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 21 Ring is a rare chromosomal disorder in which the affected infant has a breakage of chromosome 21 at both ends, and the ends of the chromosome join together to form a ring. The amount of genetic material lost at the two ends of the chromosome may vary. As a result, an infant with very little absent genetic material may have no apparent symptoms while an infant with a significant part of the chromosomal ends missing may have many symptoms. When symptoms of the disorder are present, the affected infant may have mental retardation as well as abnormalities of the face, eyes, skeleton, and/or internal organs.
The symptoms and findings associated with Chromosome 21 Ring may be extremely variable, depending upon the amount and location of genetic material lost from the 21st chromosome and other factors. As a result, some individuals with Chromosome 21 Ring may have few or no associated symptoms, whereas others may have severe physical abnormalities and mental retardation.
In some cases, the features associated with Chromosome 21 Ring may resemble those seen in individuals with other disorders of chromosome 21, such as Chromosome 21 Monosomy or Down Syndrome (also known as Chromosome 21 Trisomy). (For further information on these chromosomal disorders, please see the “Causes” and “Related Disorders” sections of this report below.)
Additional features have also been reported in association with Chromosome 21 Ring, such as growth delays, abnormally diminished muscle tone (hypotonia), and malformations of the head and facial (craniofacial) area. For example, craniofacial abnormalities may include an unusually small head (microcephaly) or improper development of midfacial regions due to failed division of certain brain regions during embryonic development (holoprosencephaly). (For further information, please use “holoprosencephaly” as your search term in the Rare Disease Database.) Eye abnormalities may also be present, such as defective development (dysgenesis) of certain regions near the front of the eye (anterior segment); dislocation of the lens; or incomplete development (hypoplasia) of the nerve (i.e., optic nerve) that transmits impulses from the nerve-rich innermost layer of the eye (retina) to the brain. The degree of potential visual impairment depends upon the severity and combination of eye abnormalities present. Reports suggest that some individuals with Chromosome 21 Ring may also have an increased predisposition to respiratory, sinus, or other forms of infection. In addition, in some cases, other physical abnormalities may be present, such as skeletal defects or malformations of certain internal organs (visceral anomalies).
Although some individuals with Chromosome 21 Ring have normal intelligence, others may have varying levels of mental retardation. The disorder may also be characterized by delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation), including impaired speech and language skills.
According to reports in the medical literature, individuals with Chromosome 21 Ring, including those without any apparent symptoms, may have an increased incidence of infertility or pregnancy loss.
Chromosome 21 Ring results from loss (deletion) of genetic material from both ends of the 21st 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 21 Ring, associated symptoms and findings may be extremely variable, depending upon the amount and location of genetic material lost from the 21st chromosome and other factors. If the ring chromosome replaces a normal 21st chromosome, symptoms may resemble those associated with Chromosome 21 Monosomy, a disorder characterized by deletion of all or a portion of the 21st chromosome. If some cells contain a Chromosome 21 Ring in addition to the normal chromosomal pair (mosaic trisomy), some features may be present that resemble those associated with Down Syndrome (also known as Chromosome 21 Trisomy). (For further information on these chromosomal disorders, please see the “Related Disorders” section of this report below.)
Chromosome 21 Ring is usually caused by spontaneous or “de novo” errors very early during the development of the embryo. 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 a few reported cases in which Chromosome 21 Ring was inherited from a parent. In such cases, theoretically, the risk of transmitting the chromosomal abnormality from parent to offspring may be 50 percent for each pregnancy.
Chromosome 21 Ring is a rare chromosomal disorder that appears to affect males and females in equal numbers.
In some cases, a diagnosis of Chromosome 21 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 21 Ring.
The diagnosis of Chromosome 21 Ring may be confirmed after birth (postnatally) based upon a thorough clinical evaluation, 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. For example, in those with symptoms resembling those of Down Syndrome, careful monitoring and testing may be conducted to ensure early detection and prompt treatment of certain conditions potentially associated with Chromosome 21 Trisomy (e.g., congenital heart defects; certain infections; particular malignancies, such as leukemia; etc.).
The treatment of Chromosome 21 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 who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians, surgeons, certain specialists, and/or other health care professionals.
In some affected individuals, treatment may include surgical repair of certain craniofacial, skeletal, visceral, or other 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.
Treatment may also include measures to help prevent or aggressively treat infections. Other treatment is symptomatic and supportive.
Early intervention may be important in ensuring that children with Chromosome 21 Ring reach their potential. Special services that may be beneficial include special education, speech therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with Chromosome 21 Ring and their families.
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