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Kniest Dysplasia

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Synonyms of Kniest Dysplasia

Disorder Subdivisions

General Discussion

Kniest dysplasia is one of several forms of dwarfism that is caused by a change (mutation) in a gene known as COL2A1. This gene is involved in the production of a particular protein that forms type 2 collagen, which is essential for the normal development of bones and other connective tissue. Changes in the composition of type 2 collagen lead to abnormal skeletal growth and, thus, to a variety of dwarfing conditions known as skeletal dysplasias.

Some of the signs and symptoms of Kniest dysplasia, such as short stature, enlarged knees, and cleft palate, are usually present at birth. Other characteristics may not appear for two or three years.


People with Kniest dysplasia are known to have an unusually short stature; short, deformed arms and legs; a chest that is "barrel-shaped" and abnormally short; and a relatively long trunk. Later in life, short trunk dwarfism develops due to curvature of the spine and enlargement of the joints.

People with Kniest dysplasia have an unusually flat face with protruding eyes, and a low nasal bridge. A cleft palate may also be present, and speech impairment may occur. Involvement of the eyes may include nearsightedness (myopia) that can progress to retinal detachment and cataracts. Dislocated eye lenses, drooping of the eyelids (blepharoptosis), possible blindness with disease of the optic nerve, involvement of the spine or brain, and glaucoma may also occur. As the person matures, the joints may become enlarged causing limited movement and pain. Limbs are short, often bowed, and there may be irregularities of the ends of the long bones (epiphyses). Contracted hips may cause walking difficulties and there may be a congenital flattening of the vertebrae and a hump of the spine. Affected individuals may sometimes exhibit hernias of the groin (inguinal) and navel (umbilical), frequent ear infections, slowed motor development and hearing loss.

Also characteristic of Kniest dysplasia are holes in the individual's cartilage, creating a "Swiss-cheese" appearance in cartilage that is significant for diagnostic purposes.

One variant of Kniest dysplasia that is extremely rare is known as Kniest-like dysplasia with pursed lips and ectopia lentis or Burton disease. It is characterized by a small mouth (microstomia) and pursed lips. In this variant, the collagen does not have the holes mentioned above.


Kniest dysplasia is the result of a change (mutation) in the gene known as COL2A1, which produces (codes for) the protein that forms collagen type 2. This gene has been mapped to the following gene map locus: 12q13.11-q13.20. The disorder is transmitted from parent to child as an autosomal dominant trait. In some instances, the mutation appears to be spontaneous, occurring for no apparent reason.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "12q13.11-q13.20" refers to a region between bands 13.11 and 13.20 on the long arm of chromosome 12. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is "turned off". A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.

X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.

Affected Populations

Kniest Syndrome is a rare disorder that affects males and females in equal numbers.

Related Disorders

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

Hypochondrogenesis (underdevelopment or lack of development of cartilage) is characterized by short-limb dwarfism, swelling of the body and face, widely spaced eyes (hypertelorism), a flat face and cleft palate. Respiratory distress may develop, due to the small rib cage, and is a significant concern. This disorder is an autosomal dominant trait. The mutation may be spontaneous in many cases.

Spondyloepiphyseal dysplasia congenita (SEDc) is characterized by short stature, clubfeet, and/or cleft palate. Other characteristics include a flat face, widely spaced eyes, barrel-shaped chest, and short neck, especially as the child grows older. The inheritance pattern is autosomal dominant.

Spondyloepimetaphyseal dysplasia (SEMD) is a disorder that resembles Morquio syndrome, as aggravated by curvature of the spine and a pigeon-breast. As in SEDc, cleft palate and retinal detachment are not uncommon.

Morquio syndrome is a metabolic disorder characterized by an accumulation of keratan sulfate. Bony abnormalities of the head, chest, hands, knees, and spine may occur as a result of this defect. Intelligence is usually normal. The bony abnormalities of the spine can result in spinal cord compression. Surgery to stabilize the upper cervical spine, usually by spinal fusion, can prevent severe paralysis. There may also be enlargement of the liver, curvature of the spine (thoracic kyphoscoliosis), a back flow of blood from the aortic valve of the heart into the left ventricle of the heart (aortic regurgitation), as well as loss of hearing. (For more information on this disorder, choose "Morquio" as your search term in the Rare Disease Database.)

Metatropic dwarfism, type I, is a rare genetic disorder characterized by extremely small stature, with short and deformed arms and legs. Other characteristics of this disorder are a narrow thorax with short ribs, prominent joints with restricted mobility of the knees and hips, and unusual increased extension of the finger joints. There is also an unusually long torso, which later develops into short trunk dwarfism due to curvature of the spine and enlargement of the joints. This rare disorder is often recognized at birth because the spinal deformities tend to be severe during infancy. (For information about other forms of dwarfism choose "Dwarfism" as your search term in the Rare Disease Database.)

Standard Therapies

Newborns with this disorder are clearly in distress so that x-rays may be ordered. Diagnosis may frequently be made on the basis of the radiographs developed, while a bone biopsy usually clarifies more ambiguous cases.

Treatment of Kniest syndrome usually consists of stabilization of lax joints, surgery to prevent contractures, and repair of retinal detachments and cleft palate. Genetic counseling may be of benefit for patients 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:

Kniest Dysplasia Resources



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Hall CM, Elcioglu NH. Metatropic dysplasia lethal variants. Pediatr Radiol. 2004;34:66-74.

Richards AJ, Morgan J, Bearcroft PW, et al. Vitreoretinopathy with phalangeal epiphyseal dysplasia, a type II collagenopathy resulting from a novel mutation in the C-propeptide region of the molecule. 2002;39:661-65.

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Weis MA, Wilkin DJ, Kim HJ, et al. Structurally abnormal type II collagen in a severe form of Kniest dysplasia caused by an exon skipping mutation. J Biol Chem. 1998;273:4761-68.

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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Kniest-Like Dysplasia with Pursed Lips and Ectopia Lentis. Entry Number; 245160: Last Edit Date; 12/29/1998.

Kniest Syndrome. International Birth Defects Information Systems (IBIS). ©2003. 4pp.

Type II Collagen Conditions. Greenberg Center for Skeletal Dysplasias. Updated 9/12/2002. 4pp.

Kniest Syndrome Group. Welcome to the KSG (Kniest SED Group) page for Spondyloepimetaphyseal Dysplasia (SMD) & Spondyloepiphyseal Dysplasia (SED) & Kniest. nd. 4pp.

Kniest Syndrome Group. Frequently asked questions about Kniest Dysplasia. nd. 4pp.

Kniest dysplasia. Orphanet. April 2004. 2pp.

Report last updated: 2008/04/11 00:00:00 GMT+0