon extension (cubitus valgus); malformed nails; cardiac and aortic defects; and/or kidney (renal) abnormalities. In addition, in almost all cases, there is defective development of the ovaries (ovarian dysgenesis, e.g., immature [streak] ovaries). As a result, normal secondary sexual characteristics fail to develop during puberty, such as the appearance of pubic hair, breast development, and menstruation (primary amenorrhea). Almost all affected females are infertile. Although intellectual abilities are usually normal, some individuals may experience difficulties with visual-spatial relationships (e.g., right-left disorientation). Although the exact cause of Turner syndrome is not known, the disorder is thought to result from an error during the division (meiosis) of a parent's reproductive cells. (For more information on Turner syndrome, please choose "Turner" as your search term in the Rare Disease Database.)
Other chromosomal disorders may be characterized by symptoms and findings similar to those potentially associated with Chromosome 22, Trisomy Mosaic. Chromosomal testing is necessary to confirm the specific chromosomal abnormality present. (For further information on such chromosomal disorders, choose the name of the specific disorder in question or use "chromosome" as your search term in the Rare Disease Database.)
Noonan syndrome is a rare genetic disorder characterized by abnormalities of the head and facial (craniofacial) area; webbing of the neck; short stature; and/or distinctive malformations of the chest. For example, there may be abnormal prominence of the upper portion and/or depression of the lower portion of the breastbone (pectus carinatum and/or pectus excavatum). Additional abnormalities may also be present, such as heart defects; failure of one or both testes to descend into the scrotum (unilateral or bilateral cryptorchidism) in affected males; pigmented birthmarks (nevi), small black or dark brown "freckle-like" spots (lentigines), and/or larger, light brown discolorations ("cafe-au-lait" spots) on the skin; and mental retardation. Characteristic craniofacial abnormalities may include a triangular-shaped face, widely spaced eyes (ocular hypertelorism), drooping of the upper eyelids (ptosis), a highly arched roof of the mouth (palate), low-set ears, and/or other malformations. Noonan syndrome may be inherited as an autosomal dominant trait. In cases without a positive family history, the disorder appears to occur randomly due to new genetic mutations. (For more information on this disorder, choose "Noonan" as your search term in the Rare Disease Database.)
A diagnosis of Chromosome 22, Trisomy Mosaic may be suggested before birth (prenatally) by specialized tests, such as ultrasound, amniocentesis, or chorionic villus sampling (CVS). Fetal ultrasonography is a noninvasive diagnostic procedure during which reflected sound waves are used to create an image of the developing fetus. During amniocentesis, a sample of fluid that surrounds the 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 22, Trisomy Mosaic.
Other testing may also sometimes be conducted to help confirm the diagnosis. For example, according to reports in the medical literature, fetal skin biopsy may be recommended in some cases in which mosaicism has been detected during amniocentesis. Fetal skin biopsy involves the removal and microscopic examination of certain cells (e.g., fibroblasts) from the developing fetus.
A diagnosis of Chromosome 22, Trisomy Mosaic 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 be conducted to detect or characterize certain abnormalities that may be associated with the disorder (e.g., hearing impairment, cardiovascular defects, renal abnormalities, ovarian dysgenesis, etc.).
The treatment of Chromosome 22, 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); hearing specialists; and/or other health care professionals.
In some infants and children with Chromosome 22, Trisomy Mosaic, treatment may include the surgical repair of certain craniofacial, cardiovascular, 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. In addition, for some individuals with unilateral hearing loss, the use of artificial devices (prostheses) may be recommended, such as specialized hearing aids. Other treatment for the disorder is symptomatic and supportive.
Early intervention may be important in ensuring that children with Chromosome 22, Trisomy Mosaic reach their potential. Special services that may be beneficial include special education, speech therapy, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for affected individuals and their families.
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:
7272 Greenville Avenue
Dallas, TX 75231
Phone #: 214-784-7212
800 #: 800-242-8721
Home page: http://www.heart.org
PO Box 8126
Gaithersburg, MD 20898-8126
Phone #: 301-251-4925
800 #: 888-205-2311
Home page: http://rarediseases.info.nih.gov/GARD/
1275 Mamaroneck Avenue
White Plains, NY 10605
Phone #: 914-997-4488
800 #: 888-663-4637
Home page: http://www.marchofdimes.com
c/o Christine Rose
48 Froggatts Ride
West Midlands, B76 2TQ SOFT United Kingdom
Phone #: 012-135-13122
800 #: --
Home page: http://www.soft.org.uk
2982 S. Union Street
Rochester, NY 14624-1926
Phone #: N/A
800 #: 800-716-7638
Home page: http://www.trisomy.org
1825 K Street NW, Suite 1200
Washington, DC 20006
Phone #: 202-534-3700
800 #: 800-433-5255
Home page: http://www.thearc.org
P.O. Box 2189
Surrey, CR3 5GN United Kingdom
Phone #: 440-188-3330766
800 #: --
Home page: http://www.rarechromo.org
Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:395, 1717-1719.
Berghella V, et al. Prenatal confirmation of true fetal trisomy 22 mosaicism by fetal skin biopsy following normal fetal blood sampling. Prenat Diagn. 1998;18:384-389.
Crowe CA, et al. Mosaic trisomy 22: a case presentation and literature review of trisomy 22 phenotypes. Am J Med Genet. 1997;71:406-413. Comment in: Am J Med Genet. 1998;76:447.
Hirschhorn K. Mosaic trisomy 22: a case presentation and literature review of trisomy 22 phenotypes [letter]. Am J Med Genet. 1998;76:447. Comment on: Am J Med Genet. 1997;71:406-413.
Stoll C, et al. De novo trisomy 22 due to an extra 22Q-chromosome. Ann Genet. 1997;40:217-221.
de Pater JM, et al. Maternal uniparental disomy for chromosome 22 in a child with generalized mosaicism for trisomy 22. Prenat Diagn. 1997;17:81-86.
Phillips OP, et al. Risk of fetal mosaicism when placental mosaicism is diagnosed by chorionic villus sampling. Am J Obstet Gynecol. 1996;174:850-855.
Bacino CA, et al. Clinical and molecular studies in full trisomy 22: further delineation of the phenotype and review of the literature. Am J Med Genet. 1995;56:359-365. Comment in: Am J Med Genet. 1996;62:98-99, 100-101.
Robinson WP, et al. Mosaicism most likely accounts for extended survival of trisomy 22 [letter]. Am J Med Genet. 1996;62:100-101. Comment on: Am J Med Genet. 1995;56:359-365.
Woods CG, et al. Asymmetry and skin pigmentary anomalies in chromosome mosaicism. J Med Genet. 1994;31:694-701.
Lund HT, et al. Trisomy 22 mosaicism limited to skin fibroblasts in a mentally retarded, dysmorphic girl. Acta Paediatr Scand. 1990;79:714-718.
Lessick ML, et al. Trisomy 22 mosaicism with normal blood chromosomes. Case report with literature review. Clin Pediatr. 1988;27:451-454.
Wertelecki W, et al. Trisomy 22 mosaicism syndrome and Ullrich-Turner stigmata. Am J Med Genet. 1986;23:739-749.
Schinzel A, et al. Incomplete trisomy 22. III. Mosaic trisomy 22 and the problem of full trisomy 22. Hum Genet. 1981;56:269-273.
Dulitzky F, et al. Unilateral radial aplasia and trisomy 22 mosaicism. J Med Genet. 1981;18:473-476.
A. Schinzel, et al.;Incomplete trisomy 22. III .Mosaic trisomy 22 and the problem of full trisomy 22. Hum Genet 1981; 56(3):269-273.
Unilateral radial aplasia and trisomy 22 mosaicism.. F. Dulitzky,et al.; J Med Genet (Dec 1981; 18(6)). Pp. 473-476.
Shokeir MH. Complete trisomy 22. Clin Genet. 1978;14:139-146.
Report last updated: 2008/05/31 00:00:00 GMT+0