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Reviewed November 2013
What is Kuskokwim syndrome?
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).
How common is Kuskokwim syndrome?
Kuskokwim syndrome is extremely rare. It affects a small number of people from the Yup'ik Eskimo population in southwest Alaska.
What genes are related to Kuskokwim syndrome?
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.
Read more about the FKBP10 gene.
How do people inherit 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.
Where can I find information about diagnosis or management of Kuskokwim syndrome?
These resources address the diagnosis or management of Kuskokwim syndrome and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about Kuskokwim syndrome?
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.
What other names do people use for Kuskokwim syndrome?
What if I still have specific questions about Kuskokwim syndrome?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding Kuskokwim syndrome?
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.
See also Understanding Medical Terminology.
References (3 links)
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? in the Handbook.