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 18q- syndrome (also known as Chromosome 18, Monosomy 18q) is a rare chromosomal disorder in which there is deletion of part of the long arm (q) of chromosome 18. Associated symptoms and findings may vary greatly in range and severity from case to case. However, characteristic features include short stature; mental retardation; poor muscle tone (hypotonia); malformations of the hands and feet; and abnormalities of the skull and facial (craniofacial) region, such as a small head (microcephaly), a "carp-shaped" mouth, deeply set eyes, prominent ears, and/or unusually flat, underdeveloped midfacial regions (midfacial hypoplasia). Some affected individuals may also have visual abnormalities, hearing impairment, genital malformations, structural heart defects, and/or other physical abnormalities. Chromosome 18q- syndrome usually appears to result from spontaneous (de novo) errors very early during embryonic development that occur for unknown reasons (sporadically).
As noted above, associated symptoms and findings may vary from case to case. However, many infants with the disorder have a low birth weight and growth delays after birth, resulting in short stature. In addition, Chromosome 18q- syndrome is often characterized by low muscle tone (hypotonia); sudden episodes of uncontrolled electrical activity in the brain (seizures); moderate to severe delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation); and varying degrees of mental retardation. Evidence suggests that most individuals with the disorder are affected by profound, severe, or moderate mental retardation. However, mild mental deficiency has been reported in some cases. In addition, some affected children may have behavioral problems, such as abnormally increased activity (hyperactivity), aggressive behavior, and tantrums.
Chromosome 18q- syndrome is also typically associated with malformations of the skull and facial (craniofacial) region. Characteristic craniofacial findings may include an unusually small head (microcephaly); flat, underdeveloped (hypoplastic) midfacial regions; deeply set eyes; a “carp-shaped” mouth; and/or relative protrusion of the lower jaw (mandibular prognathism). Some affected individuals may also have a broad nasal bridge; incomplete closure (clefting) or unusual narrowness of the roof of the mouth (palate); and/or an abnormal groove in the upper lip (cleft lip).
Chromosome 18q- syndrome is also often characterized by additional eye (ocular) defects, such as vertical skin folds that may cover the eyes’ inner corners (epicanthal folds); involuntary, rhythmic, rapid eye movements (nystagmus); and/or abnormal deviation of one eye in relation to the other (strabismus). Associated ocular defects may also include abnormally small eyes (microphthalmia); partial absence of ocular tissue from the colored region of the eyes (coloboma of the iris); clouding of the normally transparent front region of the eyes (corneal opacities); defects of the retinas and optic disks; and/or other ocular abnormalities. (The retina is the nerve-rich membrane upon which images are focused at the back of the eye; its specialized nerve cells convert light into nerve impulses that are transmitted to the brain via the optic nerve. The optic disk, also known as the “blind spot,” is the region where fibers of the retina become part of the optic nerve.) Such ocular defects may result in varying degrees of visual impairment.
Some individuals with Chromosome 18q- syndrome may also have malformations of the ears. These may include unusually prominent ears and/or abnormally narrow (stenotic) or absent (atretic) external ear canals, with associated hearing impairment.
Chromosome 18q- syndrome is also often associated with distinctive abnormalities of the hands and feet, including long, thin, tapered hands; abnormal skin ridge patterns on the fingers and palms; abnormal placement of the thumbs and certain toes; and/or deformities in which the feet are twisted out of shape or position (clubfeet). Some affected individuals may also have rib malformations, hip deformities, and/or other skeletal defects. In addition, abnormal dimples may be present in certain regions, including over the knuckles and the sides of the knees.
Individuals with Chromosome 18q- syndrome may also have genital abnormalities. In affected females, there may be underdevelopment of the skin folds surrounding the vaginal opening (hypoplastic labia). In males with the disorder, genital malformations may include undescended testes (cryptorchidism); an abnormally small penis (micropenis) and scrotum; and/or abnormal placement of the urinary opening (hypospadias), such as on the underside of the penis.
Additional physical abnormalities have also been reported in association with the disorder, such as widely spaced nipples; deficiency of a particular antibody (i.e., immunoglobulin A [IgA]) that helps the body to fight certain infections; kidney (renal) defects; and/or other findings. In addition, in over 30 percent of cases, congenital heart defects may be present. Such heart defects have included an abnormal opening in the fibrous partition (septum) that normally separates the upper chambers (atria) or the lower chambers (ventricles) of the heart (atrial or ventricular septal defects); abnormal narrowing (stenosis) of the opening between the pulmonary artery and the right ventricle (pulmonary stenosis); or patent ductus arteriosus (PDA). In PDA, the channel that is present between the pulmonary artery and the aorta during fetal development fails to close after birth. (The pulmonary artery transports oxygen-poor blood from the right ventricle to the lungs, where the exchange of oxygen and carbon dioxide occurs. The aorta, the major artery of the body, arises from the left ventricle and supplies oxygen-rich blood to most arteries.) In some individuals with Chromosome 18q- syndrome, additional physical abnormalities may also be present.
Chromosome 18q- syndrome is a chromosomal disorder in which there is deletion (monosomy) of part of the long arm (q) of chromosome 18. 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. For example, “18q21” refers to band 21 of the long arm of chromosome 18.
Evidence suggests that individuals with characteristic features of the disorder have deletions from within band 18q21 (e.g., 18q21.3) or 18q22 (e.g., 18q22.2) that may extend to the end (or “terminal”) of chromosome 18q (qter). In some cases, the deletion could be interstitial; that is, in the middle of the chromosome. In addition, in some cases, only a certain percentage of an affected individual’s cells may have the deletion, while other cells may have a normal chromosomal makeup (a finding known as “chromosomal mosaicism”). The range and severity of symptoms may depend on the specific size of the deletion and the percentage of cells with the chromosomal abnormality. Reports suggest that those with 18q- mosaicism tend to have less severe symptoms and findings.
In most cases, Chromosome 18q- syndrome 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.
Less commonly, the deletion may result from a “balanced translocation” in one of the parents. Translocations occur when portions 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.
Rare cases have also been reported in which the disorder has appeared to result from a parental chromosomal inversion or other chromosomal rearrangements. An inversion is characterized by breakage of a chromosome in two places and reunion of the segment in the reverse order.
Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude the presence of a balanced translocation or other chromosomal rearrangement in one of the parents.
Chromosome 18q- syndrome appears to affect females more frequently than males by a ratio of approximately three to two. Since the disorder was originally reported in the medical literature in 1964, more than 80 cases have been recorded.
In some cases, Chromosome 18q- syndrome 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 developmental 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 Monosomy 18q.
The disorder is usually diagnosed or confirmed after birth (postnatally) based upon a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. 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 18q- syndrome is directed toward the specific symptoms that are apparent in each individual. Such disease management may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; neurologists; eye specialists; hearing specialists; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); heart specialists (cardiologists); and/or other health care professionals.
In some cases, physicians may recommend surgical correction of certain craniofacial, skeletal, genital, 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 required. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.
For individuals with ocular abnormalities, corrective lenses, surgery, and/or other measures may be advised to help improve vision in some cases. In addition, in those with hearing impairment, recommended treatment may include surgical measures and/or the use of specialized hearing aids or additional supportive techniques that may aid communication.
In some cases, anticonvulsant medications may be administered to help prevent, reduce, or control seizures. In addition, for individuals with low levels of certain antibodies (i.e., IgA deficiency), disease management may include regular monitoring and appropriate, supportive measures to help prevent and aggressively treat infections.
Early intervention may also 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
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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, congenital heart defects, craniofacial abnormalities, ocular defects, hearing impairment, etc.].)
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