Chromosome 18, Tetrasomy 18p

Chromosome 18, Tetrasomy 18p

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Chromosome 18, Tetrasomy 18p is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Tetrasomy, Short Arm of Chromosome 18

Disorder Subdivisions

  • None

General Discussion

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).

Symptoms

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.

Causes

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.

Affected Populations

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.

Standard Therapies

Diagnosis

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.



Treatment

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.

Investigational Therapies

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

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Behrman RE, et al., eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:283-84.



Wyngaarden JB, et al., eds. Cecil Textbook of Medicine. 19th ed. Philadelphia, PA: W.B. Saunders Company; 1992:613.



Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:385-86.



JOURNAL ARTICLES

Eggermann T, et al. Aberrations of chromosome 18 and their significance in genetic counseling. Orv Hetil. 2000;141:1667-71.



Habecker-Green JG, et al. Prenatal diagnosis and clinical features of an individual with tetrasomy 18p and trisomy 18q mosaicism. J Perinatol. 1998;18:395-98.



Eggermann T, et al. Tetrasomy 18p caused by paternal meiotic nondisjunction. Eur J Hum Genet. 1997;5:175-77.



Esmer MC, et al. Fluorescence in situ hybridization in 6 patients with alterations of chromosome 18 and in 7 with marker chromosomes. Rev Invest Clin. 1996;48:27-33.



Eggermann T, et al. Tetrasomy 18p de novo: identification by FISH with conventional and microdissection probes and analysis of parental origin and formation by short sequence repeat typing. Hum Genet. 1996;97:568-72.



Bugge M, et al. Tetrasomy 18p de novo: parental origin and different mechanisms of formation [published erratum appears in Eur J Hum Genet. 1996;4:291]. Eur J Hum Genet. 1996;4:160-67.



Esmer MC, et al. Tetrasomy 18p in two cases confirmation by in situ hybridization. Ann Genet. 1994;37:156-59.



Back E, et al. De novo isochromosome 18p in two patients: cytogenetic diagnosis and confirmation by chromosome painting. Clin Genet. 1994;45:301-04.



Abeliovich D, et al. Isochromosome 18p in a mother and her child. Am J Med Genet. 1993;46:392-93.



Mewar R, et al. Confirmation of isochromosome 18p using whole chromosome arm-specific fluorescence in situ hybridization. Cytogenet Cell Genet. 1993;64:1-4.



Park VM, et al. Diagnosis of tetrasomy 18p using in situ hybridization of a DNA probe to metaphase chromosomes. Am J Med Genet. 1991;41:180-83.



Callen DF, et al. The isochromosome 18p syndrome: confirmation of cytogenetic diagnosis in nine cases by in situ hybridization. Am J Hum Genet. 1990;47:493-98.



Singer TS, et al. Tetrasomy 18p in a child with trisomy 18 phenotype. Am J Med Genet. 1990;36:144-47.



Takeda K, et al. Sibs with tetrasomy 18p born to a mother with trisomy 18p. J Med Genet. 1989;26:195-97.



Rivera H, et al. Tetrasomy 18p: a distinctive syndrome. Ann Genet. 1984;27:187-89.

Resources

Children's Craniofacial Association

13140 Coit Road

Suite 517

Dallas, TX 75240

USA

Tel: (214)570-9099

Fax: (214)570-8811

Tel: (800)535-3643

Email: contactCCA@ccakids.com

Internet: http://www.ccakids.com



Support Organization for Trisomy 18, 13, and Related Disorders

2982 S. Union Street

Rochester, NY 14624-1926

Fax: (585)594-1957

Tel: (800)716-7638

Email: barbv@trisomy.org

Internet: http://www.trisomy.org



March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



AmeriFace

P.O. Box 751112

Limekiln, PA 19535

USA

Tel: (702)769-9264

Fax: (702)341-5351

Tel: (888)486-1209

Email: info@ameriface.org

Internet: http://www.ameriface.org



Chromosome Disorder Outreach, Inc.

P.O. Box 724

Boca Raton, FL 33429-0724

USA

Tel: (561)395-4252

Fax: (561)395-4252

Email: info@chromodisorder.org

Internet: http://www.chromodisorder.org/CDO/



National Kidney Foundation

30 East 33rd Street

New York, NY 10016

Tel: (212)889-2210

Fax: (212)689-9261

Tel: (800)622-9010

Email: info@kidney.org

Internet: http://www.kidney.org



Chromosome 18 Registry & Research Society

7155 Oakridge Drive

San Antonio, TX 78229

Tel: (210)657-4968

Fax: (210)657-4968

Email: office@chromosome18.org

Internet: http://www.chromosome18.org



NIH/National Kidney and Urologic Diseases Information Clearinghouse

3 Information Way

Bethesda, MD 20892-3580

Fax: (703)738-4929

Tel: (800)891-5390

TDD: (866)569-1162

Email: nkudic@info.niddk.nih.gov

Internet: http://www.kidney.niddk.nih.gov/



UNIQUE - Rare Chromosome Disorder Support Group

P.O. Box 2189

Caterham

Surrey, CR3 5GN

United Kingdom

Tel: 4401883330766

Fax: 4401883330766

Email: info@rarechromo.org

Internet: http://www.rarechromo.org



Craniofacial Foundation of America

975 East Third Street

Chattanooga, TN 37403

Tel: (423)778-9176

Fax: (423)778-8172

Tel: (800)418-3223

Email: terry.smyth@erlanger.org

Internet: http://www.craniofacialfoundation.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Tetrasomy 18p Canada

14 Deeth Drive, Unit A

Weston

Ontario, M9P 2J7

Canada

Tel: 4167687311

Tel: 6478009889

Email: Lorrine@tetrasomy18p.ca, Velvet@tetrasomy18p.ca

Internet: http://www.tetrasomy18p.ca



For a Complete Report

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