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Congenital spondyloepiphyseal dysplasia is a rare genetic disorder characterized by growth deficiency before birth (prenatally), spinal malformations, and/or abnormalities affecting the eyes. As affected individuals age, growth deficiency eventually results in short stature (dwarfism) due, in part, to a disproportionately short neck and trunk, and a hip deformity in which the thigh bone is angled toward the center of the body (coxa vara). In most cases, affected individuals may have diminished muscle tone (hypotonia), abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis), abnormal inward curvature of the spine (lumbar lordosis), and/or unusual protrusion of the breast bone (sternum), a condition known as pectus carinatum. Affected individuals also have abnormalities affecting the eyes including nearsightedness (myopia) and, in approximately 50 percent of cases, detachment of the nerve-rich membrane lining the eye (retina). Congenital spondyloepiphyseal dysplasia is inherited as an autosomal dominant trait.
Congenital spondyloepiphyseal dysplasia is characterized by growth deficiency that occurs before birth (prenatally), spinal malformations, and/or abnormalities of the eyes. Growth deficiencies continue after birth and throughout childhood, resulting in short stature (dwarfism). Short stature also results, in part, due to a disproportionately short neck and trunk, and a hip deformity in which the thighbone is angled toward the center of the body (coxa vara). In most cases, affected infants also exhibit diminished muscle tone (hypotonia), muscle weakness, and/or stiffness.
In most cases, affected individuals have spinal malformations including abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis), abnormal inward curvature of the spine (lumbar lordosis). Stiffness and diminished joint mobility at the knees, elbows, and hips may be present. Hypotonia, muscle weakness, and spinal malformations may result in a delay in affected children learning to walk. In some cases, affected children may exhibit an unusual "waddling" walk (gait).
In most cases, affected individuals develop progressive nearsightedness (myopia) and, in approximately 50 percent of cases, detachment of the nerve-rich membrane lining the eye (retina). In some cases, affected individuals also have an abnormally flat face, underdevelopment of the cheek bone (malar hypoplasia), and/or incomplete closure of the roof of the mouth (cleft palate).
Additional abnormalities associated with congenital spondyloepiphyseal dysplasia may include underdevelopment of the stomach (abdominal) muscles; a rounded, bulging chest (barrel chest) with an unusually prominent breast bone (sternum), a condition known as pectus carinatum; and/or the heel of the foot may be turned inward toward body while the rest of the foot is bent downward and inward (talipes equinovarus or clubfoot). In rare cases, affected individuals may exhibit hearing impairment due to abnormalities of the inner ear (sensorineural hearing loss).
Some researchers have separated congenital spondyloepiphyseal dysplasia into two types. In one type, affected individuals have more severe short stature and hip abnormalities. Affected individuals with the second type are taller and have milder hip malformations.
Congenital spondyloepiphyseal dysplasia is inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.
A variety of mutations (e.g., deletions, duplications, etc.) involving the COL2A1 gene, which codes for Type II collagen, may lead to the development of congenital spondyloepiphyseal dysplasia. Collagen is the major protein of bone and connective tissue including the skin, tendons, and sclera.
Congenital spondyloepiphyseal dysplasia affects males and females in equal numbers. One estimate placed the number of cases at 1 per 100,000 live births.
Symptoms of the following disorders can be similar to those of congenital spondyloepiphyseal dysplasia. Comparisons may be useful for a differential diagnosis:
Pseudoachondroplastic dysplasia is a rare inherited disorder characterized by skeletal malformations resulting in short legs and mild to moderate short stature (short-limbed dwarfism). Affected individuals may have short, stubby fingers (brachydactyly), abnormally bowed legs (genu varum), and/or a malformation in which the knees are abnormally close together and the ankles are unusually far apart (genu valgum). In addition, affected individuals may have spinal abnormalities including increased curvature of the bones of the lower spine (lumbar lordosis) and front-to-back curvature of the spine (kyphosis). In some cases, the wrist may abnormally flexed toward the pinky side of the hand (ulnar deviation of the wrist) and the elbows and hips may have limited flexibility. Cases of pseudoachondroplastic dysplasia are due to mutations of the COMP gene, meaning that this disorder is allelic to some cases of multiple epiphyseal dysplasia (i.e., caused by different mutations of the same disease gene.) Pseudochondroplastic dysplasia is inherited as an autosomal dominant trait.
Spondyloepiphyseal dysplasia tarda, X-linked, is a rare genetic disorder that primarily affects males, and is characterized by short stature (dwarfism) and abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis), abnormal inward curvature of the spine (lumbar lordosis). Affected individuals may also have a short neck, flat facies, and a rounded, bulging chest (barrel chest) with an unusually prominent breast bone (sternum), a condition known as pectus carinatum. Evidence of abnormal growth in this X-linked recessive inherited disorder only becomes evident at five to 10 years of age. (For more information, choose "SED Tarda" as your search term in the Rare Disease Database.)
Mucolipidosis IV is a rare inherited metabolic disorder believed to be characterized by a deficiency of the enzyme ganglioside sialidase (neuraminidase). However, it has not been confirmed that this is the primary enzyme defect associated with this disorder. Mucolipidosis IV belongs to a group of diseases known as lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that break down certain fats and carbohydrates. A deficiency of ganglioside sialidase may lead to the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body. Mucolipidosis IV is characterized by mental retardation; severe impairment in the acquisition of skills requiring the coordination of muscular and mental activities (psychomotor retardation); diminished muscle tone (hypotonia); clouding (opacity) of the clear portion of the eyes through which light passes (cornea); and/or degeneration of the nerve-rich membrane lining the eyes (retinal degeneration). Mucolipidosis IV is thought to be inherited as an autosomal recessive trait. (For more information on this disorder, choose Òmucolipidosis IVÓ as your search term in the Rare Disease Database.)
Spondyloepimetaphyseal dysplasia, Strudwick type, is a rare genetic disorder characterized by short stature with abnormally short arms and legs (short-limbed dwarfism); incomplete closure of the roof of the mouth (cleft palate); abnormal inward curvature of the spine (lumbar lordosis); and/or the heel of the foot may be turned inward toward the body while the rest of the foot is bent downward and inward (talipes equinovarus or clubfoot). Abnormalities affecting the eyes may also occur including nearsightedness (myopia) and detachment of the nerve-rich membrane lining the eyes (retina). Spondyloepimetaphyseal dysplasia, Strudwick type is thought to be inherited as an autosomal dominant trait.
Treatment of congenital spondyloepiphyseal dyplasia includes early symptomatic correction of the clubfoot deformity, closure of the cleft palate, prevention of retinal detachment by regular ophthalmologic examinations and coagulation of early retinal tears. Ongoing orthopedic care is often necessary throughout life.
Genetic counseling will 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:
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For information about clinical trials sponsored by private sources, contact:
Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:358.
Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:220-23.
Gembun Y, et al. A case report of spondyloepiphyseal dysplasia congenita. J Nippon Med Sch. 2001;68:186-89.
Tiller GE, et al. Tandem duplication within a type II collagen gene (COPL2A1) exon in an individual with spondyloepiphyseal dysplasia. Proc Natl Acad Sci U S A. 1990;87:3889-93.
Anderson IJ, et al. Spondyloepiphyseal dysplasia congenital: genetic linkage to type II collagen (COL2AI). Am J Hum Genet. 1990;46:896-901.
Harrod MJ, et al. Genetic heterogeneity in spondyloepiphyseal dysplasia congenita. Am J Med Genet. 1984;8:311-20.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 183900; Last Update:4/12/00.
Report last updated: 2002/03/25 00:00:00 GMT+0