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Pseudoachondroplastic Dysplasia

Synonyms of Pseudoachondroplastic Dysplasia

  • No synonyms found.

Disorder Subdivisions

  • No subdivisions found.

General Discussion

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 abnormally increased curvature of the bones of the lower spine (lumbar lordosis) and front-to-back curvature of the spine (kyphosis). Cases of pseudoachondroplastic dysplasia are due to mutations of the COMP gene. Most cases of pseudoachondroplastic dysplasia are inherited as an autosomal dominant trait. However, a recessive form of the disorder may also exist.

Symptoms

The symptoms associated with pseudoachondroplastic dysplasia vary from case to case. Researchers have proposed that different forms of the disorder exist, distinguished by inheritance pattern and severity.

Affected infants may exhibit growth deficiency during the first few years of life, resulting in short stature. In most cases, the arms and legs may be abnormally short and the fingers may be abnormally short and stubby (brachdactyly). There may be delays in affected infants learning to walk. When affected infants begin to walk, they may exhibit a characteristic manner of walking (waddling gait).

As affected infants age, they may exhibit abnormal looseness (hypermobility) of certain joints, resulting in abnormally bowed legs (genu varum), knees that are bent backward (genu recurvatum), and/or a malformation in which the knees are abnormally close together and the ankles are unusually far apart (genu valgum). In some cases, the wrist may be abnormally flexed toward the pinky side of the hand (ulnar deviation of the wrist) and the elbows and hips may have limited flexibility.

In addition, affected individuals may have side-to-side curvature of the spine (scoliosis), increased curvature of the bones of the lower spine (lumbar lordosis), and/or front-to-back curvature of the spine (kyphosis).

Abnormalities affecting the long bones of the arms and legs may result in progressive degeneration, stiffness, tenderness, and pain of the joints (osteoarthritis) during early adulthood.

Causes

Most cases of pseudoachondroplastic dysplasia occur randomly as the result of a spontaneous genetic change (i.e., new mutation). The mutation 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.

Some researchers believe that recessively inherited forms of the disorder exist. In recessive disorders, the condition does not occur unless an individual inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Some cases of pseudoachondroplastic dysplasia may be caused by genetic disruptions or changes (mutations) to the cartilage oligomeric matrix protein (COMP) gene located on the short arm (p) of chromosome 19 (19p13.1). 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, "chromosome 19p13.1" refers to band 13.1 on the short arm of chromosome 19.

Affected Populations

Pseudoachondroplastic dysplasia affects males and females in equal numbers. The exact prevalence of this disorder in the general population is unknown.

Originally, researchers suspected that four types of pseudoachondroplastic dysplasia existed. The four types were differentiated by severity and inheritance. (Two were dominant traits and two were recessive traits). These disorders were designated pseudoachondroplastic dysplasia types I-IV. Type III is the most common form of pseudoachondroplastic dysplasia and is inherited as an autosomal dominant trait. Type IV is now believed to be a recessively inherited, severe form of type III. Types I and II have yet to be well established or characterized in the medical literature.

Related Disorders

Symptoms of the following disorders can be similar to those of pseudoachondroplastic dysplasia. Comparisons may be useful for a differential diagnosis:

Multiple epiphyseal dysplasia (MED) is a rare inherited spectrum of disorders characterized by malformation (dysplasia) of the "growing portion" or head of the long bones (epiphyses). Affected individuals may have an abnormally short thighbone (femur), unusually short hands and fingers, mild short stature, a waddling gait, and/or pain in the hips and knees. In some cases, painful swelling and inflammation of certain joints (arthritis) may be present as early as five years of age. Most cases of multiple epiphyseal dysplasia are inherited as autosomal dominant traits; rare cases are inherited as autosomal recessive traits. Some cases of multiple epiphyseal dysplasia are due to mutations of the COMP gene, meaning that those cases are allelic to some cases of multiple epiphyseal dysplasia (i.e., caused by different mutations of the same disease gene). (For more information on this disorder, choose "multiple epiphyseal dysplasia" as your search term in the Rare Disease Database.)

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. (For more information on this disorder, choose "congenital spondyloepiphyseal dysplasia " as your search term in the Rare Disease Database.)

Achondroplasia is a rare genetic disorder characterized by distinctive abnormalities of the head and facial (craniofacial) area; unusually short upper arms and legs and short stature (short-limbed dwarfism); and short hands with fingers that assume a "trident" or three-pronged position during extension. Affected individuals may also have limited extension of the elbows and hips, bowing of the legs, and abnormally increased curvature of the bones of the lower spine (lumbar lordosis). In addition, many individuals with achondroplasia have an abnormally enlarged brain (macrencephaly), a prominent forehead (frontal bossing), and a flat (depressed) nasal bridge. In some cases, affected individuals may experience inhibition of the normal flow of cerebrospinal fluid (CSF), potentially causing increased pressure on brain tissue. In most cases, achondroplasia appears to occur randomly (sporadically) due to new genetic changes (mutations). In other cases, the disorder may be inherited as an autosomal dominant trait. (For more information on this disorder, choose "Achondroplasia" as your search term in the Rare Disease Database.)

Hypochondroplasia is a rare inherited skeletal disorder characterized by short stature with abnormally short arms and legs (short-limbed dwarfism). Major symptoms may include bowing of the legs, abnormally short fingers and toes (brachydactyly), mild limitation of elbow motions, and/or abnormal backward curvature (lordosis) of the spine. In addition, affected children may have abnormalities of the head and face (craniofacial) area including drooping of the upper eyelids (ptosis), an abnormally prominent forehead (frontal bossing), and/or an unusually large head (macrocephaly). Hypochondroplasia is thought to be inherited as an autosomal dominant trait. (For more information on this disorder, choose "Hypochondroplasia" as your search term in the Rare Disease Database.)

Standard Therapies

Treatment
The treatment of pseudoachondroplastic dysplasia is directed toward the specific symptoms that are apparent in each individual. Surgical correction of skeletal abnormalities may be necessary. Hip replacement surgery may be necessary in some adults with pseudoachondroplastic dysplasia.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

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: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to Pseudoachondroplastic Dysplasia

Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., short stature, skeletal abnormalities, etc.)

References

TEXTBOOKS
Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:422-23.

Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:354.

Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1971.

JOURNAL ARTICLES
Wirtz DC, et al. Bilateral total hip replacement in pseudoachondroplasia. Acta Orthop Belg. 2000;66:405-08.

Deere M, et al. Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia. Am J Med Genet. 1999;85:486-90.

Ikegawa S, et al. Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Genet. 1998;103:633-38.

Ikegawa S, et al. Pseudoachondroplasia with de novo deletion [del(11)(q21q22.2)]. Am J Med Genet. 1998;77:356-59.

Briggs MD, et al. Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum. Am J Med Genet. 1998;62:311-19.

McKeand J, et al. Natural history study of pseudoachondroplasia. Am J Med Genet. 1996:63:606-10.

Hecht JT, et al. Linkage of typical pseudoachondroplasia to chromosome 19. Genomics. 1993;18:661-66.

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Report last updated: 2008/04/22 00:00:00 GMT+0

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