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Kuskokwim syndrome is characterized by joint deformities called contractures that restrict the movement of affected joints. This condition has been found only in a population of native Alaskans known as Yup'ik Eskimos, who live in and around a region of southwest Alaska known as the Kuskokwim River Delta.
In Kuskokwim syndrome, contractures most commonly affect the knees, ankles, and elbows, although other joints, particularly of the lower body, can be affected. The contractures are usually present at birth and worsen during childhood. They tend to stabilize after childhood, and they remain throughout life.
Some individuals with this condition have other bone abnormalities, most commonly affecting the spine, pelvis, and feet. Affected individuals can develop an inward curve of the lower back (lordosis), a spine that curves to the side (scoliosis), wedge-shaped spinal bones, or an abnormality of the collarbones (clavicles) described as clubbing. Affected individuals are typically shorter than their peers and they may have an abnormally large head (macrocephaly).
Kuskokwim syndrome is extremely rare. It affects a small number of people from the Yup'ik Eskimo population in southwest Alaska.
Kuskokwim syndrome is caused by mutations in the FKBP10 gene, which provides instructions for making the FKBP65 protein. This protein is important for the correct processing of complex molecules called collagens, which provide structure and strength to connective tissues that support the body's bones, joints, and organs. Collagen molecules are cross-linked to one another to form long, thin fibrils, which are found in the spaces around cells (the extracellular matrix). The formation of cross-links results in very strong collagen fibrils. The FKBP65 protein attaches to collagens and plays a role in their cross-linking.
A mutation in the FKBP10 gene alters the FKBP65 protein, making it unstable and easily broken down. As a result, people with Kuskokwim syndrome have only about 5 percent of the normal amount of FKBP65 protein. This reduction in protein levels impairs collagen cross-linking and leads to a disorganized network of collagen molecules. It is unclear how these changes in the collagen matrix are involved in the development of joint contractures and other abnormalities in people with Kuskokwim syndrome.
Changes in this gene are associated with Kuskokwim syndrome.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of Kuskokwim syndrome and may include treatment providers.
You might also find information on the diagnosis or management of Kuskokwim syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/kuskokwim-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/kuskokwim-syndrome/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about Kuskokwim syndrome helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
arthrogryposis ; autosomal ; autosomal recessive ; cell ; collagen ; extracellular ; extracellular matrix ; gene ; inherited ; joint ; lordosis ; macrocephaly ; mutation ; pelvis ; population ; protein ; recessive ; scoliosis ; syndrome
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.