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 6 Ring is a rare disorder in which there is loss (deletion) of chromosomal material from both ends of the 6th chromosome and joining of the ends to form a ring. Associated symptoms and findings may vary greatly, depending upon the amount and location of lost chromosomal material and other factors. For example, there have been some reported cases in which children with Chromosome 6 Ring have few physical abnormalities and normal intelligence. However, many with the chromosomal abnormality are affected by growth retardation; varying degrees of mental retardation; mild to severe delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation); and/or various abnormalities of the skull and facial (craniofacial) region. Such craniofacial features often include an unusually small head (microcephaly), malformed or low-set ears, and/or a small jaw (micrognathia). Eye (ocular) defects are also relatively common, such as drooping of the upper eyelids (ptosis), unusually small eyes (microphthalmia), abnormal deviation of one eye in relation to the other (strabismus), and/or other findings. Chromosome 6 Ring usually appears to result from spontaneous (de novo) errors very early in the development of the embryo that occur for unknown reasons (sporadically).
As noted above, associated symptoms and physical features may vary greatly in range and severity. Some cases have been reported in which children with Chromosome 6 Ring have normal intelligence and minimal physical abnormalities. However, others with the chromosomal abnormality may be affected by multiple characteristic features of the disorder. Such features frequently include growth retardation before and after birth (prenatal and postnatal growth retardation) and associated short stature; poor muscle tone (hypotonia), psychomotor delays, and mild to profound mental retardation; craniofacial malformations; and/or ocular defects. In some cases, additional physical abnormalities may also be present.
Craniofacial malformations commonly associated with Chromosome 6 Ring include an unusually small head (microcephaly); low-set or malformed (dysplastic) ears; a small jaw (micrognathia); a flat nasal bridge; widely spaced eyes (ocular hypertelorism); and/or vertical skin folds (epicanthal folds) that may cover the eyes’ inner corners. Some affected individuals may also have a highly arched roof of the mouth (palate); a short neck that may be webbed or have excessive (redundant) skin; and/or other craniofacial abnormalities.
Chromosome 6 Ring is also frequently associated with additional ocular defects. These may include drooping of the upper eyelids (ptosis); unusually small eyes (microphthalmia); partial absence of ocular tissue from the colored region of the eyes (iris coloboma); abnormal deviation of one eye in relation to the other (strabismus); and/or involuntary, rapid, rhythmic eye movements (nystagmus). In some cases, other ocular abnormalities may be present, such as absence of the iris (aniridia); unusual largeness of the transparent region forming the front of the eyeball (megalocornea); elevated pressure of the fluid in the eye (glaucoma); and/or degenerative changes of the optic nerve (optic atrophy). (The optic nerve, also known as the second cranial nerve, transmits impulses from the innermost membrane at the back of the eye [retina] to the brain.) The degree of potential visual impairment depends upon the severity and/or combination of ocular defects present.
Additional physical abnormalities have been reported in association with Chromosome 6 Ring. Such findings have included foot deformities (clubfoot); hip dislocation; widely spaced nipples; structural abnormalities of the heart (congenital heart defects); and/or other defects. In addition, in some cases, neurologic abnormalities may be present, such as absence of the thick band of nerve fibers normally joining the two hemispheres of the brain (agenesis of the corpus callosum); sudden episodes of uncontrolled electrical activity in the brain (seizures); and/or hydrocephalus. Hydrocephalus refers to obstructed flow or impaired absorption of cerebrospinal fluid (CSF), resulting in abnormal accumulation of CSF in the skull, usually under increased pressure. (CSF is the protective fluid that circulates through the four cavities [ventricles] of the brain, the canal containing the spinal cord [spinal canal], and the space between layers of the protective membranes [meninges] surrounding the brain and spinal cord [i.e., subarachnoid space].) During infancy or early childhood, hydrocephalus may be associated with rapid enlargement of the head (since bones of the skull have not yet fused); in addition, other findings may include difficulties feeding, vomiting, irritability, lack of normal reflex responses, severe drowsiness, seizures, and potentially life-threatening complications without treatment.
Chromosome 6 Ring results from deletion (monosomy) of chromosomal material from the long arm (q) and short arm (p) of chromosome 6 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,” 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.
As noted previously, in individuals with Chromosome 6 Ring, associated symptoms and findings may be extremely variable. Such clinical variability may depend upon the amount and specific location of material lost from the 6th chromosome, the stability of the ring chromosome during subsequent cellular divisions, the percentage of cells with the ring chromosome, and/or other factors. Evidence suggests that the ring chromosome typically appears to replace a normal 6th chromosome. In addition, in some cases, the abnormal chromosome within certain cells may have two centromeres (dicentric rings) or other structural abnormalities. As mentioned above, only a certain percentage of an affected individual’s cells may have Chromosome 6 Ring abnormalities, while other cells may have a normal chromosomal makeup (a finding known as “chromosomal mosaicism”), affecting the variability of associated symptoms and findings.
In most cases, Chromosome 6 Ring appears to be caused by spontaneous (de novo) errors very early in embryonic development. 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. However, chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude the presence of certain chromosomal abnormalities in one of the parents, such as Chromosome 6 Ring, potential mosaicism, or a “balanced translocation” involving chromosome 6. (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.)
Since Chromosome 6 Ring was originally described, approximately 23 cases have been reported in the medical literature. In observed cases, males appear to be affected slightly more frequently than females.
In some cases, Chromosome 6 Ring 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 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 Chromosome 6 Ring.
The disorder may be diagnosed or confirmed after birth (postnatally) based upon thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. Additional specialized tests may also be performed to help detect and/or characterize certain abnormalities that may be associated with the disorder.
The treatment of Chromosome 6 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; eye specialists; physicians who specialize in neurologic disorders (neurologists), heart abnormalities (cardiologists), or disorders of the skeleton, muscles, joints, and related tissues (orthopedists); physical therapists; and/or other health care professionals.
For some affected individuals, physicians may recommend surgical repair of certain craniofacial, ocular, and/or other malformations 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.
In affected individuals with hydrocephalus, shunting may be required to remove excess cerebrospinal fluid (CSF). Shunts are specialized devices that drain excess CSF away from the brain to another part of the body for absorption into the bloodstream.
For individuals affected by seizures, treatment may include the administration of anticonvulsant medications to help prevent, reduce, or control seizures.
Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical 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.
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: [email protected]
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, craniofacial abnormalities, ocular defects, etc.].)
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