Close
Close

Arthrogryposis

Arthrogryposis multiplex congenita, AMC

Overview

Arthrogryposis multiplex congenita refers to the development of multiple joint contractures affecting two or more areas of the body prior to birth. It derives its name from Greek, literally meaning "curving of joints" (arthron, "joint"; grȳpōsis, late Latin form of late Greek grūpōsis, "hooking"). Children born with one or more joint contractures have abnormal fibrosis of the muscle tissue causing muscle shortening, and therefore are unable to perform passive extension and flexion in the affected joint or joints. AMC has been divided into three groups: amyoplasia, distal arthrogryposis, and syndromic. Amyoplasia is characterized by severe joint contractures and muscle weakness. Distal arthrogryposis mainly involves the hands and feet. Types of arthrogryposis with a primary neurological or muscle disease belong to the syndromic group.

A contracture occurs when a joint becomes permanently fixed in a bent or straightened position, which can impact the function and range of motion of the joint and may lead to muscle atrophy. AMC is not a specific diagnosis, but rather a physical symptom that can be associated with many different medical conditions. It is suspected that AMC is related to decreased fetal movement during development which can have a variety of different causes, including environmental factors (i.e. maternal illness, limited space), single gene changes (autosomal dominant, autosomal recessive, X-linked), chromosomal abnormalities and various syndromes. Treatment varies based on the signs and symptoms found in each person, but may include physical therapy, removable splints, exercise, and/or surgery.

Classification:

Some of the different types of AMC include:

  • Arthrogryposis multiplex due to muscular dystrophy.
  • Arthrogryposis ectodermal dysplasia other anomalies, also known as Cote Adamopoulos Pantelakis syndrome, Trichooculodermovertebral syndrome, TODV syndrome and Alves syndrome.
  • Arthrogryposis epileptic seizures migrational brain disorder.
  • Arthrogryposis IUGR thoracic dystrophy, also known as Van Bervliet syndrome.
  • Arthrogryposis-like disorder, also known as Kuskokwim disease.
  • Arthrogryposis-like hand anomaly and sensorineural deafness.
  • Arthrogryposis multiplex congenita CNS calcification.
  • Arthrogryposis multiplex congenita distal (AMCD), also known as X-linked spinal muscular atrophy type 2
  • Gordon Syndrome, also known as Distal Arthrogryposis, Type 2A.
  • Arthrogryposis multiplex congenita, distal type 2B, also known as Freeman-Sheldon syndrome variant.
  • Arthrogryposis multiplex congenita neurogenic type (AMCN). This particular type of AMC has been linked to the AMCN gene on locus 5q35. Arthrogryposis multiplex congenita pulmonary hypoplasia, also with a large number of synonyms.
  • Arthrogryposis multiplex congenita whistling face, also known as Illum syndrome.
  • Arthrogryposis multiplex congenita, distal type 1 (AMCD1).
  • Arthrogryposis ophthalmoplegia retinopathy, also known as Oculomelic amyoplasia.
  • Arthrogryposis renal dysfunction cholestasis syndrome, also known as ARC Syndrome.

Symptoms - Arthrogryposis

Arthrogryposis multiplex congenita refers to the development of multiple joint contractures affecting two or more areas of the body prior to birth. A contracture occurs when a joint becomes permanently fixed in a bent or straightened position, which can impact the function and range of motion of the joint. In some cases, only a few joints are affected and the range of motion may be nearly normal. In people who are severely affected, every joint in the body can be involved, including the jaw and back. Muscles of affected limbs may be atrophied or underdeveloped. Soft tissue webbing may develop over the affected joint.

AMC is not a specific diagnosis, but rather a physical symptom that can be found in many different medical conditions. The signs and symptoms associated with AMC can, therefore, vary greatly in range and severity depending on the underlying condition.

Almost every joint in a patient with arthrogryposis is often affected; in 84% of cases, all limbs are involved; in 11% only the legs; and in 4% only the arms are involved. Every joint in the body has typical signs and symptoms like the shoulder (internal rotation), wrist (volar and ulnar), hand (fingers in fixed flexion and thumb in palm), hip (flexed, abducted and externally rotated, frequently dislocated), elbow (extension and pronation) and foot (clubfoot). The range of motion capability can be different between joints because of the different deviations. Some types of arthrogryposis like amyoplasia have a symmetrical joint/limb involvement, with normal sensations. The contractures in the joints sometimes result in reduced walking development in the first 5 years. The intelligence is normal to above normal in children with amyoplasia. But it is unknown how many of these children have an above normal intelligence and there is no literature available about the cause of this syndrome. There are a few syndromes, like the Freeman-Sheldon and Gordon syndrome, which have craniofacial involvement. The amyoplasia form of arthrogryposis is sometimes accompanied with a midline facial hemangioma. Arthrogryposis is not a diagnosis but a clinical finding, meaning this disease is often accompanied with other syndromes or diseases. These other diagnoses can be found in every single organ in a patient. There are a few slightly more common diagnoses such as pulmonary hypoplasia, cryptorchidism, congenital heart defects, tracheoesophageal fistulas, inguinal hernias, cleft palate, and eye abnormalities.

Causes - Arthrogryposis

The exact cause of arthrogryposis multiplex congenita is not fully understood. AMC is thought to be related to decreased fetal movement during development, which can occur for a variety of reasons. When a joint is not moved for a period of time, extra connective tissue may grow around it, fixing it in place. Lack of joint movement also means that tendons connected to the joint are not stretched to their normal length, which can make normal joint movement difficult.

In general, there are four causes for decreased fetal movement before birth:

  • Abnormal development of muscles. In most cases, the specific cause for this cannot be identified. Suspected causes include muscle diseases, maternal fever during pregnancy, and viruses which may damage the cells that transmit nerve impulses to the muscles.
  • Insufficient room in the uterus for normal movement. For example, multiple fetuses may be present, the mother may lack normal amounts of amniotic fluid or there may be uterine structural abnormalities.
  • Malformations of the central nervous system (the brain and/or spinal cord). In these cases, arthrogryposis is usually accompanied by a wide range of other symptoms.
  • Tendons, bones, joints or joint linings may develop abnormally. For example, tendons may not be connected to the proper place in a joint.

AMC can be a component of numerous condition caused by environmental factors, single gene changes (autosomal dominant, autosomal recessive, X-linked), chromosomal abnormalities and various syndromes.

Arthrogryposis multiplex congenita is not inherited in most cases; however, a genetic cause can be identified in about 30% of affected people. It can be a component of many different genetic conditions, including those caused by a single gene change or a chromosomal abnormality, such as trisomy 18. Genetic conditions sometimes associated with AMC include some connective tissue disorders; muscle disorders such as muscular dystrophies or congenital myopathies; and certain mitochondrial disorders. Depending on the underlying genetic cause, it may be inherited in an autosomal recessive, autosomal dominant or X-linked manner. Some cases are thought to have multifactorial inheritance, which means that both genetic and environmental factors may play a role in causing the condition.

Research on arthrogryposis has shown that anything that inhibits normal joint movement before birth can result in joint contractures. Arthrogryposis could be caused by genetic and environmental factors. In principle: any factor that curtails fetal movement can result to congenital contractures. The exact causes of arthrogryposis are unknown.

Extrinsic factors

The malformations of arthrogryposis can be secondary to environmental factors such as: decreased intrauterine movement, oligohydramnios (low volume or abnormal distribution of intrauterine fluid), and defects in the fetal blood supply. Other causes could be: hyperthermia, limb immobilization and viral infections. Myasthenia gravis of the mother leads also in rare cases to arthrogryposis. The major cause in humans is fetal akinesia. However, this had been disputed lately.

Intrinsic factors

Arthrogryposis could also be caused by intrinsic factors. These includes molecular, muscle- and connective tissue development disorders or neurological abnormalities.

Molecular basis

Research has shown that there are more than 35 specific genetic disorders associated with arthrogryposis. Most of those mutations are missense, which means the mutation results in a different amino acid. Other mutations that could cause arthrogryposis are: single gene defects (X-linked recessive, autosomal recessive and autosomal dominant), mitochondrial defects and chromosomal disorders (for example:trisomy 18). This is primarily seen in distal arthrogryposis. Mutations in at least five genes (TNN12, TNNT3, TPM2, MYH3 and MYH8) could cause distal arthrogryposis. There could be also connective tissue, neurological or muscle development disorders.

Muscle and conective tissue developement disorders

Loss of muscle mass with an imbalance of muscle power at the joint can lead to connective tissue abnormality. This leads to joint fixation and reduced fetal movement. Also muscle abnormalities could lead to a reduction of fetal movement. Those could be: dystrophy, myopathy and mitochondrial disorders. This is mostly the result of abnormal function of the dystrophin-glycoprotein-associated complex in the sarcolemma of skeletal muscles.

Neurological abnormalities

70-80% of the cases of arthrogryposis are caused by neurological abnormalities. Most of these result from an underlying genetic syndrome, or are due to environmental factors.

The underlying aetiology and pathogenesis of congenital contractures, particularly arthrogryposis and the mechanism of the mutations, remains an active area of investigation. Identifying these factors could help to develop treatment and congenital identification of arthrogryposis.

Prevention - Arthrogryposis

Genetic advice can be essential to prevent arthrogryposis. The risk of intrinsically derived contractures recurrence depends on the aetiology, extrinsical ones have a low reccurrence risk.

Diagnosis - Arthrogryposis

There is currently a lot of research on prenatal diagnosis. Prenatal diagnosis can be made in approximately 50% of fetuses presenting arthrogryposis. It could be found during routine ultrasound scanning showing a lack of mobility and abnormal position of the fetus. Nowadays there are more options for seeing details and structures, like the use of 4D ultrasound. In a clinic, a child can be diagnosed with arthrogryposis via physical examination confirmed by ultrasound, MRI, or muscle biopsy.

Prognosis - Arthrogryposis

There is still little literature available about the prognosis of a patient with arthrogryposis. The search for a prognostic factor is difficult, because of the small number of patients. But there are a few factors that seem to have an influence on the prognosis like the progressive muscle activity improvement. Results of a study showed an increase in strength during growth after the recovery of a passive range of motion in a useful arc. Other positive prognostic factors for independent walking were active hips and knees, hip flexion contractures of less than 20 degrees and knee flexion contractures less than 15 degrees without severe scoliosis.

The long-term outlook (prognosis) for people with arthrogryposis multiplex congenita (AMC) depends on the severity of the condition, the underlying cause, and the affected person's response to therapy. The degree to which muscles and joints are affected varies significantly from person to person. AMC can be associated with a variety of conditions that are each characterized by unique symptoms.

In general, many people affected by AMC have a good prognosis. With physical therapy and other available treatments, substantial improvement in joint function and mobility is normally possible. Most people with AMC are of normal intelligence and are able to lead productive, independent lives as adults.

Treatment - Arthrogryposis

The treatment of arthrogryposis multiplex congenita varies based on the signs and symptoms present in each person and the severity of the condition. Early in life, physical therapy to stretch contractures can improve the range of motion of affected joints and prevent muscle atrophy. Splits can also be used in combination with these stretching exercises. For most types of arthrogryposis, physical and occupational therapy have proven very beneficial in improving muscle strength and increasing the range of motion of affected joints.

Some patients, however, have persistent functional difficulties despite a rigorous physical therapy regimen. In these cases, surgery may be recommended to achieve better positioning and increase the range of motion in certain joints. Rarely, tendon transfers have been done to improve muscle function.

The treatment of arthrogryposis includes occupational therapy, physical therapy, splinting and surgery. The primary long-term goals of these treatments are increasing joint mobility and muscle strength and the development of adaptive use patterns that allow for walking and independence with activities of daily living. Since arthrogryposis includes many different types, the treatment varies between patients depending on the symptoms. Only a few good articles exist in which a surgical technique that is used to treat arthrogryposis is described. These surgeries are explained below.

Wrist Surgery in Arthrogryposis

Children with the amyoplasia type of arthrogryposis usually have flexed and ulnarly deviated wrists. Dorsal carpal wedge osteotomy is indicated for wrists with excessive flexion contracture deformity when non-surgical interventions such as occupational therapy and splinting have failed to improve function. On the dorsal side, at the level of the mid carpus, a wedge osteotomy is made. Sufficient bone is resected to at a minimum be able to put the wrist in a neutral position. If the wrist is also ulnarly deviated, more bone can be taken from the radial side to correct this abnormality. This position is held into place with two cross K-wires. In addition, a tendon transfer of the extensor carpi ulnaris to the extensor carpi radialis brevis may be performed to correct ulnar deviation or wrist extension weakness, or both. This tendon transfer is only used if the extensor carpi ulnaris appears to be functional enough.

Thumb Surgery in Arthrogryposis

The soft tissue envelope in congenital contractual conditions such as clasped or arthrogrypotic thumbs is often deficient in two planes, the thumb-index web and the flexor aspect of the thumb. There is often an appearance of increased skin at the base of the index finger that is part of the deformity. This tissue can be used to resurface the thumb-index web after a comprehensive release of all the tight structures to allow for a larger range of motion of the thumb. This technique is called the index rotation flap. The flap is taken from the radial side of the index finger. It is proximally based at the distal edge of the thumb-index web. The flap is made as wide as possible, but still small enough to close with the excessive skin on the palmar side of the index finger. The flap is rotated around the tightest part of the thumb to the metacarpophalangeal joint of the thumb, allowing for a larger range of motion.

Other Surgeries

Many other surgeries are also able to improve function in joints of arthrogryposis patients. These surgeries usually exist out of tendon transfers and skin flap movements, adjusted to the individual patient.

Resources - Arthrogryposis

  • NIH
Videos
Currently no videos.
To submit one, CLICK HERE