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