Chromosome 8, Monosomy 8p

Chromosome 8, Monosomy 8p

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Chromosome 8, Monosomy 8p 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

  • 8p- Syndrome, Partial
  • Chromosome 8, 8p Deletion Syndrome, Partial
  • Chromosome 8, Partial Deletion of Short Arm
  • Del(8p) Syndrome, Partial
  • Distal 8p Monosomy
  • Partial 8p Monosomy
  • Terminal 8p- Syndrome (8p21 to 8p23-pter), Included
  • Chromosome 8, Partial Monosomy 8p

Disorder Subdivisions

  • None

General Discussion

Chromosome 8, Monosomy 8p is a rare chromosomal disorder characterized by deletion (monosomy) of a portion of the eighth chromosome. Associated symptoms and findings may vary greatly in range and severity from case to case. However, common features include growth deficiency; mental retardation; malformations of the skull and facial (craniofacial) region, such as a small head (microcephaly) and vertical skin folds that may cover the eyes' inner corners (epicanthal folds); heart (cardiac) abnormalities; and/or genital defects in affected males. Additional craniofacial features may also be present that tend to become less apparent with age, such as a short, broad nose; a low, wide nasal bridge; and/or a small jaw (micrognathia). In most cases, Chromosome 8, Monosomy 8p appears to result from spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons.

Symptoms

As noted above, associated features may be extremely variable. However, in many cases, there are growth delays during fetal development (intrauterine growth retardation) as well as after birth (postnatal growth retardation).



The syndrome is also commonly associated with mild mental retardation, although more severe retardation may be seen in some instances. In addition, other cases have been described in which affected individuals have normal intelligence. Monosomy 8p may also be characterized by delays in the acquisition of skills that require the coordination of mental and motor activities (psychomotor retardation). According to reports in the medical literature, many affected children may have speech difficulties. In addition, behavioral problems are commonly seen during childhood, such as abnormally active (hyperactive), impulsive behavior and/or outbursts of aggressiveness.



Monosomy 8p is also typically characterized by craniofacial malformations that may be relatively subtle in some cases. In addition, a few cases have been reported in which such malformations are not apparent. Craniofacial features commonly seen with the syndrome include an unusually small head (microcephaly); a narrow skull and high forehead; low-set and/or malformed ears; and/or vertical skin folds that may cover the eyes' inner corners (epicanthal folds). As noted above, additional craniofacial abnormalities may also be present that may become less evident with age. Such features may include a flat, wide nasal bridge; a broad, short nose; a small, receding jaw (microretrognathia); and/or other abnormalities.



In addition, many affected individuals may have an unusually short neck; a broad chest; and/or widely set, underdeveloped (hypoplastic) nipples. Males with the syndrome may also have genital abnormalities, such as a developmental defect in which the testes have failed to descend into the pouchlike structure known as the scrotum (cryptorchidism); deficient activity of the testes (hypogonadism); and/or abnormal placement of the urinary opening (hypospadias), such as on the underside of the penis.



In many cases, Monosomy 8p is also characterized by various structural malformations of the heart that are present at birth (congenital heart defects). Such defects may include an abnormal opening in the wall (septum) that separates the two lower or the two upper heart chambers (ventricular or atrial septal defects) or where the wall between the atria joins the wall between the ventricles (atrioventricular septal defect), allowing some oxygen-rich blood to recirculate through the lungs and potentially leading to rising blood pressure in the lungs (pulmonary hypertension).



In some cases, additional cardiac defects may be present, such as underdevelopment (hypoplasia) of the right ventricle; abnormal narrowing (stenosis) of the opening between the pulmonary artery and the right ventricle (pulmonary stenosis); and/or other abnormalities. (The pulmonary artery carries oxygen-depleted blood from the right ventricle to the lungs, where the exchange of oxygen and carbon dioxide occurs. The aorta, the major artery of the body, arises from the left ventricle and supplies oxygen-rich blood to most arteries.)



In those with congenital heart defects, associated symptoms and findings may vary, depending on the size, nature, and/or combination of heart malformations present and other factors. Some individuals may show no apparent symptoms (asymptomatic). However, in other cases, symptoms and findings may include difficulties feeding, poor growth, difficult or labored breathing (dyspnea), profuse sweating, recurrent lung infections, an impaired ability of the heart to pump blood efficiently to the lungs and the rest of the body (heart failure), bluish discoloration of the skin and mucous membranes (cyanosis), enlargement of the heart, and/or other abnormalities. In severe cases, congenital heart disease may lead to potentially life-threatening complications.

Causes

In cases of Chromosome 8, Monosomy 8p, there is deletion (monosomy) of an end (distal) portion of the short arm (p) of chromosome 8. "Distal" indicates away or farthest from a particular point of reference, meaning the chromosome's centromere (described below).



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," a long arm identified by the letter "q," and a narrowed region at which the two arms are joined (centromere). Chromosomes are further subdivided into bands that are numbered outward from the centromere. For example, the distal portion of the short arm of chromosome 8 (8p), sometimes referred to as "8p", includes bands 8p21 through 8p23; the end or "terminal" of 8p is known as "8pter".



In individuals with this chromosomal syndrome, the length and location of the monosomic region of 8p may vary, potentially affecting the range and severity of associated symptoms and findings. Reported cases have included deletions beginning within bands 8p21, 8p22, or 8p23 (breakpoint) that may extend to 8pter (i.e., terminal deletions) or may be interstitial. ("Interstitial" in this context means situated between, such as between other regions of a chromosome.) A few cases have also been reported in which certain, more "proximal" interstitial deletions of 8p may be associated with particular features characteristic of the syndrome. (Proximal, which is the opposite of the term distal, indicates closer to or nearest a particular point of reference [i.e., the centromere].)



Researchers have mapped a gene (known as "GATA4") to the short arm of chromosome 8 (8p23.1) that is thought to control expression of other genes involved in cardiac development. Evidence suggests that deficiency or disruption of GATA4 may contribute to certain congenital heart defects seen in some individuals with distal deletions of 8p involving 8p23.1. For example, in a study of patients with deletions of band 8p23.1, researchers demonstrated that affected individuals with associated heart defects had only one copy of the GATA4 gene, while another patient without known cardiac defects had both copies of the gene.



In most cases, Chromosome 8, Monosomy 8p appears to be caused by spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons (sporadically). In such instances, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.



Rare cases have also been reported that appear to result from a "balanced translocation" in one of the parents. Translocations occur when portions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. If a chromosomal rearrangement is balanced, meaning that it consists of an altered but balanced set of chromosomes, it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrier's offspring.



Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude the presence of a balanced translocation or other chromosomal rearrangement involving chromosome 8 in one of the parents.

Affected Populations

Chromosome 8, Monosomy 8p appears to affect males and females in relatively equal numbers. Since the disorder was originally described in 1973, over 20 cases have been reported in the medical literature.

Standard Therapies

Diagnosis

In some instances, the diagnosis of Chromosome 8, Monosomy 8p may be suggested 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 characteristic 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 analysis performed on such fluid or tissue samples may reveal the presence of Monosomy 8p2.



Chromosome 8, Monosomy 8p2 may be diagnosed and/or confirmed after birth (postnatally) by a thorough clinical evaluation, identification of characteristic physical findings, chromosomal analysis, and other specialized tests. A thorough cardiac evaluation may also be advised to detect any heart abnormalities that may be present. Such evaluation may include a thorough clinical examination; evaluation of heart and lung sounds with a stethoscope; x-ray studies; tests that record the electrical activities of heart muscle (electrocardiography [EKG]); a technique in which sound waves are directed toward the heart, enabling evaluation of cardiac motion and structure (echocardiogram); or other measures.



In turn, because congenital heart defects are commonly associated with Monosomy 8p, chromosomal analysis is suggested for all infants who are diagnosed with certain cardiac anomalies in association with facial malformations or an unusually small head (microcephaly) or both.



Treatment

The treatment of Chromosome 8, Monosomy 8p is directed toward the specific symptoms that are apparent in each individual. Such disease management may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; heart specialists (cardiologists); physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); and/or other health care professionals.



For affected individuals with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be required. In some cases, physicians may also recommend surgical repair or correction of certain craniofacial malformations, genital defects, and/or other malformations associated with the disorder. The specific surgical procedures performed will depend on the size, nature, severity, and combination of anatomical abnormalities, their associated symptoms, and other factors.



Early intervention services may also be important in ensuring that affected children reach their potential. Special services that may be beneficial include special remedial education, speech therapy, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for families of affected children. Other treatment for this disorder is symptomatic and supportive.

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

Buyse ML. Birth Defects Encyclopedia. Dover, Mass: Blackwell Scientific Publications, Inc; 1990:350.



Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:80.



JOURNAL ARTICLES

Gilmore L, et al. Deletion of 8p: a report of a child with normal intelligence. Dev Med Child Neurol. 2001;43:843-6.



de Vries BB, et al. Submicroscopic 8pter deletion, mild mental retardation, and behavioral problems caused by a familial t(8;20)(p23;p13). Am J Med Genet. 2001;99:314-19.



Devriendt K, et al. Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1. Am J Hum Genet. 1999;64:1119-26.



Bhatia SN, et al. Prenatal detection and mapping of a distal 8p deletion associated with congenital heart disease. Prenat Diagn. 1999;19:863-67.



Tsai CH, et al. A child with velocardiofacial syndrome and del(4)(q34.2): another critical region associated with a velocardiofacial syndrome-like phenotype. Am J Med Genet. 1999;82:336-39.



Pehlivan T, et al. GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart disease. Am J Med Genet. 1999;83:201-06.



Devriendt K, et al. Prenatal diagnosis of a terminal short arm deletion of chromosome 8 in a fetus with an atrioventricular septal defect. Prenat Diagn. 1998;18:65-67.



Johnson MC, et al. Chromosome abnormalities in congenital heart disease. Am J Med Genet. 1997;70:292-98.



Claeys I, et al. A recognisable behavioural phenotype associated with terminal deletions of the short arm of chromosome 8. Am J Med Genet. 1997;74:515-20.



Devriendt K, et al. Terminal deletion in chromosome region 8p23.1-8pter in a child with features of velo-cardio-facial syndrome. Ann Genet. 1995;38:228-30.



Tsukahara M, et al. Interstitial deletion of 8p: report of two patients and review of the literature. Clin Genet. 1995;48:41-45.



Pettenati MJ, et al. Molecular cytogenetic analysis of a familial 8p23.1 deletion associated with minimal dysmorphic features, seizures, and mild mental retardation. Hum Genet. 1992;89:602-06.



Hutchinson R, et al. Distal 8p deletion (8p23.1----8pter): a common deletion? J Med Genet. 1992;29:407-11.



Marino B, et al. Nonrandom association of atrioventricular canal and del (8p) syndrome. Am J Med Genet. 1992;42:424-27.



Pecile V, et al. Deficiency of distal 8p--report of two cases and review of the literature. Clin Genet. 1990;37:271-78.



Blennow E, et al. Partial monosomy 8p with minimal dysmorphic signs. J Med Genet. 1990;27:327-29.



Ostergaard GZ, et al. The 8p-syndrome. Ann Genet. 1989;32:87-91.



Fryns JP, et al. Normal phenotype and slight mental retardation in de novo distal 8p deletion (8pter----8p23.1:). Ann Genet. 1989;32:171-73.



Brocker-Vriends AH, et al. Monosomy 8p: an easily overlooked syndrome. J Med Genet. 1986;23:153-54.



Dobyns WB, et al. Deficiency of chromosome 8p21.1----8pter: case report and review of the literature. Am J Med Genet. 1985;22:125-34.



Patil SR, et al. Partial 8p- syndrome. J Genet Hum. 1980;28:123-29.



Reiss JA, et al. The 8p- syndrome. Hum Genet. 1979;47:135-40.



Bresson JL, et al. Partial deletion of the short arm of chromosome 8. Ann Genet. 1977;20:70-72.



Orye E, et al. A new chromosome deletion syndrome. Report of a patient with a 46,XY,8p- chromosome constitution. Clin Genet. 1976;9:289-301.



FROM THE INTERNET

Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 600576; 9/23/02. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600576.



Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 192430; 3/4/03. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?192430.

Resources

March of Dimes Birth Defects Foundation

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White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

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Fax: (202)534-3731

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TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.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/



American Heart Association

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Dallas, TX 75231

Tel: (214)784-7212

Fax: (214)784-1307

Tel: (800)242-8721

Email: Review.personal.info@heart.org

Internet: http://www.heart.org



UNIQUE - Rare Chromosome Disorder Support Group

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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/



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