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Arthrogryposis

  1. Disease/Disorder:
    Definition

    Arthrogryposis is the presence of nonprogressive, usually symmetric, congenital contractures of 2 or more different body areas. Arthrogryposis or arthrogryposis multiplex congenita are general terms that describe various syndromes that involve multiple contractures.

    Etiology

    Decreased fetal movement (fetal akinesia) in normally developing joints and limbs is hypothesized to be the cause of arthrogryposis. The lack of movement around the joint leads to the development of extra connective tissue formation around the joint.1 The extra connective tissue fixes the joint in place, eventually leading to the development of contractures. Maternal causes of fetal akinesia include fetal crowding, maternal illness, or toxins. Fetal causes include connective tissue or skeletal defects, vascular compromise, muscle defects, or neurologic defects. Some forms of arthrogryposis can be genetically inherited through autosomal dominant, autosomal recessive, de novo, X-linked, or mitochondrial mechanisms.

    Epidemiology including risk factors and primary prevention

    Arthrogryposis occurs in 1 in 3000 births.2 Males and females are equally affected. Risk factors include maternal illnesses, such as multiple sclerosis, diabetes mellitus, myasthenia gravis, and maternal hyperthermia in the first trimester. Severe bleeding during pregnancy or after a failed attempt at pregnancy termination has also been associated with arthrogryposis. Muscle disorders, muscular dystrophies, mitochondrial disorders, neural tube defects, or other central nervous system disorders are at an increased risk for arthrogryposis because of decreased movement. Abnormalities in connective tissue development may cause abnormal formation of the joints that can restrict joint movement. Regular prenatal care assists with early diagnosis of decreased fetal movement but does not improve incidence or outcome.

    Patho-anatomy/physiology

    The pathophysiology is related to the specific type of arthrogryposis. Exact mechanisms are not well understood in some subtypes of arthrogryposis. In general, fetal akinesia leads to collagen overgrowth, where extra connective tissue forms around the joint leading to the thickening of joint capsules. As movement is restricted, tendons become less pliable, bones become flattened, and there may be decreased limb growth, further increasing the contracture.

    In distal arthrogryposis, genetic anomalies are thought to cause alterations in the contractility of muscles, which leads to contractures. In vitro and in situ studies have demonstrated that in distal arthrogryposis, there are mutations in genes that encode troponin T, troponin I, and beta tropomyosin. These mutations increase ATPase and may alter calcium sensitivity, leading to increased contractility of developing fast twich muscles. The increased contractility then causes contractures.3 Alterations in the regulation of myosin heavy chains by the MYHC gene is also believed to be a cause of some forms of distal arthrogryposis.4

    In central etiologies, there may be decreased corticospinal tract activation of spinal cord motor neurons or spinal cord motor neurons may be directly injured.

    In congenital myopathies, there may be alterations in genes than encode mysosin light chains in skeletal muscle. Genetic alterations have also been observed in congenital myopathy and muscular dystrophy, which can affect A-type lamins and glycosylation, which can affect contractility.

    In mothers with myasthenia gravis, maternal antibodies may block the acetylcholine receptors in the fetus, which can decrease fetal movement and cause contractures.5

    Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

     

    Amyoplasia

    Distal Arthrogryposis

    Diastrophic Dysplasia

            

      Inheritance

    Sporadic

    AD/autosomal recessive

    Autosomal recessive

      Extremities affected

    Legs and arms

    Hands and feet

    Arms, legs, spine

      Other deformities

    Equinovarus feet

    Extended elbows

    Midfacial hemangioma

    Dislocated hips

    Scoliosis common

    Camptodactyly

    Overlapping fingers

    Ulnar deviation

    Foot deformities

    Short stature/dwarfism

    Elbow, finger, and hip contractures

    Cystic external ear mass

    Cleft palate

      Comments

    Symmetric involvement 

    Most common form of arthrogryposis

    10 subtypes based on hierarchy of phenotypes

    Type 2B (Sheldon Hall) syndrome most common

    High infant mortality rate; if survive beyond infancy--normal lifespan

     

    All arthrogryposis types:

    • Cognition/behavior: Cognition is typically normal if there is no underlying neurologic or developmental disorder.​​
    • Ambulation: Walking is often delayed until to 2-5 years old.
    • Scoliosis: Can be progressive if detected before 1 year of age.
    • Adults: an live normal lifespan, some become completely independent, others continue to require assistance
    Specific secondary or associated conditions and complications
    • Associated conditions and complications include:
      • Anesthesia risk:
        • Increased spinal cord injury risk because of underdeveloped first and second vertebrae (caution with anesthesia for surgery).
        • Malignant hyperthermia.
        • Increased risk for aspiration.
        • Scoliosis/kyphoscoliosis--occurs in 20-30% of arthrogryposis patients.
        • Arthritis.
        • Fractures of long bones. ​​
        • Constipation.
        • Feeding difficulties are common in early infancy and may persist through childhood.
    • Obesity -- although usually thin body habitus, overfeeding, and limited energy expenditure with severe contractures can increase the risk of obesity in infants, children, and adults.
  2. Essentials of Assessment
    History
    • Obstetric history
      • Maternal illness such as diabetes, infections, myasthenia gravis, exposure to toxins, and maternal fevers.
      • Prenatal ultrasound history--fetal movement, limb deformities, and amniotic fluid levels.
      • History of uterine abnormalities, gestational age, placental abnormalities, and breech presentation.
      • History of abortions, miscarriages, and stillbirths.
    • Family history of neurologic or genetic disorders and consanguinity.
    Physical examination

    Physical findings may vary and may include:

    • Limbs:
      • At least 2 or more joint contractures.
      • Limited active and passive range of motion.
      • Joint fusion-synostosis or soft tissue contractures.
      • Pterygium--winging in between joints.
      • Muscle atrophy.
      • Equinovarus or clubfoot deformities.
      • Deep grooves, tight bands, dimples--deep dimples especially over joints with decreased movement.
      • Hirsutism--areas with low activity.
      • Shortened digits or underdeveloped ends of digits.
      • Syndactyly--webbing of digits.
      • Abnormal finger position.
     
    • Trunk/spine/genitalia:
      • Scoliosis.
      • Cryptorchidism.
      • Hernia.
      • Hydrocele.
      • Underdeveloped labia.
     
    • Head/neck:
      • Webbed neck.
      • Abnormal head shape.
      • Scalp defects, abnormal hair pattern.
      • Midline facial hemangioma or birthmarks--especially in amyoplasia.
      • Ptosis.
      • Hypertelorism.
      • Cleft palate.
      • Flat bridge of nose, asymmetric facies.
      • Abnormal ear shape and folding.
     
    • Neurologic:
      • Abnormal reflexes--absent, diminished, or brisk.
      • Hypotonia may or may not be present.
      • Sensation generally intact.
      • Cognition--typically normal.
    Functional assessment
    • Functional history should include:
      • Developmental milestones.
      • Trunk/head control.
      • Mobility and activities of daily of living difficulties.
      • Fine motor difficulties.
      • Bracing, equipment, and home adaptations.
      • Articulation, feeding, and swallowing.
    • Functional assessment:
      • Range of motion.
      • Transfers, mobility, and gait.
      • Use of upper extremities for various tasks.
      • Gross and fine motor skill assessment.
    Laboratory studies

    Creatine phosphokinase--in generalized or progressive muscular weakness.

    Distal arthrogryposis genetic tests--TNNI2, TPM2, TNNT3, MYH8, and MYH3.

    Genetic testing for muscular dystrophies, spinal muscular atrophy, myopathies, and mitochondrial myopathies, if necessary.

    Chromosome analysis if indicated--consider referral to genetics for gene sequencing or microarray if unexplained dysmorphisms and intellectual disability.

    Maternal anitbody for myasthenia gravis

    Imaging

    Radiologic studies--x-rays, including pelvis x-ray in infants to evaluate hip joint, foot x-rays to determine vertical talus (in infants), and scoliosis x-rays, which can be done at any age, if indicated by clinical exam, they may need to be obtained every 6 months to 1 year depending on severity and progression.

    Magnetic resonance brain imanging of the brain and spinal cord, in order to rule out central or spinal cord anomalies.

    Supplemental assessment tools

    ​Muscle biopsy and electromyography/nerve conduction studies are often used to examine for neuromuscular etiologies. Diagnostic yield is higher when both studies are ordered and assessed together.6

    Environmental

    ​Environmental barrier assessment should include: the number of stairs around the home; accessibility of home, school, and community; and transportation needs.

    Social role and social support system

    ​Social history should include: the number of people in the home; primary and secondary caregivers; friends, hobbies, interests, and extracurricular activities; support/coping resources--patient, family, school, and community; and transition to adulthood needs and financial needs.

    Professional Issues

    ​Family planning--genetic counseling should be offered to parents to help them understand recurrence risks after having their first child with arthrogryposis of genetic etiology.

  3. Rehabilitation Management and Treatments
    Available or current treatment guidelines
    • Published treatment guidelines do not exist, but good practice suggests emphasis on the following areas:
    • Early intervention:
      • Active and passive range of motion to decrease severity of contractures.
      • Bracing and splinting.
      • Adaptive equipment and mobility devices.
    • Surgical interventions in first year if possible.
    • Repeat surgeries throughout childhood and adolescence to improve function:
      • Hand, wrist, and finger deformity corrections.
      • Scoliosis surgery.
      • Soft tissue releases, tenotomies, and tendon transfers.
      • Osteotomies--although there is a chance for recurrence of deformity.
      • Hip and knee flexion contracture release--community walkers found to have less than 20 degree contractures of knees and hips.7
    At different disease stages
    • 3-12 months:
      • Range of motion--passive and active, daily home stretching program.
      • Bracing/splinting--thermoplastic splints and serial casting; dynamic splints occasionally for elbow flexion.
      • Correction of foot deformities--4 weeks, Ponseti bracing, and surgery with the goal of plantigrade and braceable feet.
      • Correction of knee deformities--4 months.
      • Correction of hips--6-8 months.
      • Upper extremity surgeries ideally are performed between 3-12 months for better outcomes.8
    • Childhood
      • Continued range of motion/therapy.
      • Ongoing reassessment of bracing needs--night splints, serial casting, and dynamic wrist splints for supervised play.
      • Incorporation of adaptive equipment, mobility devices, and gait aids.
      • Repeat surgical interventions, if necessary.
      • Regular scoliosis screening--x-rays and clinical assessment.
      • Annual ophthalmology and hearing screens.
      • Peer support, teacher support, coping, and counseling, if needed.
    • Adolescent
      • Continued range of motion/therapy and home exercise program.
      • Bracing for functional purposes more than stretching.
      • Adaptive equipment for independence goals.
      • Scoliosis screening.
      • Goals for independence, career, vocation, and higher education.
    • Adults
      • Home stretching and exercise program.
      • Maintenance of functional bracing options.
      • Management and prevention of obesity, hypertension, diabetes, and other conditions that affect adult age groups.
      • Support, counseling, and family planning.​
    Coordination of care

    Ideally, a multidisciplinary approach should be incorporated. Team members may include healthcare professionals in pediatrics, genetics, orthopedics, physiatry, neurology, physical therapy, occupational therapy, speech therapy, orthotics, social work, psychology, nutrition, and nursing. Teachers and school therapists should also receive regular communication regarding the patient.

    Patient & family education

    Newborn: Family education regarding the diagnosis, implications, outcomes, and expectations.

    Children: When the child is old enough to start asking questions about his/her physical state, answers should be addressed appropriately. Provide parents with tools to facilitate educating their child on their diagnosis.

    Adolescents/adults: Education on healthcare and community resources.

    Risks and benefits of all interventions should be regularly communicated to families.

    Emerging/unique Interventions

    Arthrogryposis multiplex congenita evaluation disc-o-gram--range of motion and function of various joints are expressed as a percentage of normal and placed onto a spider web or star chart, which can track range of motion and functional improvement in relationship to various interventions.9

    Goniometry--active range of motion and passive range of motion are commonly used.

    Pediatric Outcomes Data Collection Instrument has been found useful in amyoplasia patients.10

  4. Cutting edge/emerging and unique concepts and practice
  5. Gaps in the evidence-based knowledge
    References
    1. Swinyard CA, Bleck EE. The etiology of arthrogryposis (multiple congenital contracture). Clin Orthop Relat Res. 1985;(194):15-29.
    2. Yang SS, Dohan-Oliel D, Monpetit D. Ambulation gains after knee surgery in children with arthrogryposis. J Pediatr Orthop. 2010;30:863-869.
    3. Robinson P, Lipscomb S, Preston LC, et al. Mutations in fast skeletal troponin I, troponin T, and beta tropomyosin that cause distal arthrogryposis all increase contractile function. FASEB J. 2007;21:896-905.
    4. Tajsharghi H, Kimber E, Kroksmark AK, Jerre R, Tulinius M, Oldfors A. Embryonic mysoin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally. Arch Neurol. 2008;65:1083-1090.
    5. Bamshad M, Van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg. 2009;91(Suppl 4):40-46.
    6. Kang PB, Lidov HG, David WS, et al. Diagnostic value of electromyography and muscle biopsy in arthrogryposis multiplex congenita. Ann Neurol. 2003;54:790-795.
    7. Fassier A, Wicart P, Douboussett J, Seringe R. Arthrogryposis multiplex congenita: long term follow up from birth to skeletal maturity. J Child Orthop. 2009;3:383-390.
    8. Mennen U, van Heest A, Ezaki M, Tonkin M, Gericke G. Arthrogryposis multiplex congenita. J Hand Surg Br. 2005;30:468-474.
    9. Mennen U. Arhtrogryposis multiplex congenita: functional classification and the AMC disc-o-gram. J Hand Surg Br. 2004;29:363-367.
    10. Courtney A, Spaeth MC, Chafey DH. Use of the pediatric outcomes data instrument to evaluate functional outcomes in arthrogryposis. J Pediatr Orthop. 2011;31:293-296.


    Bibliography

    1. Staheli LT, Hall JG, Jaffe KM, et al. Arthrogryposis: A Text Atlas. New York: Cambridge University Press; 1998.
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