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 18, Monosomy 18p is a rare chromosomal disorder in which all or part of the short arm (p) of chromosome 18 is deleted (monosomic). The disorder is typically characterized by short stature, variable degrees of mental retardation, speech delays, malformations of the skull and facial (craniofacial) region, and/or additional physical abnormalities. Associated craniofacial defects may vary greatly in range and severity from case to case. However, such features commonly include an unusually small head (microcephaly); a broad, flat nose; a "carp-shaped" mouth; large, protruding ears; widely spaced eyes (ocular hypertelorism); and/or other abnormalities. Rarely (i.e., in about 10 percent of cases), Monosomy 18p may be associated with holoprosencephaly, a condition in which the forebrain (prosencephalon) fails to divide properly during embryonic development. Holoprosencephaly may result in varying degrees of mental retardation, other neurologic findings, and/or extremely variable midline facial defects, such as the presence of a single, central front tooth (maxillary incisor); closely spaced eyes (hypotelorism); an abnormal groove in the upper lip (cleft lip); incomplete closure of the roof of the mouth (cleft palate); and/or, in severe cases, absence of the nose and/or cyclopia. Cyclopia is characterized by fusion of the eye cavities (orbits) into a single cavity containing one eye.
In some individuals with Monosomy 18p, additional physical abnormalities may be present. Such findings commonly include a short, webbed neck; a broad chest with widely spaced nipples; relatively small hands and feet; and/or an unusually small penis (micropenis) and/or undescended testes (cryptorchidism) in affected males.
Monosomy 18p is usually caused by spontaneous (de novo) errors very early in the development of the embryo that appear to occur randomly for unknown reasons (sporadically).
The symptoms and physical findings associated with Chromosome 18, Monosomy 18p may be variable from case to case. However, the syndrome is typically characterized by short stature, mental retardation, various malformations of the skull and facial (craniofacial) region, and/or additional physical abnormalities.
In many cases, infants with Monosomy 18p have a low birth weight, mild to moderate growth deficiency, and poor muscle tone (hypotonia). In addition, reports indicate that mental retardation is almost always present. The degree of mental deficiency may be extremely variable, ranging from borderline to severe; however, most are affected by moderate mental retardation. Many children also have severe delays in the acquisition of speech and language skills, with many not speaking simple words or sentences before approximately age seven to nine years. Some affected children may also have behavioral or emotional abnormalities, such as difficulties concentrating, restlessness, and rapidly changing moods (emotional lability).
As noted above, associated craniofacial abnormalities may be variable in range and degree. However, such malformations often include an abnormally small head (microcephaly); a distinctively round face (that may change with age to appear relatively long); a wide, “carp-shaped” mouth with downturning corners; a flattened or broad nose; and large, poorly formed, low-set ears. Many affected infants also have certain eye (ocular) abnormalities, such as widely spaced eyes (ocular hypertelorism); drooping upper eyelids (ptosis); vertical skin folds that may cover the eyes’ inner corners (epicanthal folds); and/or abnormal deviation of one eye in relation to the other (strabismus). Additional abnormalities may include an unusually small, retracted lower jaw (microretrognathia) and a potentially increased risk of tooth decay (dental caries).
In approximately 10 percent of individuals with Monosomy 18p, holoprosencephaly may be present. In those with this rare condition, the forebrain failed to normally divide into hemispheres during embryonic development. Holoprosencephaly may result in variable degrees of mental retardation, sudden episodes of uncontrolled electrical activity in the brain (seizures), and/or additional, variable neurologic findings; in extremely severe cases, potentially life-threatening complications may result during infancy or childhood. As noted earlier, holoprosencephaly may also result in various abnormalities of midfacial development. Reports suggest that some with the condition may have a normal or near normal facial appearance, while others may have relatively mild to extremely severe midline facial defects. In some affected individuals, associated malformations may include the presence of a single, central front tooth of the upper jaw (maxillary incisor); widely or closely set eyes (ocular hypertelorism or hypotelorism); an abnormal groove in the side or middle of the upper lip (lateral or median cleft lip); incomplete closure of the roof of the mouth (cleft palate); and/or, in extremely severe cases, fusion of the eye cavities (orbits) into a single cavity containing one eye (cyclopia). In addition, depending on the severity of defective midfacial development, nasal abnormalities may be present, such as an unusually flattened nose; a blind-ending, single-nostril nose; or absence of the nose (arhinia) and/or the presence of a tubular appendage above the orbit (proboscis). (For more information on this condition, choose “holoprosencephaly” as your search term in the Rare Disease Database.)
In some instances, Monosomy 18p may be characterized by other physical findings. Some affected infants may have an abnormal accumulation of fluid in soft tissues of the hands and feet, with associated swelling (lymphedema); a short, webbed neck; and/or an unusually broad chest with widely spaced nipples. Limb malformations may also be present, such as relatively small hands and feet; short fingers; abnormal deviation of the “pinkies” or fifth fingers (clinodactyly); and/or webbing or fusion (syndactyly) of certain toes. In affected males, physical features may include an unusually small penis (micropenis) and/or undescended testes (cryptorchidism). Additional features have also been reported in association with Monosomy 18p in some cases, such as deficiency of a particular antibody (i.e., immunoglobulin A [IgA]) that helps the body to fight certain infections; abnormal absence of scalp hair (alopecia) beginning during infancy; and/or other findings. In addition, according to researchers, various structural malformations of the heart (congenital heart defects) may be present in up to five percent of cases.
Chromosome 18, Monosomy 18p is a chromosomal abnormality in which there is deletion (monosomy) of all or a portion of the short arm (p) 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.
Monosomy 18p usually 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, other cases have been reported in which Monosomy 18p has appeared to result from a “balanced translocation” in one of the parents. 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.
In addition, in some rare cases, a parent of an affected child has also had deletion of the short arm of chromosome 18 in all or some cells. (Cases in which only a percentage of an individual’s cells has the chromosomal abnormality while other cells have a normal chromosomal make-up are known as “mosaicism.”)
Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude the presence of potential mosaicism or a balanced translocation in one of the parents.
Chromosome 18, Monosomy 18p appears to affect females more frequently than males by a ratio of approximately three to two. Reports indicate that the mean parental age is older than average for the mothers and fathers of children with Monosomy 18p (i.e., age 32 years and 38 years, respectively). Since Monosomy 18p was originally described in 1963, over 120 cases have been reported in the medical literature.
In some cases, Chromosome 18, Monosomy 18p 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 18p.
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 conducted to help detect and/or characterize certain abnormalities that may be associated with the disorder.
The treatment of Chromosome 18, Monosomy 18p 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; physicians who specialize in disorders of the skeleton, muscles, joints, and related tissues (orthopedists); neurologists; speech-language pathologists; and/or other health care professionals.
In some cases, physicians may recommend surgical repair of certain craniofacial, skeletal, ocular, and/or other defects potentially associated with the disorder. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.
Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, speech therapy, 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
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, holoprosencephaly, etc.].)
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Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:52-53, 573-80.
Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:381-83, 876-77.
Tsukahara M, et al. Familial del(18p) syndrome. Am J Med Genet. 2001;99:67-69.
Taine L, et al. 18p monosomy with midline defects and a de novo satellite identified by FISH. Ann Genet. 1997;40:158-63.
Velagaleti GV, et al. Familial deletion of chromosome 18 (p11.2). Ann Genet. 1996;39:201-04.
Gocke H, et al. The fetal phenotype of the 18p-syndrome. Report of a male fetus at twenty-one weeks. Ann Genet. 1988;31:60-64.
Carratu A, et al. Monosomy 18p syndrome with holoprosencephaly. Minerva Pediatr. 1983;35:1225-28.
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