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The Genetics of Kniest Dysplasia – COL2A1 Mutations and Collagen type II
Collagen is a protein component of skin, cartilage and bone, which is classified into three groups. The most abundant group is fibril-forming collagen which is further sub divided into types I to XXVII. Mutations in the various genes coding for these collagens give rise numerous disorders known collectively as the collagenopathies.
KND results from numerous different mutations in the COL2A1 gene, which codes for type II collagen. Most mutations reported to date are attributed to the phenomenon of exon skipping.
Histological examination of KND cartilage shows a characteristic pattern of chondrocytes within a highly vacuolated matrix which is often described by pathologists as 'Swiss cheese cartilage'. This abnormality of cartilage formation results in impaired skeletal development. Type II collagen is also important in the structure of the eye and ear, therefore ocular and aural pathology is also common in KND.
The condition is rare and is believed to have an autosomal, dominant pattern of inheritance i.e. only one copy of the mutated gene is necessary for the condition to manifest.
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Kniest Dysplasia Signs and Symptoms
There is no cognitive effects of kniest dysplasia. KND individuals show the same spectrum of intelligence seen in the general population. Common symptoms of KND include:
- Short torso and limbs - An alternative name for KND is metatropic dwarfism type II. Dwarfism may be apparent at birth, usually in the limbs rather than the torso. However in later years, shortening is more apparent in the torso. Final adult height ranges from 106-145 cm.
- Kyphoscoliosis – curvature of the spine
- Joint and mobility problems – some KND children may not walk until 3 years of age.
- Sight and hearing impairments – such as ottis media, hearing loss, myopia and retinal detachment.
- Breathing difficulties - usually as a result of a compressed torso.
- Psycho-social effects - Sadly, lack of understanding amongst the general population can sometimes cause KND individuals to feel marginalized or stigmatized. In particular children with KND can feel disadvantaged compared to their peers.
The severity of the condition varies greatly between individuals and therefore kniest dysplasia treatment should be individualized and symptomatic. Although the symptoms of KND can be severe, many with this condition lead active and fulfilled lives.
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Kniest Dysplasia Treatment
It is not possible to treat the underlying pathology of KND, but certain interventions can greatly improve quality of life.
- Joint replacement - premature cartilage degeneration is often seen in KND, making joint replacement necessary for KND individuals by the third or fourth decade of life.
- Interventions to monitor and treat visual impairments, hearing loss and osteoarthritis.
- Genetic counseling – since testing for collagen type II mutations is possible, genetic counseling can be useful for families affected by KND, especially when making reproductive choices.
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Support Groups and Associations
There are numerous organizations committed to improving the quality of life of those with short stature such as KND individuals. They can provide invaluable information and support for parents of KND children. They also bring people together for social events, so combating isolation:
- The Restricted Growth Association is a UK organization that aims to counteract stereotypes around dwarfism. They provide information and support to those affected by the condition.
- The Little People of America Group aims to educate the general public about dwarfism and actively campaigns on issues affecting people with short stature.
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Genetic and orthopedic aspects of collagen disorders. E.Carter. Current Opinion in Pediatrics, 2009, Vol 21, P46-54.
Kniest SED group website: ksginfo.org
Short statured people of Australia website: http://www.sspa.org.au