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Chromosome 22 Ring

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 22 Ring

  • r(22)
  • Ring 22
  • Ring 22, Chromosome

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Chromosome 22 Ring is a rare disorder characterized by abnormalities of the 22nd chromosome. Associated symptoms and findings may be extremely variable from case to case. However, the disorder is typically associated with moderate to severe mental retardation. Some affected individuals may also have relatively mild, nonspecific physical (i.e., dysplastic) features, whereas others may have more distinctive, potentially severe physical abnormalities. According to reports in the medical literature, common findings include diminished muscle tone (hypotonia) and motor incoordination; an unsteady manner of walking (gait); pronounced verbal delays; and/or certain malformations of the skull and facial (craniofacial) region. Such craniofacial abnormalities may include an unusually small head (microcephaly); vertical skin folds that may cover the eyes' inner corners (epicanthal folds); unusually large ears; and/or other malformations. Chromosome 22 Ring is usually caused by spontaneous or "de novo" errors very early in the development of the embryo that appear to occur randomly for unknown reasons.

Symptoms

Chromosome 22 Ring is typically characterized by moderate to severe mental retardation associated with various physical findings that may range from relatively mild and nonspecific to more distinctive and potentially severe. Reports indicate that physical development and growth are normal in most affected individuals.

In addition to mental retardation, common features associated with Chromosome 22 Ring include low muscle tone (hypotonia); poor motor coordination; a clumsy, unsteady manner of walking (gait disturbances); and/or pronounced delays in the acquisition of speech and language comprehension. Some affected individuals may also have behavioral abnormalities, such as markedly increased motor activity with difficulties concentrating (hyperactivity) or autistic disorder. The latter may be characterized by deficient verbal and nonverbal communication skills, extreme social withdrawal, and a restricted range of interests and activities.

Many individuals with Chromosome 22 Ring also have malformations of the skull and facial (craniofacial) region. These commonly include an abnormally small head (microcephaly); a relatively long face; thick, low-set eyebrows; vertical skin folds that may cover the inner corners of the eyes (epicanthal folds); and/or large ears that may be low set. Some affected individuals may have additional craniofacial defects, such as a large, bulbous nose; thick, full lips; widely spaced eyes (ocular hypertelorism); and/or short, narrow eyelid folds (palpebral fissures). Other features have also been reported including drooping of the upper eyelids (ptosis), a highly arched roof of the mouth (palate), and/or a protruding tongue.

Some affected individuals may also have abnormalities of the hands and feet. Such abnormalities may include webbing or fusion (syndactyly) of certain fingers or toes, particularly the second and third toes; underdeveloped (hypoplastic) toenails; thin fingers; and/or unusually large hands and feet.

In rare cases, other physical abnormalities have been reported in association with Chromosome 22 Ring, such as structural malformations of the heart (congenital heart defects); kidney (renal) defects; partial or complete closure of the anal opening due to the presence of a thin membrane (imperforate anus); or an abnormal accumulation of lymph within certain tissues and associated swelling (lymphedema). (Lymph, a bodily fluid containing certain white blood cells, fats, and proteins, accumulates outside blood vessels in spaces between cells and drains or flows back into the bloodstream via lymph vessels. Lymphedema may result from disruption of lymph's normal drainage.)

In some cases, some of the features associated with Chromosome 22 Ring may resemble those seen in individuals with other disorders of chromosome 22, such as Chromosome 22 Monosomy or Cat Eye syndrome. (For further information on these chromosomal disorders, please see the "Causes" and "Related Disorders" sections of this report below.)

Causes

Chromosome 22 Ring results from loss (deletion) of genetic material from both ends of the 22nd chromosome and 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 22 Ring, associated symptoms and findings may be extremely variable, depending upon the amount and location of genetic material lost from the 22nd chromosome, the stability of the ring chromosome during subsequent cellular divisions (i.e., mitosis), and other factors. If the ring chromosome replaces a normal 22nd chromosome, symptoms may resemble those associated with Chromosome 22 Monosomy, a disorder characterized by deletion of all or a portion of the long arm of the 22nd chromosome. If cells contain a ring in addition to the normal chromosomal pair, certain features may be present that resemble those associated with another chromosomal disorder known as Cat Eye syndrome. (For further information on these chromosomal disorders, please see the "Related Disorders" section of this report below.)

Chromosome 22 Ring is usually caused by spontaneous or "de novo" errors very early in the development of the embryo. In such cases, the parents of an affected child typically have normal chromosomes, and the probability of having another child with the chromosomal abnormality is low. However, there have been reported cases in which Chromosome 22 Ring was inherited from a parent (familial transmission). In some familial cases, only a certain percentage of the parent's cells may contain Chromosome 22 Ring, whereas other cells may have a normal chromosomal makeup (a finding known as "chromosomal mosaicism"). Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude the presence of Chromosome 22 Ring or potential mosaicism in one of the parents.

Affected Populations

Based upon observed cases, Chromosome 22 Ring has appeared to affect females more frequently than males. Over 50 cases have been reported in the medical literature.

Related Disorders

Symptoms of the following disorders may be similar to those of Chromosome 22 Ring. Comparisons may be useful for a differential diagnosis:

Chromosome 22 Monosomy is a rare disorder characterized by absence (deletion or monosomy) of all or a portion of chromosome 22. In most cases, associated symptoms and findings are thought to result from monosomy of all or a part of the long arm (q) of the 22nd chromosome. Such abnormalities may be variable, depending upon the specific location of the chromosomal deletion. However, many affected individuals may have mental retardation, severe speech delays, growth retardation, diminished muscle tone (hypotonia), and/or craniofacial malformations. These may include an abnormally small head (microcephaly), large ears, a flat nasal bridge, widely spaced eyes (ocular hypertelorism), vertical skin folds that may cover the eyes' inner corners (epicanthal folds), and/or other findings. Individuals with the disorder may also have additional physical abnormalities, such as partial webbing or fusion of soft tissues of the toes (cutaneous syndactyly), heart defects, or sudden episodes of uncontrolled electrical activity in the brain (seizures). In some cases, Chromosome 22 Monosomy may also be characterized by underdevelopment (hypoplasia) or absence (agenesis) of the thymus and parathyroid glands. The thymus is thought to play an essential role in the immune system beginning during fetal development until puberty. The parathyroid glands are two pairs of small glands that produce parathyroid hormone, which helps to regulate calcium blood levels. In those with hypoplasia or agenesis of the thymus and parathyroid glands, associated findings may include abnormalities of the immune system (immunodeficiency), with impaired resistance to certain infections; a condition known as neonatal tetany characterized by low blood calcium levels (hypocalcemia), irritability, muscle twitching, tremors, and convulsions; and other abnormalities. Symptoms associated with neonatal tetany are typically present during the first days of life and are usually temporary. The association of agenesis or hypoplasia of the thymus and parathyroid glands, certain malformations of the heart and its major blood vessels, and craniofacial defects is often referred to as DiGeorge syndrome or DiGeorge sequence.

DiGeorge syndrome and Velocardiofacial Syndrome are disorders associated with a deletion at gene locus 22q11.2. (For further information, please choose "DiGeorge Syndrome" and "Velocardiofacial Syndrome" as your search terms in the Rare Disease Database.) An even rarer set of chromosomal disorders develops as a result of the deletion occurring at the far end (distal) of chromosome 22q13.3. The disorders associated with the deletion at distal 22q13 are characterized by developmental delays, normal to accelerated growth, speech delay, muscle weakness (myotonia), and mild structural defects (dysmorphism).

Cat Eye syndrome is a rare chromosomal disorder in which the short arm (p) and a small portion of the long arm (q) of chromosome 22 (22pter-22q11.2) are present three (trisomy) or four times (tetrasomy) rather than twice in cells of the body. Associated symptoms and findings may vary greatly in range and severity from case to case. Some individuals may have few, mild symptoms, whereas others may have multiple symptoms and findings that may include malformations of the craniofacial region, the digestive tract, the heart, and/or the kidneys. Abnormalities of the facial area may include a depressed nose; downwardly slanting eyelid folds (palpebral fissures); widely spaced eyes (ocular hypertelorism); absence of tissue from the colored portion of one or both eyes (unilateral or bilateral iris coloboma); a small jaw (micrognathia); and/or abnormal outgrowths of skin and small depressions in front of the outer ears (preauricular tags and pits). Some affected individuals may also have anal atresia, a malformation in which the rectum, which is the end portion of the large intestine, ends blindly. In such cases, an abnormal passage (fistula) may be present between the rectum and the vagina (rectovaginal fistula) or the region behind the external genitals (rectoperineal fistula). Additional physical malformations may also be present, such as structural abnormalities of the heart (cardiac defects); underdevelopment (hypoplasia) and/or absence (agenesis) of the kidneys; short stature; and/or other features. The disorder is often associated with mild to moderate mental retardation. (For further information, please choose "Cat Eye" as your search term in the Rare Disease Database.)

Other chromosomal disorders may have features similar to those potentially associated with Chromosome 22 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 22 Ring may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). 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, 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 Ring.

The diagnosis of Chromosome 22 Ring may be confirmed after birth (postnatally) based upon a thorough clinical evaluation, identification of characteristic physical findings, and chromosomal analysis. In some cases, specialized testing may also be conducted to detect certain abnormalities that may be associated with the disorder.

Treatment
The treatment of Chromosome 22 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, certain specialists, and/or other health care professionals.

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

Early intervention may be important in ensuring that children with Chromosome 22 Ring 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 individuals with Chromosome 22 Ring and their families.

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 22 Ring

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

References

TEXTBOOKS
Buyce ML., ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:287-288, 393-394, 961-962.

Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1997:68-69, 616-617.

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

REVIEW ARTICLES
MacLean JE, et al. Ring chromosome 22 and autism: report and review. Am J Med Genet. 2000;90:382-385.

Sovner R, et al. Ring chromosome 22 and mood disorders. J Intellect Disabil Res. 1996;40:82-86.

JOURNAL ARTICLES
Wenger SL, et al. Newborn infant with inherited ring and de novo interstitial deletion on homologous chromosome 22s. Am J Med Genet. 2000;91:351-354.

Gibbons G, et al. Ring chromosome 22 resulting in partial monosomy in a mentally retarded boy. Singapore Med J. 1999;40:273-275.

Frizzley JK, et al. Ring 22 duplication/deletion mosaicism: clinical, cytogenetic, and molecular characterisation. J Med Genet. 1999;36:237-241.

Mears AJ, et al. Minute supernumerary ring chromosome 22 associated with cat eye syndrome: further delineation of the critical region. Am J Hum Genet.
1995;57:667-673.

Severien C, et al. Ring chromosome 22: a case report. Klin Padiatr. 1991;203:467-469.

Gustavson KH, et al. Deleted ring chromosome 22 in a mentally retarded boy. Clin Genet. 1986;29:337-341.

Funderburk SJ, et al. Phenotypic variation in two patients with a ring chromosome 22. Clin Genet. 1979;16:305-310.

Fryns JP, et al. Ring chromosome 22 in a mentally retarded child and mosaic 45,XX,-15,-22,+t(15;22)(p11;q11)/46,XX,r(22)/46,XX karyotype in the mother. Hum Genet. 1979;47:213-216.

Hunter AG, et al. Phenotypic correlations in patients with ring chromosome 22. Clin Genet. 1977;12:239-249.

Veall RM, et al. A profoundly mentally handicapped woman with a ring chromosome 22. J Ment Defic Res. 1975;19:225-243.

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.

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

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