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Arthrogryposis multiplex congenita (AMC)

Introduction

 Arthrogryposis multiplex congenita literally means a congenital anomaly in the newborn involving multiple curved joints. Although first described by Otto in 1841, Sheldon in 1932 published the first detailed description and called the condition as 'amyoplasia congenita'. It is important to recognize that arthrogryposis is a descriptive term and not an exact diagnosis as there are at least 150 possible underlying causes.
Hall et al in 1985 considered three main groups

  1. Classical arthrogryposis multiplex congenital in which the limbs are primarily involved and the muscles are deficient or absent ("amyoplasia").
  2. Arthrogryposis in association with major neurogenic (brain, spinal cord, anterior horn cell or peripheral nerve) or myopathic (congenital muscular dystrophy, myopathy, toxic myopathy) dysfunction.
  3. Arthrogryposis in association with other major anomalies and specific syndromes such as diastrophic dysplasia or craniocarpotarsal dystrophy.

Hall noted an incidence of classic arthrogryposis multiplex congenita of 1 in 10,000 live births.  In Helsinki, an incidence of 3 per 10,000 live births was reported while there was only one case in 56,000 live births in Edinburgh. Based on an apparent increase in the incidence in the 1960s, Wynne-Davies et al have suggested an infective cause for this rare condition.

Clinical features

  • Multiple rigid joint deformities with defective muscles but normal sensation. Rigidity of several joints in each case resulting from both short tight muscles and capsular contractures. There may be presence of 'pterygium' on flexor aspects of contracted joints. There is often absence or fibrosis of muscles or muscle groups.
  • Normal intellectual development in most cases.
  • All four limbs are involved in the classical form (amyoplasia congenita) but the condition can also occur only in the upper limbs or only in the lower limbs.
  • An autosomal dominant variant called distal arthrogryposis was described by Hall, in which the hands and feet are severely deformed with only minor contractures more proximally and possible development of scoliosis.
  • In addition to the multiple joint contractures, the lack of skin creases (cylindrical or tubular limbs), and deep dimples over the joints are very characteristic.
  • There is dislocation of joints, most commonly the hip but occasionally the knee.
  • The trunk is rarely affected.
  • Other congenital anomalies such as cryptorchidism, hernias, gastroschisis may occur.

Etiology

  • Arthrogryposis is multifactorial in etiology.
  • Factors liable to produce immobility of the fetus in-utero may contribute to congenital contractures. Some of these include; structural abnormality of the uterus (bifid, large fibroids), oligohydramnios, increased intrauterine pressure, mechanical compression of the fetus, weak fetal movements, breech presentation and prematurity.
  • Inflammatory or infective etiology has also been postulated. These include inflammation in joint, muscle, spinal cord or brain, Rubella in early pregnancy and infection with unknown viruses.
  • Whittem proposed on the basis of animal studies that the primary condition is a degeneration of the anterior horn cells occurring in the early months of gestation.
  • Wynne-Davies et al noted an interesting case of a pregnant mother treated with curare for severe tetanus who gave birth to an arthrogrypotic baby. They thus postulated and environmental theory and labeled this as 'environmental disease of early pregnancy' associated with one or more unfavorable intrauterine factors.

Diagnosis

  • Clinical examination remains the best modality for establishing the diagnosis of arthrogryposis. We have found a few factors that are often useful in making a diagnosis. Although not absolute criteria, they are helpful when considered in combination.
  • Unlike paralytic disorders, joint deformities of AMC are usually stiff or rigid from the beginning, with incomplete passive range of motion.
    1.      Deformities of arthrogryposis tend to be symmetric.
    2.      The severity of contractures tends to increase as one reaches the periphery of the limb. More proximal joints tend to be less involved and the trunk is frequently spared. The worse deformities tend to occur in the hands and feet.
  • Although arthrogrypotic features are a clinical diagnosis, the clinician must try to establish an etiological diagnosis.
  • The orthopedist, neurologist, geneticist and pediatrician must participate in diagnosing and managing this condition.
  • Radiographs of the involved extremities with joint involvement are recommended. These may demonstrate congenital bony abnormality, loss of subcutaneous fat and muscle. Radiographs of the whole spine will identify any vertebral anomalies.  CT/MRI of the brain is useful in establishing or ruling out structural CNS involvement.
  • Electromyography and nerve conduction studies are of limited value and have been used to differentiate the peripheral neuropathic from the myopathic variants.
  • A skeletal muscle biopsy is needed when a primary myopathic disorder is suspected, unless genetic testing can establish the diagnosis by molecular testing of DNA from peripheral blood.
  • Plasma creatine kinase estimation may be done to exclude myopthic disorders.  This is best checked on day of life 3 or after, once any transient initial increase in CK from the birth process has subsided.
  • If a prenatal ultrasound detects an absence of fetal movement, especially in combination with polyhydramnios, the diagnosis of arthrogryposis can be suspected.
  • Histologic analysis reveals a small muscle mass with fibrosis and fat between the muscle fibres. Myopathic and neuropathic features may overlap in the same specimen. The periarticular soft tissues are fibrotic.
  • Genetic consultation, with chromosome analysis and collagen studies, should be considered in cases where is distinct peripheral neuromuscular disorder is not readily apparent.

Prognosis

  • The clinician should be able to derive a general prognosis and treatment plan once the diagnosis of AMC is established.
  • There may be a few functional motor movements as one reaches the periphery of the limb. Vigorous occupational therapy and use of hand splints and serial casting can improve the range of motion and functional use of the hand in many cases of AMC where the etiology is not of a progressive disorder, e.g. amyoplasia.  Surgery, in selected cases, is necessary to obtain a more neutral positioning of the wrist and fingers so the limited degree of strength can be used to optimal biomechanical advantage.
  • Recurrence of a corrected deformity is quite common and is known to occur with growth in a limb in which the periarticular structures are incapable of stretching.
  • Arthrogrypotic children have certain positive factors, however, which must be utilized in their successful management.
  1. Joint instability is not a problem in Arthrogryposis unlike other paralytic conditions.
  2. With coordinated and team approach in management, there will often be little deterioration from the condition at birth.
  3. There is frequently central sparing and a relatively normal trunk.
  4. The child with normal CNS findings can be expected to have reasonably normal intelligence and with enough motivation, can contribute to successful management.

Management

Principles of management

It is important to see these patients as early as possible and start treating the deformities early, as some of them will respond remarkably well to physiotherapy, stretching and splintage.

  • Musscle balance is usually less of a problem than in other paralytic neuromuscular conditions and is easier to achieve. Muscle balance should be possibly established if there are functioning muscles available for transfer.
  • Recurrence of deformity is the rule because the dense, inelastic soft tissues about the joints do not properly elongate with growth. These structures are considered the key to the successful management of arthrogryposis in the growing child. The surgical implication of this is; farther the surgery is performed from the joint, less likely it is to be of lasting benefit. In soft-tissue release surgeries therefore, tenotomies alone are likely to fail if they are not accompanied by capsulotomies. Again, osteotomies to correct deformity or transfer the range of motion to a more useful arc are beneficial, but only at or near skeletal maturity, or the deformity will promptly recur with growth.
    • Maximum safely obtainable correction should be achieved at the time of surgery.
    • The use of wedging or corrective casts after surgery is of little additional benefit.
  • Range of movement: Results from passive ROM stretching varies. Aggressive treatment may result in an appreciable increase in the limited range of joint movement or have little impact. The arc of motion however, can often be changed into a functionally better position. For example, a fixed flexion deformity of the knee can be changed in to an extended position with manipulation even though the range is not increased.
  • Centrifugal involvement. The severity of the deformity increases towards the periphery of the limb and the more proximal joints tend to be less involved. Central sparing of the trunk may be noted in most cases. The clinical implication of this is that the useful tendons for transfer are more likely to be found proximally. Also an uninvolved and flexible trunk may be an asset during training and rehabilitation.
  • Aim of management. The main aim of management is to achieve maximum functional gain for each patient. Minimum requirements are independent walking, self-care, and ideally, the ability to eventually be gainfully employed.
  • Staging and timing of surgical procedures. We believe that the maximum benefit from surgical reconstruction of a limb with arthrogryposis is achieved by careful staging of procedures.
  1. The disabling deformity and contractures should be corrected in the first stage.
  2. The major joints should be then put in a functional arc of motion most adapted to the patient's needs.
  3. In the final stage tendon transfers are occasionally required to bring motor power to a joint that has been put to its optimum position. The elbow joint is well suited to tendon transfers and has been widely noted to give satisfactory results.

SCOLIOSIS

  • In consistency with the principle that the severity of the stiffness and deformity increases towards the periphery of limbs and that the more central or proximal areas are less involved, we believe that central sparing is an important clinical observation.
  • A straight, supple and well-balanced trunk is an important asset in this otherwise crippling disorder and every effort should be made to maintain this.
  • Although relative sparing of the trunk is typical, scoliosis occurs frequently in arthrogryposis because of high incidence of congenital curves. Also scoliosis associated hip contractures and pelvic obliquity occur frequently.
  • Idiopathic scoliosis. Genetic or idiopathic scoliosis seems to occur as frequently in the arthrogrypotic population as in the general population. The progression and behavior of an idiopathic curve in arthrogryposis is possibly the same as in other children although, may be more crippling because of the coexisting peripheral deformities.
  • Paralytic scoliosis: Long paralytic scoliotic curves are sometimes seen in children with typical neuropathic type of arthrogryposis. Some forms of congenital muscular dystrophy include a "rigid spine" component. The curve is typically seen before the second year of life and progresses to become long, severe and eventually rigid. Well-controlled bracing is the treatment of choice in younger children although surgical management may be necessary in progressive cases.
  • Congenital scoliosis: These curves are common in arthrogryposis. This is probably consistent with the fact that other congenital anomalies are also common in arthrogryposis. Failure of vertebral formation and failure of segmentation have been noted. Klippel-Feil deformity is also found in these patients. These curves must be observed closely and aggressive treatment like early surgical fusion may be indicated in the presence of asymmetrical progressive curves.
  • Scoliosis associated with pelvic obliquity: This is frequently associated with neglected hip deformities that lead to femoro-pelvic obliquity and is potentially avoidable. Unilateral hip deformity should be particularly watched for and corrected. The trunk can then be kept supple and straight.

LOWER LIMBS

Foot involvement

  • The most severe deformities in arthrogryposis are known to occur in the foot.
  • The rigid foot deformity is usually the clubfoot or equinovarus deformity and less frequently, a congenital vertical talus deformity.
  • The goal of treatment is conversion of the rigid deformed foot into a rigid plantigrade foot.
  • Principle: Correction of the hind foot takes precedence over the forefoot. If heel equinus and varus deformities are corrected, the forefoot deformity usually does not cause a hindrance in walking.
  • Serial stretching (casting) may sometimes produce a degree of correction. Once it is clear during the course of treatment that conservative treatment will not be successful, surgery should be considered, preferably when the child is ready to walk and ambulate.
  • An extensive posteromedial and posterolateral release is recommended.  If the foot fails to correct with even the most extensive soft-tissue release or relapses quickly within 2-3 years, talectomy may be considered.
  • Talectomy has been successful in giving good results in these stiff and rigid feet.  The talus is best approached through a lateral incision as in case of a triple arthrodesis. We advocate the following principles during surgical correction:
    1. Excision of the talus must be complete as any cartilaginous fragments left behind may grow and cause recurrence of the deformity.
    2. The calcaneus must be positioned below the tibia. Recurrence is common if the posterior release is inadequate, or if the tibio-calcaneal reduction is not obtained. We advocate tenotomy of the Achilles tendon, in which a segment of the tendon is excised to facilitate the reduction of the calcaneus under the tibia.
    3. During surgery, if total talectomy is found to be inadequate, then if required the navicular bone may also be excised to correct the deformity.
    4. Talectomy should be followed by immobilization in plaster for at least 10-12 weeks.
  • Recurrence of deformity after talectomy is often difficult to treat. Radical secondary soft tissue release may be required in such cases. Persistent forefoot adduction may require a calcaneo-cuboid fusion in symptomatic cases. Wedge excision osteotomy in the tarsal region may be useful in the correction of plantaris and cavus deformities. The foot must be sufficiently skeletally mature before osteotomies so that fusion rate is high.
  • The Ilizarov technique and apparatus does offer an opportunity to correct these deformities by gradual distraction and neohistiogenesis. Applications of this fixator in the pediatric foot have been fairly successful and satisfactory.
  • In case of older children with neglected or relapsed equinovarus deformity, correction can be best obtained by triple arthrodesis. We have found this to be one of the most dependable methods of surgical treatment. Although we have performed this surgery in children as young as 10 years we prefer to wait till the child is 12 years old. Recurrence is uncommon with this procedure. In rare cases of recurrence of the deformity after triple arthrodesis (at the level of the ankle) a pantalar arthrodesis may be offered by an easy conversion of the triple arthrodesis. A supra-malleolar osteotomy is contraindicated during growth as it invariably fails and is best offered as the last line of defense in the skeletally mature patient.
  • Feet deformities with rigid congenital vertical talus may require a thorough posterior release, reduction of the talo-navicular dislocation and lengthening of the tight lateral structures. A satisfactory plantigrade position can be established in most cases but again stiffness is common squeal.

Knee joint

  • Both common presentations of the knee deformity, fixed flexion or fixed extension, should be initially treated with repeated stretching and splintage.
  • The goal is to get the knees straight and to keep them that way by bracing. Extension of the knee if considered the key to later walking. If a flexed knee is neglected, postural hip flexion contractures are likely to ensue. Combined contracture in both hips and knees is not compatible with good gait.
  • Non-surgical management: Manipulation and plaster casting in the younger child has been successful in a large population of our patients. It is important to note that although the arc of motion is changed to a more extended position, the range is not increased. Even if complete extension may not be obtained, the knee joints are usually stable and mild flexion deformities are quite compatible with a good gait pattern.
  • Surgical management:
  • Deformities not responding to soft-tissue stretching may need surgical intervention.
  • It is advisable to plan the timing of knee surgery in keeping with the treatment plan for the foot. For example, if the foot requires immobilization with the knee flexed then the knee flexion correction should be staged subsequent to the foot management. On the other hand if the knee is in fixed extension it is better to correct the knee extension before operation on the foot, so that the foot can be immobilized with a flexed knee.
  • The main principle in knee surgery in arthrogryposis is to transfer the fixed arc of knee movement into the most useful range as a significant gain in the range is often not achievable.
  • Surgeries for release of fixed flexion often involve extensive soft-tissue release of all posterior structures except the neurovascular bundle at the back of the knee. Medial and lateral incisions may be used instead of a midline longitudinal incision so as to minimize problems with wound healing. Serial plasters with gradual stretching in the post-operative period are extremely helpful in achieving further knee extension. Long-term splintage is then required to maintain the knee position.
  • In older children when here is a risk of vascular compromise with extensive soft-tissue release and stretching, bony shortening (of the lower femur) may be performed to achieve adequate knee extension. On the other hand, osteotomies for the correction of deformities in arthrogryposis should be delayed until near skeletal maturity to avoid progressive or recurrent deformity.
  • Fixed hyperextension of the knee may respond reasonably well to serial stretching and casting. In severe cases that fail to respond to stretching, an extensive muscular release with quadricepsplasty may be necessary to correct the knee position. Splintage and knee support are likely to be required on a long-term basis.
  • The Ilizarov fixator again provides a useful alternative to surgical release or in cases of failed surgery especially in the older patient.

Hip joint

  • A common finding at birth in arthrogrypotic patients is stiffness of the hips in flexion, abduction and external rotation.
  • The two most common involvements of the hips are fixed contractures and hip dislocation.
  • Fixed contractures in arthrogryposis of the hips tend to be in the 'Frog' position with severe abduction and external rotation components. These are sometimes more of a problem than hip dislocations. They are a hindrance in walking/ ambulating and can be difficult to treat.
  • Management: It is important to correct the knee deformity before attempting any surgical intervention and correction at the hip. With knee correction at an early stage, the results of hip deformity correction are encouraging. In some cases surgical release may be required and should be carefully weighed in keeping with the presentation of the whole lower limb and not just the hip joint. For example, in a patient with contractures of the hip and knee, failure to correct the flexed knee will lead to failure of hip surgery.
  • Surgical treatment:
  1. Growing child: Full correction is not easily obtainable with soft tissue release procedures. There are often adhesions around the femoral neck, and total capsulectomy carries with it the risk of avascular necrosis. Also, subtrochanteric osteotomy in the growing child usually fails. Recurrence is usually unavoidable with skeletal growth.
  2. Skeletally mature child: If the child is able to ambulate with compensatory lordosis, it is best to wait until skeletal maturity and then hope for lasting correction with subtrochanteric osteotomy.
  • Arthrogryposis may lead to unilateral or bilateral dislocation of hips. Dislocations are usually stable and, if the pelvis is well balanced, are also consistent with a good gait. Treatment of hip dislocation is often not easy as closed reduction invariably fails, and stiffness and persistent flexion deformity usually follow open reduction. Diagnosis can be difficult clinically as the marked stiffness may be a limiting factor for demonstrating the hip instability clinically.
  • If the hips are dislocated, in most cases they are not reducible on abduction and should not be splinted if irreducible. Splinting in such cases may lead to avascular necrosis.
  • Bilateral dislocations tend to be high and stable, are usually symmetrical and tend to have a fairly balanced pelvis. This is often consistent with a good gait and it may be advisable to leave them alone as it is often not possible to get a satisfactory result on both sides and in fact may lead to more stiffness with a high chance of redislocation.
  • In cases of unilateral dislocation, there is a risk of progressive pelvic obliquity and secondary scoliosis. We therefore believe it is often worth reducing the dislocated hip especially in the infant and the younger child. Open reduction should be done as soon as the child is healthy enough and knee flexion contractures have been controlled. Excessive delays make the procedure more technically demanding and the reduction more difficult to achieve.

UPPER LIMBS
Unlike management of lower limbs where independent walking is the main goal, management of upper extremities in arthrogryposis requires considerable caution, as prognosis for successful treatment is more dependent on extent of deformity and on patient's intelligence. The minimum requirements for the patient are ability to feed and attend to personal hygiene.

Timing

Again, in contrast to the lower limbs where surgery cannot be postponed due to risk of delayed walking, operations on upper limbs can be postponed for several years. Interestingly arthrogrypotic children develop a remarkable ability to get about well with their upper limbs in spite of the complexities of these deformities, developing a surprising amount of dexterity, and therefore surgical intervention if at all should be weighed very carefully in these cases.

Planning

  • Both limbs should be considered as a unit: The general principle that the arc of joint motion can be changed but not increased should be remembered. A reasonable expectation at the end of treatment is that the patient should ideally be able to move one hand to his mouth and the other to his anus, but still be capable of opposing both hands. This is important to consider because children with severe hand deformities and weakness depend on the integrated use of both hands (bimanual opposition) to perform any task that normal people do with one hand. In addition, he must be able to push himself out of a chair.
  • Shoulder and elbow joints should be considered as a unit. The rotation of the shoulder is an important factor on which the axis of the elbow joint motion largely depends. Therefore, if elbow surgery is contemplated to enable the hand to reach the mouth, a severely fixed and internally rotated shoulder should also be simultaneously corrected.
  • Procedures performed in one joint may affect another.
  • In our experience we have noticed that Steindler's flexoroplasty performed to achieve motor power for the elbow increases flexion contractures of the wrist and fingers.
  • Carpectomy performed for wrist deformity may improve flexion contractures of the fingers by causing relative lengthening of the long flexors.
  • Physiotherapy has a major contribution in obtaining motion in the stiff joints along with stretching and splintage. Detailed assessment by a physical therapist and occupational therapist is necessary before embarking upon any surgical intervention and surgery should be possibly deferred until the age of 4 years.

 Shoulder joint

  • The typical deformity is adduction and internal rotation. Although shoulder weakness is common, these children can develop remarkable trick movements and therefore surgical intervention may rarely be indicated.
  • Adduction itself is not troublesome, since usually there is enough passive abduction for self-care, and surgery is rarely required. Fixed internal rotation at the shoulder can in some cases jeopardize the axis of elbow motion. In severe cases a simple external rotation osteotomy may be performed in the upper humerus to bring the forearm and hand into a more functional position.

Elbow joint

  • The two common involvements of the elbow noted are; fixed extension contracture and fixed flexion contracture. Both these conditions respond well to stretching and physical therapy and can be well controlled in infancy.
  • Once the child is ambulating, activities such as crutch walking, toileting, and push-off from chair/seated position essentially need active elbow extension. Therefore it is important to inadvertently damage the active extension mechanism while intending to improve active flexion.
  • Passive flexion can be surgically achieved by a posterior soft-tissue release of the elbow, lengthening of the triceps, and a posterior capsular and collateral ligament release. This can restore a very useful arc of motion and further procedures may not be even necessary in most cases.
  • In candidates where a value of increased active flexion can be established, active power could be provided in multiple ways:
  1. A Steindler's flexorplasty procedure advancing the flexor origin up the humerus with possible reinforcement with extensor origin advancement may be performed. This can essentially be performed only if the flexor and extensor group of muscles are sufficiently strong.
  2. Transfer of the triceps tendon to the radius may be performed and can become a strong and active flexor. However there is loss of active extension, which could lead to severe functional impairment in most cases.
  3. Pectoralis major muscle transfer has also been proposed for achieving active elbow flexion although may not be possible in some cases in view of the technical difficulties (absent biceps tendon) or extensive and unacceptable scar.
  • Elbow and forearm soft tissue contractures can be successfully corrected using the Ilizarov fixator in many cases.


Wrist and Hand

  • The wrist is often involved in a flexion contracture and the fingers may be curved and stiff as well. Thumb adduction deformity (thumb-in-palm) is also common.
  • Manipulation, stretching and splintage (especially early on) can be very important in establishing mobility and range. Interestingly the flexed position of the wrist is very functional and may not need intervention. Surgical corrections involving partial or complete carpectomy have been described and often show high incidence of recurrence of deformity with growth.
  • Finger stiffness is extremely difficult to correct in these cases and surgery is rarely indicated. Most patients adapt extremely well to the finger stiffness and are impressive in their functioning abilities. Release of thumb adductors and web space enlargement is very useful in correcting the thumb deformity.
  • Wrist arthrodesis for functional or cosmetic gain may be considered at or near skeletal maturity.

Summary

Early recognition and counseling of parents is extremely important in this condition, which could be extremely distressing both to the parents and the patients. There is a tendency for the deformity to recur throughout growth and, therefore, long-term stretching, splintage and orthoses are often necessary. The classical form of the condition being non-progressive with intact sensations, patients benefit significantly from proper choice of surgery and can remain active and functional in adult life.

References

Neuromuscular Texts

  • Color Atlas of Muscle Disorders in Childhood. Dubowitz, V.  Chicago: Year Book Medical Publishers, Inc., 1989.  A superb out of print atlas with pictures and brief descriptions of the main neuromuscular disorders of childhood. Find it in your medical library.
  • Muscle Disorders in Childhood, 2nd ed.  Dubowitz, V. Philadelphia: W B Saunders; 1995. A more detailed description of pediatric neuromuscular disorders, including many of the newer genetic discoveries.
  • Muscle Diseases ed. Schapira, AHV and Griggs, RC. Blue Books of Practical Neurology, vol 24. Boston: Butterworth-Heinemann; 1999. An excellent more recent text on both genetically based and acquired muscle diseases in children and adults.
  • Myology, 2nd ed. Edited by Engel A and  Franzini-Armstrong C, 1994 McGraw-Hill, New York. A detailed two-volume reference text.

Professional Resources:

  • Neuromuscular Disorders, V. Dubowitz ed., journal published 8/year. Amsterdam: Elsevier Science, Pergamon Press. The weblink provides monthly updates on an extensive listing of gene locations for nuclear and mitochondrial mutations for inherited myopathies, dystrophies, neuropathies, ion channel disorders, ataxias and congenital myasthenic syndromes.
  • For clinical trial information: www.cc.nih.gov/nihstudies and www.centerwatch.com.
  • Arthrogryposis - Orthopaedic Web Links (OWL)

Patient Resources:

  • Adaptive Recreational Organizations: Adventures in Movement for the Handicapped (aimkids @siscom.net) and  American Alliance for Health, Physical Education, Recreation and Dance (www.aahperd.org)
  • Arthrogryposis Multiplex Congenita, AVENUES support group: www.sonnet.com/avenues

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