Kuskokwim disease is a very rare, inherited condition in which children are born with joint contractures—joints that are stiff and cannot fully straighten or bend. The knee and ankle joints are most commonly affected, and contractures can also involve feet, hips, elbows, and the spine. The condition has been reported almost exclusively in Yup’ik Alaska Native families living in and around the Kuskokwim River Delta of southwest Alaska. Intelligence is normal; the main problems are orthopedic (bones, joints, muscles). The disorder is present at birth or early childhood and tends to be lifelong, though supportive therapies can improve function. Global Genes+3MedlinePlus+3Orpha+3
Kuskokwim disease is a rare inherited condition that causes joint contractures. A contracture means a joint is stuck in a bent or stiff position and does not move normally. Most babies with this condition are born with contractures. The knees, ankles, and elbows are the most affected joints. The stiffness often gets worse during childhood. It then becomes stable and stays for life. Some people also have bone and spine changes and are shorter than others the same age. The condition has been found in a specific Alaska Native population (Yup’ik people) living around the Kuskokwim River Delta. MedlinePlus
Kuskokwim disease is caused by mutations in a gene called FKBP10, which makes a protein (FKBP65) that helps collagen mature correctly. Collagen is the “framework” protein that gives strength and flexibility to tendons, ligaments, bone, and other connective tissues. The founder mutation described in affected Yup’ik families deletes three DNA letters (c.877_879delTAC; p.Tyr293del), resulting in a very low amount of normal FKBP65 protein and abnormal collagen cross-linking, which contributes to contractures. PubMed+2PMC+2
Because FKBP65 is involved in collagen processing and cross-linking, the telopeptide lysines in collagen (critical “hooks” used to cross-link fibers) are poorly hydroxylated in Kuskokwim disease. This leads to reduced cross-linking and looser collagen fibrils in connective tissues, which helps explain the tight, contracted joints and related musculoskeletal findings. In lab studies of patient fibroblasts, telopeptide lysine hydroxylation was about 2–10% vs ~60% in controls. Ovid
The disease is caused by harmful changes (mutations) in a gene called FKBP10. This gene helps your body make a protein (FKBP65) that is needed for strong collagen. Collagen is the main support material in bones, joints, and many tissues. When FKBP10 does not work well, collagen “cross-linking” is weak and the support network is disorganized. This likely explains why joints become stiff and bones can have shape changes. The condition is passed in an autosomal recessive pattern, which means a child must inherit two changed copies of FKBP10 (one from each parent). MedlinePlus
A historic medical report from 1969 described this disorder in Yup’ik families and noted multiple joint contractures, normal thinking ability, and no consistent problems outside the skeleton. Electromyography (EMG) and muscle biopsies were reported as normal, and treatment focused on orthopedic care such as bracing, casting, and surgery. JAMA Network
Later genetic studies confirmed that FKBP10 mutations can cause the Kuskokwim form of congenital contractures, and that FKBP10 changes can also cause related conditions such as Bruck syndrome and some forms of osteogenesis imperfecta. This shows there is a spectrum of problems linked to the same collagen-processing pathway. MedlinePlus+2PMC+2
Other names
Doctors and genetic resources use several names for this condition:
Kuskokwim disease
Kuskokwim syndrome
Arthrogryposis-like syndrome (because it resembles arthrogryposis with multiple congenital contractures)
Bruck syndrome 1 (the FKBP10-related form within the Bruck syndrome spectrum)
All of these refer to the same core disorder in this context. MedlinePlus+1
Types
There is no official “type 1, type 2, type 3” breakdown inside Kuskokwim disease itself. Instead, doctors think of a clinical spectrum:
Milder end: contractures mainly in the knees or ankles, with smaller effects on height and spine. MedlinePlus
Typical: contractures of knees, ankles, and elbows that start at birth, worsen through childhood, then stabilize; some spine, pelvis, or foot changes may appear. MedlinePlus
Severe end: broader, earlier contractures and more obvious skeletal findings (for example, scoliosis or lordosis), still with normal intelligence. Historic reports emphasized orthopedics as the main care. JAMA Network
Doctors also discuss related conditions in the same pathway, such as Bruck syndrome and recessive osteogenesis imperfecta due to FKBP10, to understand overlap and differences. MedlinePlus+1
Causes
Strictly speaking, Kuskokwim disease has one root cause: pathogenic variants in the FKBP10 gene that disrupt collagen cross-linking. Below are 20 plain-language “causal factors” or mechanisms and contributors that together explain why the disease appears, varies, and persists in families and communities. Each item ties back to the same core FKBP10 pathway.
Biallelic FKBP10 mutations: a child inherits one nonworking FKBP10 copy from each parent. This is the direct cause. MedlinePlus
Loss of FKBP65 protein function: the FKBP10 protein becomes unstable and breaks down, leaving very low levels in cells. MedlinePlus
Weak collagen cross-linking: collagen fibers lack strong links, so tissues that need toughness (bones, joints, tendons) are compromised. MedlinePlus
Disorganized extracellular matrix: collagen networks are laid down in a less orderly way, affecting joint shape and movement. MedlinePlus
Autosomal recessive inheritance: the inheritance pattern concentrates disease in families where both parents carry a variant. MedlinePlus
Founder effect: in small or isolated populations, a once-rare FKBP10 change can become more common over generations. (This principle helps explain clustering in the Yup’ik population.) MedlinePlus+1
Genetic drift in small communities: random changes in gene frequencies can increase carrier rates. (General population genetics context for the observed geographic clustering.) JAMA Network
Modifier genes: other genes may fine-tune the severity of contractures by affecting collagen processing or bone growth, which explains variation between people with the same FKBP10 change. (Supported by variability across the FKBP10 spectrum.) Oxford Academic
Prenatal joint positioning: with weaker connective tissue support, fetal joint movement may be reduced, leading to fixed positions at birth. (Mechanistic inference consistent with congenital contracture disorders.) JAMA Network
Tendon and ligament stiffness: abnormal collagen in these tissues can limit joint range from early life. MedlinePlus
Bone shape changes: altered growth at the spine, pelvis, and feet can lock joints into less flexible positions. MedlinePlus
Muscle imbalance around joints: long-standing contractures can cause certain muscles to tighten and others to weaken, maintaining stiffness. (Described in classic reports of contracture patterns.) JAMA Network
Progression during childhood: growing bones and tissues respond to abnormal collagen by worsening angles and curves before stabilizing. MedlinePlus
Limited remodeling capacity: once collagen is laid down abnormally, joints may not remodel enough to restore normal motion. MedlinePlus
Mechanical loading: walking and weight bearing on misaligned joints can reinforce stiffness over time. (General orthopedic principle applied to this condition.) JAMA Network
Scar-like collagen: disorganized collagen can behave like stiffness-producing scar tissue around joints. MedlinePlus
Scoliosis and lordosis: spine curves change body mechanics and can limit hip and knee range. MedlinePlus
Foot deformities: bunions, flat feet, or clubfoot change gait and joint use, promoting further contractures. YK Health
Community carrier frequency: when more people carry the same variant, two carriers are more likely to have an affected child. (Population genetics explanation for clustering.) MedlinePlus+1
Spectrum of FKBP10-related disease: overlap with Bruck syndrome and osteogenesis imperfecta shows that the same pathway can present mainly with contractures in this community, reinforcing FKBP10 as the unifying cause. MedlinePlus+1
Symptoms and common clinical features
Stiff joints (contractures) at birth, especially knees, ankles, and elbows. This is the hallmark feature. MedlinePlus
Contractures that worsen in childhood and then stabilize. Families often notice progression before school years. MedlinePlus
Limited range of motion: difficulty fully straightening or bending affected joints. MedlinePlus
Shorter height than peers, often noticed in later childhood. MedlinePlus
Spine changes like lordosis (inward lower-back curve) or scoliosis (side-to-side curve). MedlinePlus
Wedge-shaped vertebrae seen on X-rays, which can link to spinal curves. MedlinePlus
Pelvis shape differences, which may affect hip movement and walking. MedlinePlus
Foot deformities (bunions, flat feet, or clubfoot), which may change balance and gait. YK Health
Macrocephaly (large head size) in some people; brain function is normal. MedlinePlus
Normal intelligence and no consistent problems outside the skeleton and sometimes skin, per the classic report. JAMA Network
Gait differences: walking may be slower or use braces due to knee/ankle angles. YK Health
Muscle imbalance around stiff joints (some groups tight, others weak), contributing to posture issues. JAMA Network
Functional limits in activities that need full joint flexion or extension (for example, squatting, running). MedlinePlus
Progressive orthopedic needs in childhood (braces, therapy), often fewer changes in adulthood after stabilization. JAMA Network+1
Family history consistent with recessive inheritance (affected siblings with healthy parents who are carriers). MedlinePlus
Diagnostic tests
A) Physical examination
General joint exam: a doctor inspects joint posture and looks for fixed positions typical of contractures. This confirms the pattern and distribution. MedlinePlus
Range-of-motion measurement (goniometry): measures how far each joint moves; important for tracking changes over time. JAMA Network
Spine assessment: checks for scoliosis and lordosis and any back pain or breathing limits related to spinal curves. MedlinePlus
Gait and function evaluation: watches walking, balance, and daily activities to guide therapy and bracing. YK Health
Growth and body proportions: height, head size, and limb proportions are recorded to document short stature and macrocephaly patterns. MedlinePlus
B) Manual/bedside tests
Contracture stretch testing (gentle, supervised): shows real-world stiffness and helps set therapy goals. JAMA Network
Functional scales (for example, timed walking tests): track how contractures affect movement over time. YK Health
Orthotic fitting assessment: determines brace type (ankle-foot orthoses or knee devices) to improve alignment and mobility. YK Health
Posture and alignment checks: simple plumb-line or wall tests can reveal trunk balance issues from spine curves. MedlinePlus
Skin inspection over joints: looks for pressure areas from bracing or altered joint angles; skin findings were occasionally noted historically. JAMA Network
C) Laboratory and pathological tests
Genetic testing for FKBP10: the key confirmatory test. Finding two pathogenic variants proves the diagnosis and guides family counseling. YK Health
Targeted family testing (carrier testing): identifies relatives who carry one FKBP10 change so families can make informed reproductive choices. MedlinePlus
Collagen biochemistry (specialized centers): research-level assays show reduced collagen cross-linking when FKBP10 is defective. MedlinePlus
Rule-out tests for other arthrogryposis causes (when genetics is unclear): used to exclude neuromuscular, metabolic, or connective-tissue disorders with different causes. Historic studies in Kuskokwim cases showed otherwise normal routine labs. JAMA Network
Prenatal or preimplantation genetic testing (in families with known variants): optional testing to detect FKBP10 changes before or during pregnancy. MedlinePlus
D) Electrodiagnostic tests
Electromyography (EMG): historic reports found no basic motor-unit abnormality in Kuskokwim disease. A normal EMG helps separate it from primary nerve or muscle disease. JAMA Network
Nerve conduction studies: typically normal; used when the clinical picture is unclear to exclude neuropathies. JAMA Network
E) Imaging tests
Plain X-rays of the spine and pelvis: look for wedge-shaped vertebrae, scoliosis, lordosis, and pelvic changes that guide bracing or surgery decisions. MedlinePlus
Foot and lower-limb X-rays: assess bunions, flat feet, or clubfoot, and the angles at the knee and ankle that maintain contractures. YK Health
Periodic imaging follow-up in growing children: monitors curve progression or joint angles during the phase when contractures tend to worsen, so care can be timed well. MedlinePlus
Non-pharmacological treatments
Early, gentle stretching program
Daily therapist-guided and home stretching keeps joints moving and slows tightening. Purpose: preserve range of motion (ROM) and delay contracture progression. Mechanism: low-load, long-duration stretch lengthens muscle-tendon units and remodels connective tissue over time. OrphaPhysiotherapy-led ROM and strengthening
Regular PT improves joint mobility and strengthens supporting muscles to aid walking and transfers. Mechanism: graded exercise promotes neuromuscular control and joint stability, reducing secondary pain from abnormal mechanics. OrphaSerial casting for clubfoot/ankle equinus
Short-term weekly casts gradually reposition the foot toward neutral. Purpose: correct deformity without surgery when possible. Mechanism: progressive stretch of soft tissues. OrphaNight splints or dynamic splints
Custom braces hold joints at comfortable end-range during sleep to maintain gains from therapy. Mechanism: prolonged, gentle stretch encourages tissue remodeling. OrphaAnkle-foot orthoses (AFOs) and custom footwear
Orthoses improve ankle alignment, balance, and foot clearance; shoes accommodate deformities and reduce falls. Mechanism: external support redistributes forces and improves gait efficiency. OrphaOccupational therapy (ADL training)
OT teaches strategies and adaptive tools for dressing, bathing, and school tasks, boosting independence. Mechanism: task-specific training and assistive devices reduce strain on stiff joints. OrphaGait training and balance work
Practice with parallel bars, canes, or walkers refines safe ambulation and reduces fall risk. Mechanism: motor learning and proprioceptive feedback. OrphaHydrotherapy (water-based exercise)
Therapy in warm water enables low-impact movement with buoyancy support, easing stiffness and pain. Mechanism: reduced joint loading and gentle resistive properties of water. OrphaPostural and spine care
Programs to maintain neutral spine and hip alignment limit compensatory deformities. Mechanism: muscle balance and ergonomic positioning reduce focal overload. OrphaContracture-prevention education for families
Coaching on home programs, splint use, and early signs of worsening helps maintain progress. Mechanism: consistent daily routines sustain tissue length. OrphaSchool-based accommodations
Seating, extra time for transitions, and accessible PE maintain participation and reduce fatigue. Mechanism: environmental changes reduce musculoskeletal stress. OrphaPain self-management (heat/cold, pacing)
Localized heat before stretch and ice after activity can ease symptoms; pacing prevents flares. Mechanism: thermal modulation of nociceptors and inflammation. OrphaManual therapy (soft-tissue mobilization)
Gentle mobilization around contracted tissues may reduce myofascial restriction. Mechanism: viscoelastic tissue creep and improved glide of fascia. OrphaBreathing, relaxation, and biofeedback
Useful for coping with chronic symptoms and therapy intensity. Mechanism: autonomic down-regulation reduces muscle guarding and perceived pain. OrphaNutritional support for musculoskeletal health
Balanced protein, calcium, vitamin D are important for growth and rehab participation. Mechanism: supports bone and soft-tissue turnover. OrphaFall-prevention home modifications
Lighting, clutter reduction, and railings reduce injury risk in those with gait limits. Mechanism: hazard control. OrphaCommunity-based mobility aids
Wheelchairs or scooters for distances can preserve energy for school or work. Mechanism: energy conservation while maintaining participation. OrphaRegular orthopedic follow-up
Monitoring detects progressive deformities early and times interventions optimally. Mechanism: surveillance and timely correction. OrphaPsychosocial support and peer groups
Helps families manage the stress of a rare, lifelong condition. Mechanism: coping skills and adherence support. OrphaGenetic counseling for families
Explains inheritance, carrier testing, and options for future pregnancies in an autosomal recessive disorder. Mechanism: informed decision-making. MedlinePlus
Drug treatments
Important: There are no disease-modifying drugs for Kuskokwim disease; medicine use is supportive (e.g., pain control around therapy or surgery). Doses below are common references for otherwise healthy adults unless noted. Children require weight-based dosing; always prescribe with a clinician. Orpha
Acetaminophen (Paracetamol) – analgesic/antipyretic
Class: Non-opioid analgesic. Typical adult dose: 500–1,000 mg every 6–8 h (max 3,000–4,000 mg/day depending on local guidance). Purpose: baseline pain relief to tolerate therapy and splinting. Mechanism: central COX modulation; Side effects: generally safe at correct dose; hepatotoxicity if overdose or with heavy alcohol use. OrphaIbuprofen – NSAID
Class: NSAID. Adult dose: 200–400 mg every 6–8 h with food (max 1,200 mg OTC; higher by prescription). Purpose: short-term pain/inflammation around intensive therapy or after minor procedures. Risks: GI upset/bleeding, kidney effects. OrphaNaproxen – NSAID
Class: NSAID. Adult dose: 250–500 mg twice daily with food. Purpose: longer-acting option for musculoskeletal pain. Risks: GI and renal adverse effects; avoid in certain heart disease. OrphaTopical NSAIDs (e.g., diclofenac gel)
Class: Topical NSAID. Dose: apply per label to painful area up to 4×/day. Purpose: focal pain with lower systemic risk. Risks: local skin irritation. OrphaShort course oral NSAID rotation
Class: NSAID strategy. Using minimal-effective dose for brief periods around flares or casting changes. Purpose: symptom spikes. Risks: same as NSAIDs; use gastroprotection if needed. OrphaAcetaminophen + NSAID alternating plan
Class: Analgesic combination. Purpose: better pain control without escalating doses of either. Mechanism: additive analgesia via central + peripheral pathways. Risks: cumulative dosing oversight—use written schedule. OrphaShort course opioids (post-op only)
Class: Opioid analgesics (e.g., oxycodone). Dose: lowest effective dose for a few days after major orthopedic surgery. Purpose: acute post-surgical pain. Risks: sedation, constipation, dependence—avoid routine use. OrphaPeri-operative regional anesthesia/nerve blocks
Class: Local anesthetics (procedural). Dose: by anesthesiologist. Purpose: improve pain control and early mobilization after orthopedic procedures. Risks: rare nerve injury, local anesthetic toxicity. OrphaMuscle relaxants (e.g., short-term cyclobenzaprine)
Class: Centrally acting muscle relaxant. Purpose: treat reactive muscle spasm around painful joints; not for fixed contracture. Risks: drowsiness; avoid chronic use. OrphaGabapentin (if neuropathic-type pain features)
Class: Anticonvulsant/neuropathic analgesic. Dose: titrate from 100–300 mg at night. Purpose: burning/tingling pain if present (not typical). Risks: dizziness, somnolence. OrphaTopical lidocaine patches
Class: Local anesthetic. Dose: up to 12 h on/12 h off over focal pain. Purpose: localized pain control aiding therapy. Risks: skin irritation. OrphaProton-pump inhibitor (with high-risk NSAID use)
Class: Gastroprotection (e.g., omeprazole 20 mg daily). Purpose: reduce ulcer risk if NSAIDs are necessary in at-risk patients. Risks: headache, rare nutrient effects with long use. OrphaAcetaminophen-codeine (limited use)
Class: Combination analgesic. Purpose: second-line short-term post-op option when NSAIDs contraindicated. Risks: constipation, sedation, codeine variability. OrphaNSAID plus physical-therapy timing
Class: Analgesic scheduling. Give dose 30–60 min before therapy to improve participation, then taper as function improves. Risks: as per NSAID. OrphaVitamin D (correct deficiency)
Class: Nutrient therapy. Dose: per lab-guided replacement. Purpose: support bone health in individuals with altered mechanics; not disease-modifying. Risks: hypercalcemia if overdosed. OrphaCalcium (dietary or supplement if low intake)
Class: Mineral. Dose: as per age/sex recommendations. Purpose: skeletal support; adjunct to rehab. Risks: kidney stones in excess. OrphaAcetaminophen-only protocol in NSAID-intolerant
Class: Analgesic strategy. Purpose: safe pain plan when NSAIDs are contraindicated. Risks: hepatotoxicity if dosing errors. OrphaShort peri-operative antibiotics (surgical prophylaxis only)
Class: Antibiotics. Purpose: standard infection prevention in orthopedic surgery; not a disease treatment. Risks: allergy, resistance. OrphaLocal corticosteroid injection (select tendinopathies)
Class: Glucocorticoid (local). Purpose: treat specific overuse tendinopathy from altered biomechanics; not for fixed contracture. Risks: tendon weakening if repeated. OrphaMultimodal post-op analgesia pathway
Class: Protocol combining acetaminophen, NSAID (if safe), nerve block, and limited opioid. Purpose: better pain control and earlier mobilization. Risks: medication-specific. Orpha
Why so conservative? In Kuskokwim disease, contractures are structural, not caused by muscle spasticity or inflammation alone, so drugs only support therapy and surgery—they don’t reverse the fixed deformity. Orpha
Dietary molecular supplements
Always check with clinicians, especially for children and peri-operative periods. Evidence here supports general musculoskeletal health, not disease reversal. Orpha
Vitamin D – supports bone and muscle function; dose guided by blood levels to reach sufficiency. Mechanism: calcium-phosphate balance and muscle performance. Orpha
Calcium – meet age-appropriate intake via diet first; supplement if needed. Mechanism: bone mineralization. Orpha
Protein adequacy (whey/casein if intake is low) – supports muscle repair after therapy. Mechanism: amino acids for tissue remodeling. Orpha
Omega-3 fatty acids – modest analgesic/anti-inflammatory effect for activity-related pain. Mechanism: eicosanoid modulation. Orpha
Magnesium (if deficient) – supports muscle relaxation and energy metabolism. Mechanism: cofactor in ATP-dependent processes. Orpha
Vitamin C – cofactor in collagen synthesis; target normal dietary intake. Mechanism: prolyl/lysyl hydroxylase support. Orpha
Collagen peptides – may support tendon/ligament recovery with PT; evidence generalizable from sports tendon data, not specific to KS. Mechanism: provides peptide building blocks. Orpha
B-complex (if dietary insufficiency) – supports energy for rehabilitation. Mechanism: coenzymes in metabolism. Orpha
Zinc (if deficient) – tissue repair cofactor; avoid excess. Mechanism: enzyme function in protein synthesis. Orpha
Iron (only if iron-deficient) – improves exercise tolerance when anemia is present. Mechanism: oxygen transport. Orpha
Immunity-booster / regenerative / stem-cell” drugs
There are no validated immune “boosters” or stem-cell drugs for Kuskokwim disease. Here’s what can appropriately be discussed in clinical contexts: Orpha
Standard childhood vaccinations (schedule-based) – protect overall health so children can safely participate in therapy and surgery; not disease-specific, but essential. Mechanism: adaptive immunity to prevent infections that could delay rehab. Orpha
Vitamin D repletion (as needed) – supports immunity broadly and bone/muscle health; dose by labs. Mechanism: immune modulation and musculoskeletal support. Orpha
Peri-operative antibiotic prophylaxis (procedure-specific) – given around surgery to prevent infection; not an “immunity booster.” Mechanism: lowers bacterial load at incision. Orpha
Investigational regenerative approaches – At present, no clinical trials show benefit of stem-cell or gene therapy for Kuskokwim disease; any such therapy would be experimental and should only occur in ethics-approved research. Mechanism proposed would target collagen processing, but this does not exist clinically now. Orpha
Good nutrition + sleep – foundational for immune function and tissue recovery after therapy or surgery. Mechanism: supports cytokine balance and anabolic processes. Orpha
Infection prevention (vaccines/hand hygiene) – practical measures that keep therapy on track. Mechanism: reduce illness-related setbacks. Orpha
Surgeries
Soft-tissue release (tenotomy/capsulotomy) – Surgeons lengthen tight tendons or release contracted joint capsules to improve range of motion in severely restricted joints. Done when therapy and splinting cannot achieve functional alignment. Orpha
Foot deformity correction (e.g., clubfoot surgery or tendon transfers) – Corrects rigid foot positions to allow plantigrade (flat) standing/walking and pain reduction. Considered when serial casting/orthoses fail. Orpha
Osteotomy (bone realignment) – Re-angles bones around a deformed joint to improve mechanics and weight-bearing. Used for persistent malalignment of tibia/foot or patellar issues. Orpha
Patellar realignment procedures – Addresses displaced or unstable kneecap to improve tracking, stability, and reduce pain. Selected patients only. Global Genes
Spine or pelvic procedures (select cases) – Corrects significant deformity affecting mobility or seating tolerance. Reserved for severe, function-limiting cases after team evaluation. Orpha
Preventions
Because Kuskokwim disease is genetic, we cannot prevent the condition itself with lifestyle steps, but we can prevent secondary problems: regular stretching, consistent splint/orthosis use, safe activity pacing, fall-proof home setup, timely orthopedic check-ups, adequate nutrition (protein, vitamin D, calcium), good footwear, school/work accommodations, vaccination to reduce illness-related rehab gaps, and genetic counseling for family planning. MedlinePlus+1
When to see doctors
See your healthcare team promptly for: worsening stiffness or new contractures, frequent falls, painful or red/swollen joints, skin breakdown under braces/casts, foot deformity that prevents shoe wear, sudden gait regression, signs of infection (fever, wound drainage) after procedures, or concerns about growth and participation at school. Regular scheduled visits with rehabilitation, orthopedics, and genetics are recommended even when stable. Orpha
What to eat and what to avoid
Eat: balanced meals with adequate protein (growth/repair), calcium and vitamin D (bones), fruits/vegetables (micronutrients), and enough calories to support therapy. Avoid/limit: ultra-processed foods low in nutrients, excess sugary drinks, excess salt, and supplement megadoses that can harm (e.g., too much vitamin D or calcium). Hydration before therapy helps performance. Nutrition supports health but does not cure contractures. Orpha
Frequently asked questions
Is Kuskokwim disease the same as arthrogryposis?
It’s an arthrogryposis-like condition with a specific genetic cause (FKBP10) in Yup’ik families; it overlaps but is distinct from other arthrogryposes. Rare Diseases +1What gene is involved?
FKBP10, producing protein FKBP65 that helps collagen mature; the p.Tyr293del founder variant is reported in affected families. OvidWhy do joints get stiff?
Abnormal collagen cross-linking causes tight connective tissues and fixed joint positions (contractures). OvidDoes it affect learning or thinking?
No consistent cognitive problems have been reported; issues are mainly musculoskeletal. JAMA NetworkHow is it diagnosed?
Clinical exam plus genetic testing for FKBP10 confirms the diagnosis. Imaging helps plan treatment. MedlinePlus+1Can medicine cure it?
No. Medicines help with pain and therapy participation; structural contractures need therapy, orthoses, casting, and sometimes surgery. OrphaAre there experimental gene or stem-cell treatments?
Not clinically available or proven for Kuskokwim disease as of now. Participation should only be in approved research if trials appear. OrphaWill my child walk?
Many children can walk, sometimes with orthoses or after foot correction; others may use mobility aids for distances. Individual outcomes vary. OrphaDoes it get worse over time?
Contractures are generally lifelong; with good rehab and orthopedics, function can be maintained and complications reduced. OrphaIs it only in Alaska?
It has been reported almost exclusively in Yup’ik communities of the Kuskokwim River Delta. MedlinePlusWhat is the inheritance risk?
Autosomal recessive: if both parents are carriers, each child has a 25% chance of being affected. Genetic counseling is advised. MedlinePlusWhat specialists do we need?
Rehabilitation medicine/physiotherapy, orthopedics, genetics, OT, and sometimes podiatry and pain management. OrphaCould FKBP10 mutations cause other diseases?
Yes—other FKBP10 variants can cause osteogenesis imperfecta and Bruck syndrome; Kuskokwim disease represents a specific phenotype. PubMedAre there community resources?
Rare-disease resources (e.g., Orphanet, GARD) and regional Alaska Native health systems offer information and coordinated care. Orpha+1Where can I read more?
MedlinePlus Genetics, Orphanet, GARD, and the original research by Barnes et al. (2013) in Human Mutation provide detailed overviews and molecular findings. PubMed+3MedlinePlus+3Orpha+3
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: September 23, 2025.
