Arthrogryposis

Author(s): Yuxi Chen, MD, Kyle Menze, DO , Hana Azizi, MD

Originally published:08/17/2012

Last updated:08/18/2016

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 proliferation of capsular connective tissue fixes the joint in place, eventually leading to 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, and peripheral or central nervous system (PNS, CNS) pathology. 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 from 1/3000 to 1/5000 live births.2,3 Males and females are equally affected. Muscle disorders, muscular dystrophies, mitochondrial disorders, neural tube defects, or other PNS and CNS disorders are at an increased risk for arthrogryposis. Neurogenic factors are the most common cause of fetal akinesia presented in 70-80% of arthrogryposis patients.2 Other 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, metabolic disease such as phosphofructokinase deficiency and drugs taken during pregnancy (e.g., muscle relaxants, misoprostol, cocaine, alcohol) can also be associated with arthrogryposis.4 Regular prenatal care assists with early diagnosis of decreased fetal movement but does not decrease incidence or improve 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 twitch muscles. The increased contractility then causes contractures.5 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.6

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 that 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 then impairs contractility.

In mothers with myasthenia gravis, maternal antibodies may block the acetylcholine receptors in the fetus, which can decrease fetal movement and cause contractures.7

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
Extremitiesaffected 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 (1/3) of arthrogryposis

10 subtypes based on hierarchy of phenotypes

Type 2B (Sheldon Hall) syndrome most common

High infant mortality rate; if survivebeyond infancy–normal lifespan

All arthrogryposis types:

1. Cognition/behavior: Cognition is typically normal if there is no underlying neurologic, chromosomal or developmental disorder.
2. Ambulation: Walking is often delayed until to 2-5 years old.
3. Scoliosis: Can be rapidly progressive if detected before 1 year of age.
4. Adults: can 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:

1. Increased spinal cord injury risk because of underdeveloped first and second vertebrae (caution with anesthesia for surgery).

2. Malignant hyperthermia.

3. Increased risk for aspiration.

4. Scoliosis/kyphoscoliosis.

5. Arthritis.

6. Fractures of long bones.

7. Constipation.

8. 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 such as myoma/fibroma or bicornate uterus, gestational age, multiple birth, 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 include:

Limbs:

  • At least 2 or more joint contractures in 2 different body areas.
  • Hip and knee flexion, shoulder adduction, elbow extension, wrist and finger flexion contractures are common.7 Joint fusion-synostosis or soft tissue contractures.
  • Pterygiumskin webs in between joints.
  • Muscle atrophy. Equinovarus or clubfoot deformities are most common. Congenital vertical talus, isolated equinus deformity, congenital metatarsus adductus, pes equinovalgus, or pes calcaneovalgus are occasionally seen as well.2
  • Deep grooves, tight bands, dimples (especially over joints with decreased movement).
  • Hirsutism: areas with low activity.
  • Shortened digits or underdeveloped ends of digits.
  • Syndactyly: webbing of digits.

Trunk/spine/genitalia:

  • Scoliosis develops in 30–62% patients.8
  • 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.
  • Micrognathia, 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. 25% of individuals have intellectual disability/CNS involvement. 4

Functional assessment

Functional history should include:

  • Developmental milestones.
  • Trunk/head control.
  • Activities of daily of living.
  • Gross and fine motor difficulties.
  • Bracing, equipment, and home adaptations.
  • Speech and swallowing difficulties, including feeding

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 antibody for myasthenia gravis

Imaging

Radiologic studies: x-rays, including pelvis x-rays 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, and may need to be obtained every 6 months to 1 year depending on severity and progression.

Magnetic resonance imaging 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.9 As more genetic markers are discovered for testing for arthrogryposis, the need for muscle biopsy may decrease in the future.

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:

  1. Active and passive range of motion to decrease severity of contractures.
  2. Strengthening any functional muscles.10
  3. Bracing and splinting.
  4. Adaptive equipment and mobility devices.

Surgical interventions in first year if possible.

Repeat surgeries throughout childhood and adolescence to improve function:

  1. Hand, wrist, and finger deformity corrections. Although shoulder surgery is rarely needed, a subcapital derotation osteotomy of the humerus can be beneficial for severe internal rotation contractures. 11
  2. Scoliosis surgery.
  3. Soft tissue releases, tenotomies, and tendon transfers. Osteotomies-although there is a chance for recurrence of deformity. The recurrence rate of foot deformities after primary surgery of the equinovarus foot may approach 75–100%2
  4. Hip and knee flexion contracture release-community walkers found to have less than 20 degree contractures of knees and hips.12

At different disease stages

3-12 months:

  1. Range of motion: passive and active, daily home stretching program.
  2. Bracing/splinting: thermoplastic splints and serial casting; dynamic splints occasionally for elbow flexion.
  3. Correction of foot deformities: 4 weeks. Ponseti bracing, and surgery with the goal of plantigrade and braceable feet to allow full weight bearing.
  4. Correction of knee deformities: 4 months. Knee extension contractures are more likely than flexion contractures to be successfully managed conservatively with a trial of casting.13
  5. Correction of hips-6-8 months.
  6. Upper extremity surgeries ideally are performed between 3-12 months for optimal outcomes.14

Childhood /adolescent

  1. Continued range of motion/therapy.
  2. Ongoing reassessment of bracing needs: night splints, serial casting, and dynamic wrist splints for supervised play and for functional purposes more than stretching.
  3. Incorporation of adaptive equipment, mobility devices, and gait aids.
  4. Repeat surgical interventions, if necessary.
  5. Regular scoliosis screening-x-rays and clinical assessment.
  6. Annual ophthalmology and hearing screens.
  7. Peer support, teacher support, coping, and counseling, if needed.
  8. Prepare adolescent to achieve goals for independence, career, vocation, and higher education.

Adults

  1. Home exercise program. Upper limb functions including gripping, reaching the head and face for feeding and hair care, reaching the perineal area for hygiene, and dressing, are the most important determinants of independent living for adult with arthrogyposis.12
  2. Maintenance of functional bracing options.
  3. Management and prevention of obesity, hypertension, diabetes, and other conditions that affect adult age groups.
  4. 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.15

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.16

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Many genetic factors may lead to arthrogryposis, including sporadic gene mutations, chromosomal disorders, and mitochondrial disorders. New research continues to identify possible causes of the condition, such as the ECEL1 gene causing a specific type of distal arthrogryposis.17

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Current management emphasizes a collaboration of surgical and rehabilitation intervention. It is possible that exome sequencing and other techniques may not only lead to further understanding, but to new prevention and treatment strategies in the future.

REFERENCES

  1. Swinyard CA, Bleck EE. The etiology of arthrogryposis (multiple congenital contracture). Clin Orthop Relat Res. 1985;(194):15-29.
  2. Kowalczyk B, Feluś J. Arthrogryposis: an update on clinical aspects, etiology, and treatment strategies. Arch Med Sci. 2016 Feb 1;12(1):10-24.
  3. Yang SS, Dohan-Oliel D, Monpetit D. Ambulation gains after knee surgery in children with arthrogryposis. J Pediatr Orthop. 2010;30:863-869.
  4. Kimer E. AMC: amyoplasia and distal arthrogryposis. J Child Orthop.2015 Dec;9(6):427-32.
  5. 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.
  6. 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.
  7. Bamshad M, Van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg. 2009;91(Suppl 4):40-46.
  8. Greggi T, Martikos K, Pipitone E, et al. Survival treatment of scoliosis in a rare disease: arthrogryposis. Scoliosis. 2010;5:24
  9. Kang PB, Lidov HG, David WS, et al. Diagnostic value of electromyographyand muscle biopsy in arthrogryposis multiplex congenita. Ann Neurol. 2003;54:790-795.
  10. Kroksmarck AK, Kimber E, Jerre R, et al. Muscle involvement and motor function in amyoplasia. Am J Med Gen A. 2006;140:1757-67.
  11. Zlotow DA, Kozin SH. Posterior elbow release and humeral osteotomy for patients with arthrogryposis.J Hand Surg Am. 2012;37:1078–82.
  12. 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.
  13. Murray C, Fixsen JA. Management of knee deformity in classical arthrogryposis multiplex congenita (amyoplasia congenita) J Pediatr Orthop B. 1997;6:186–91.
  14. Mennen U, van Heest A, Ezaki M, Tonkin M, Gericke G. Arthrogryposis multiplex congenita. J Hand Surg Br. 2005;30:468-474.
  15. Mennen U. Arhtrogryposis multiplex congenita: functional classification and the AMC disc-o-gram. J Hand Surg Br. 2004;29:363-367.
  16. 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.
  17. Nagata K., Kiryu-Seo S., Tamada, H., et al. ECEL1 mutation implicates impaired axonal arborization of motor nerves in the pathogenesis of distal arthrogryposis. Acta Neuropathol. 2016 Mar 7. [Epub ahead of print]

Bibliography

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

Hall JG. Arthrogryposis multiplex congenita: etiology, genetics, classification, diagnostic approach and general aspects. J Pediatr Orthop B. 1997;6: 159–66.

Dubousset J, Guillaumat M. Long-term outcome for patients with arthrogryposis multiplex congenital. J Child Orthop. 2015;9: 449-458.

Ayadi K, Trigui M, Abid A, et al. Arthrogryposis: clinical manifestations and management. Arch Pediatr. 2015;22(8): 830-9.

Original Version of the Topic:

Talia R. Collier, MD. Arthrogryposis. Publication Date: 2012/08/17.

Author Disclosure

Yuxi Chen, MD
Nothing to Disclose

Kyle Menze, DO
Nothing to Disclose

Hana Azizi, MD
Nothing to Disclose

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