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Chromosome 15 Ring

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 1993, 1997, 2001, 2003, 2009

NORD is very grateful to Shashikant Kulkarni, PhD, Director of CytoGenomics and Molecular Pathology, Director of Clinical & Molecular Cytogenetics, Department of Pathology, Washington University School of Medicine, for assistance in the preparation of this report.

Synonyms of Chromosome 15 Ring

Disorder Subdivisions

General Discussion

Chromosome 15 Ring results from loss (deletion) of genetic material from both ends of the 15th chromosome and a joining of the ends to form a ring. 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.

In individuals with Chromosome 15 Ring, the variability of associated symptoms and findings may depend upon the amount and location of genetic material lost from the 15th chromosome, the stability of the ring chromosome during subsequent cellular divisions, or other factors. Evidence suggests that the clinical features seen in Chromosome 15 Ring appear to result from deletions of genetic material from the long arm (q) of chromosome 15 (known as "monosomy 15q"), with the ring chromosome typically replacing a normal 15th chromosome. In addition, in some cases, only a certain percentage of an individual's cells may contain Chromosome 15 Ring, while other cells may have a normal chromosomal makeup (a finding known as "chromosomal mosaicism"), potentially affecting the variability of associated symptoms and findings.

In most cases, Chromosome 15 Ring appears to be caused by spontaneous (de novo) errors very early in embryonic development. 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 of an affected individual also has Chromosome 15 Ring. In such instances, the chances are greater of having another child with the chromosomal abnormality. In addition, a few cases have been reported in which Chromosome 15 Ring has been the result of a "balanced translocation" in one of the parents. Translocations occur when regions 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 Chromosome 15 Ring, potential mosaicism, or a balanced translocation in one of the parents.

Many individuals with Chromosome 15 Ring have some features similar to those associated with Russell-Silver syndrome (RSS), which is a genetic disorder characterized by growth deficiency and short stature, distinctive facial abnormalities, and other features. (For further information, please see the "Related Disorders" section below.) In some of these cases, genetic analysis has indicated that the prenatal and postnatal growth retardation associated with Chromosome 15 Ring (and potentially suggestive of RSS) may result from deletion of a gene known as the insulin-like growth factor I receptor (IGF1R) gene, which has been mapped to the long arm of chromosome 15 (15q25-q26).

Symptoms

Although associated features may be variable, Chromosome 15 Ring is commonly characterized by growth delays before and after birth, resulting in short stature (dwarfism); varying degrees of mental retardation; low muscle tone (hypotonia); craniofacial malformations; and limb abnormalities.

According to reports in the medical literature, Chromosome 15 Ring is often associated with mild to moderate mental retardation. However, in some instances, severe mental retardation may become evident during adulthood. In addition, some affected infants and children may have delays in the acquisition of language and speech.

In many individuals with Chromosome 15 Ring, craniofacial malformations may result in a distinctive facial appearance. Such abnormalities may include an unusually small head (microcephaly) with a prominent forehead (frontal bossing); a "triangular-shaped" face; widely spaced eyes (ocular hypertelorism); a high, broad nasal bridge; and/or malformed outer ears.

Many affected individuals may also have abnormalities of the hands and feet. These may include delayed bone age; abnormal shortness of certain bones of the fingers and toes (phalanges), causing the hands and feet to appear short; abnormal deviation (clinodactyly) of the "pinkies" or fifth fingers; and/or underdevelopment (hypoplasia) of the thumbs.

In many affected males, decreased functioning of the testes (hypogonadism) results in infertility. However, reports suggest that gonadal (i.e., ovarian) function, sexual development, and fertility appear to be normal in most affected females.

In some cases, Chromosome 15 Ring may be associated with additional physical findings. Such abnormalities may include structural malformations of the heart that are present at birth (congenital heart defects), kidney (renal) defects, and/or congenital dislocation of the hips. In addition, some affected individuals may have light brown, pale tan, or "coffee-colored" patches on the skin (cafe-au-lait spots).

Causes

Chromosome 15 Ring results from loss (deletion) of genetic material from both ends of the 15th chromosome and a joining of the ends to form a ring. Chromosomes are found in the nucleus of all body cells except red blood 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.

In individuals with Chromosome 15 Ring, the variability of associated symptoms and findings may depend upon the amount and location of genetic material lost from the 15th chromosome, the stability of the ring chromosome during subsequent cellular divisions, or other factors. Evidence suggests that the clinical features seen in Chromosome 15 Ring appear to result from deletions of genetic material from the long arm (q) of chromosome 15 (known as "monosomy 15q"), with the ring chromosome typically replacing a normal 15th chromosome. In addition, in some cases, only a certain percentage of an individual's cells may contain Chromosome 15 Ring, while other cells may have a normal chromosomal makeup (a finding known as "chromosomal mosaicism"), potentially affecting the variability of associated symptoms and findings.

In most cases, Chromosome 15 Ring appears to be caused by spontaneous (de novo) errors very early in embryonic development. 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 of an affected individual also has Chromosome 15 Ring. In such instances, the chances are greater of having another child with the chromosomal abnormality. In addition, a few cases have been reported in which Chromosome 15 Ring has been the result of a "balanced translocation" in one of the parents. Translocations occur when regions 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 unbalanced chromosome inheritance by 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 Chromosome 15 Ring, potential mosaicism, or a balanced translocation in one of the parents.

Many individuals with Chromosome 15 Ring have some features similar to those associated with Russell-Silver syndrome (RSS), which is a genetic disorder characterized by growth deficiency and short stature, distinctive facial abnormalities, and other features. (For further information, please see the "Related Disorders" section below.) In some of these cases, genetic analysis has indicated that the prenatal and postnatal growth retardation associated with Chromosome 15 Ring (and potentially suggestive of RSS) may result from deletion of a gene known as the insulin-like growth factor I receptor (IGF1R) gene, which has been mapped to the long arm of chromosome 15 (15q25-q26).

Affected Populations

Since Chromosome 15 Ring was originally described, at least 25 cases have been recorded in the medical literature. In such observed cases, females appear to be affected more frequently than males.

Related Disorders

Symptoms of the following disorders may be similar to those of Chromosome 15 Ring. Comparisons may be useful for a differential diagnosis:

Russell-Silver syndrome (RSS) is a rare genetic disorder characterized by growth delays before and after birth, leading to short stature (dwarfism); overgrowth of one side of the body (hemihypertrophy) that may affect the head, trunk, arms, and/or legs; distinctive craniofacial features; and other physical abnormalities. Characteristic craniofacial malformations may include a "triangular-shaped" face with a small, pointed chin; a prominent forehead (frontal bossing); bluish discoloration of the "whites" of the eyes (blue sclera); an unusually small, wide mouth with downwardly turned corners; and/or a small jaw (micrognathia). In some cases, additional physical abnormalities may include abnormal deviation or "incurving" (clinodactyly) of the fifth fingers; webbing or fusion (syndactyly) of certain toes; underdevelopment (hypoplasia) of bones of the fingers (phalanges); coffee-colored patches on the skin (cafe-au-lait spots); and/or abnormalities of the kidneys and urinary tract. In addition, although most affected individuals have normal intelligence, mild mental retardation may sometimes be present. In most cases, RSS is thought to result from new genetic changes (mutations) that occur randomly for unknown reasons (sporadically). Less commonly, it appears that the disorder may be inherited as an autosomal recessive trait. In addition, a rare form of RSS has been identified that is thought to be inherited as an X-linked dominant trait.

As mentioned above, RSS and Chromosome 15 Ring may share several features, including growth retardation and short stature, a triangular-shaped face, finger (digital) abnormalities, cafe-au-lait spots, and other abnormalities. Reports indicate that certain features are typically more marked in those with Chromosome 15 Ring, such as mental retardation, smallness of the head (microcephaly) and other facial abnormalities, congenital heart defects, and digital malformations. Thus, experts suggest that the presence of such findings in association with RSS features should lead to chromosomal analysis to help confirm or exclude the presence of Chromosome 15 Ring. (For further information, choose "Russell Silver" as your search term in the Rare Disease Database.)

Additional chromosomal disorders may have features similar to those associated with Chromosome 15 Ring. Chromosomal testing is necessary to confirm the specific chromosomal abnormality present. (For further information on such disorders, choose the name of the specific chromosomal disorder in question or use "chromosome" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
In some cases, a diagnosis of Chromosome 15 Ring may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, 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 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 the fluid or tissue samples may reveal the presence of Chromosome 15 Ring.

The disorder may also be diagnosed or confirmed soon after birth, during infancy, or later during childhood based upon a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. Specialized tests may also be conducted to help detect and/or characterize certain abnormalities that may be associated with the disorder. Such testing may include advanced imaging techniques (e.g., to assess skeletal abnormalities, renal malformations, etc.); studies to evaluate the structure and function of the heart (e.g., x-ray imaging, electrocardiogram [EKG], echocardiogram); and/or other diagnostic studies.

Treatment
The treatment of Chromosome 15 Ring 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); physicians who diagnose and treat heart abnormalities (cardiologists); speech-language pathologists; physical therapists; and/or other health care professionals.

For some affected individuals, treatment may include surgical repair of certain craniofacial or other malformations potentially 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, speech 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.

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

Organizations related to Chromosome 15 Ring

(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., mental retardation, short stature, craniofacial abnormalities, congenital heart defects, etc.].)

References

TEXTBOOKS
Behrman RE, et al., eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:317.

Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:89-90.

Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:375-76.

JOURNAL ARTICLES
Matsuishi T, et al. Ring chromosome 15 syndrome in an adult female. J Intellect Disabil Res. 1996;40:478-80.

Rogan PK, et al. Distinct 15q genotypes in Russell-Silver and ring 15 syndromes. Am J Med Genet. 1996;62:10-15.

Tamura T, et al. Ring chromosome 15 involving deletion of the insulin-like growth factor 1 receptor gene in a patient with features of Silver-Russell syndrome. Clin Dysmorphol. 1993;2:106-13.

Horigome Y, et al. Familial occurrence of ring chromosome 15. Clin Genet. 1992;41:178-80.

Smith A, et al. Ring chromosome 15 and 15qs+ mosaic: clinical and cytogenetic behaviour spanning 29 years. Am J Med Genet. 1991;40:460-63.

Butler MG, et al. Two patients with ring chromosome 15 syndrome. Am J Med Genet. 1988;29:149-54.

Fryns JP, et al. Ring chromosome 15 syndrome. Further delineation of the adult phenotype. Ann Genet. 1986;29:45-48.

Wilson GN, et al. Phenotypic delineation of ring chromosome 15 and Russell-Silver syndrome. J Med Genet. 1985;22:233-36.

Fryns JP, et al. Ring chromosome 15 syndrome. Acta Paediatr Belg. 1981;34:47-49.

Malygina NA, et al. Chromosomal mosaicism in the r(15) syndrome. Genetika. 1980;16:2029-33.

Fryns JP, et al. Ring chromosome 15 syndrome. Hum Genet. 1979;51:43-48.

Scheibenreiter S, et al. Ring chromosome 15 in a child. Wien Klin Wochenschr. 1978;90:22-25.

Rumenic L, et al. Ring chromosome 15 in child with a minor dysmorphism of phenotype. Hum Genet. 1976;33:187-88.

FROM THE INTERNET
Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 180860; 10/5/00. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?180860.

Report last updated: 2009/04/10 00:00:00 GMT+0