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Disease Profile

Kuskokwim disease

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Arthrogryposis-like disorder; Kuskokwim syndrome; Arthrogryposis-like syndrome;


Congenital and Genetic Diseases


Kuskokwim disease is a congenital (present at birth) contracture disorder that occurs solely among Yup'ik Eskimos in and around the Kuskokwim River delta region of southwest Alaska. Affected individuals usually, but not always, have congenital contractures of large joints (especially knees and/or elbows) and spinal, pelvic, and foot deformities. Other skeletal features have also been reported. Kuskokwim disease has been shown to be caused by mutations in the FKBP10 gene and is inherited in an autosomal recessive manner.[1]


The range and and severity of signs and symptoms in individuals with Kuskokwim disease can vary, even among siblings. Affected individuals usually have congenital contractures, especially of lower extremities, which progress during childhood and persist for the lifetime of the individual. However, not all individuals with the condition have contractures at birth. The severity of contractures can be very asymmetrical in any given individual. The knees and elbows are often affected, and skeletal abnormalities of the spine, pelvis, and feet also commonly occur. Muscle atrophy of limbs with contractures and displacement of kneecaps (patellae) have also been reported.

Milder skeletal features are common. Vertebral features may include spondylolisthesis, mild to moderate scoliosis, and/or lordosis. Many affected individuals have had several low-energy fractures. Other skeletal abnormalities that have been reported include bunions (hallux valgus), "flat feet" (plano valgus feet), and clubfoot (talipes equinovarus). Development and arrangement of the teeth (dentition) are normal.

Although some individuals with full bilateral contractures of the knees can move about by “duck walking” (sitting with buttocks on their heels) or by “knee walking” (moving on their knees with their lower legs drawn up behind them to their buttocks), most affected individuals are treated with leg braces and/or surgery in childhood and can walk upright.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Aplasia/Hypoplasia of the patella
Absent/small kneecap
Absent/underdeveloped kneecap

[ more ]

Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

Joint stiffness
Stiff joint
Stiff joints

[ more ]

30%-79% of people have these symptoms
5%-29% of people have these symptoms
Abnormal clavicle morphology
Abnormal collarbone
Abnormal form of the vertebral bodies
Aplasia/Hypoplasia of the radius
Melanocytic nevus
Beauty mark
Reduced tendon reflexes
Percent of people who have these symptoms is not available through HPO
Ankle flexion contracture
Autosomal recessive inheritance
Coxa vara
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures

[ more ]

Hip contracture
Increased susceptibility to fractures
Abnormal susceptibility to fractures
Bone fragility
Frequent broken bones
Increased bone fragility
Increased tendency to fractures

[ more ]

Joint laxity
Joint instability
Lax joints

[ more ]

Knee flexion contracture
Hunched back
Round back

[ more ]

Pectus carinatum
Pigeon chest
Flattened vertebrae
Protrusio acetabuli
Short stature
Decreased body height
Small stature

[ more ]

Talipes equinovarus
Club feet
Club foot

[ more ]

Vertebral wedging
Wedge-shaped vertebrae


Treatment for Kuskokwim disease depends on the nature and severity of signs and symptoms in each affected individual. There is currently no completely successful approach to treat arthrogryposis. The goals of treatment may include lower-limb alignment, establishing stability for ambulation (moving about) and improving upper-limb function for self-care.[2] Many individuals with Kuskokwim disease are treated with leg braces and/or surgery and eventually are able to walk upright.[1]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Kuskokwim disease. Click on the link to view a sample search on this topic.


  1. Barnes AM et al. Kuskokwim Syndrome, a Recessive Congenital Contracture Disorder, Extends the Phenotype of FKBP10 Mutations. Hum Mutat. May 25, 2013; [Epub ahead of print]:
  2. Harold Chen. Arthrogryposis Treatment and Management. Medscape Reference. February 15, 2013; https://emedicine.medscape.com/article/941917-treatment. Accessed 8/8/2013.

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