Arthrogryposis

Overview

Arthrogryposis (arthrogryposis multiplex congenita – AMC) is not a separate medical entity, but rather a descriptive term for around 300 different disorders with varied etiologies. The occurrence of congenital, typically non-progressive joint contractures affecting at least two separate body locations is a defining trait.

This group of illnesses includes the so-called classic arthrogryposis – Amyoplasia, which has distinct clinical characteristics such as symmetrical, severe contractures involving both the upper and lower limbs. 

Arthrogryposis multiplex congenita

The word arthrogryposis is frequently used as abbreviation for numerous congenital contractures that affect two or more separate parts of the body. Arthrogryposis is a clinical finding, not a particular diagnosis, and it is seen in over 300 different illnesses. One in every 3000 live newborns is affected with arthrogryposis.

The heredity, natural history, treatment guidelines, and results of arthrogryposis differ amongst illnesses, emphasizing the significance of a precise diagnosis in each child. The goal of this page is to offer the most recent information on the classification, etiology, and care of children with various kinds of arthrogryposis.

Arthrogryposis takes its name from the Greek language ("arthron" – joint, "gryposis" – curvature); the word denotes a variety of congenital limb contractures that are normally non-progressive and often improve gradually with adequate care. 

Classification of Arthrogryposis

To develop a differential diagnosis, it is necessary to first determine whether a child's neurological function is normal. A normal neurological examination shows that the cause of arthrogryposis is:

• Amyoplasia, 
• Distal arthrogryposis,
• Generalized connective tissue disorder,
• Or fetal crowding. 

An faulty neurological examination, on the other hand, suggests that movement was reduced in utero due to a problem with the central or peripheral nerve system, the motor end plate, or muscle.

Amyoplasia

Amyoplasia (A = no; myo = muscle; plasia = growth) is a kind of arthrogryposis characterized by shoulders that are internally rotated and adducted, elbows that are extended, wrists that are flexed and ulnarly deviated, fingers that are stiff, and thumbs that are positioned in the palm.

The hips may be dislocated in the lower limbs, the knees are frequently extended, and the feet exhibit significant equinovarus contractures. A midfacial hemangioma is common in patients. The majority of patients are of average intellect. In one study, 10% of individuals developed abdominal abnormalities such gastroschisis or bowel atresia.

According to clinical studies, 84 percent of children had symmetric involvement of the upper and lower limbs; other presenting variants include upper limb exclusively, lower limb only, or asymmetric patterns of involvement.

Etiology

The pathological mechanism of congenital joint contractures typically involves the absence of active fetal movements (akinesia), which typically appears in the eighth week of fetal life. Fetal akinesia lasting more than 3 weeks may be sufficient to result in the absence of normal stretching of muscles and tendons acting on the affected joints, as well as reduced compliance of the joint capsule and periarticular ligaments, resulting in fibrosis and contractures of the affected joints.

The earlier restriction of active fetal motion occurs, the more severe the arthrogryposis; it is also thought that fibrosis of periarticular structures – both the ligaments and the articular capsule – may be responsible for the affected joints' tendency to return to their original fetal position despite treatment, i.e. deformity recurrence.

The direct reason producing akinesia in humans is unclear, however there are a variety of disorders that can result in interruption of active movement and, as a result, fetal akinesia.

These defects may affect the fetus and include functional and/or structural disorders that result in hypomobility, such as:

• Neurogenic factors (motor center diseases; disorders of the peripheral nerves or neuromuscular junction),
• Myogenic factors (muscular dystrophies, mitochondrial diseases),
• Diseases of the adjacent tissues and/or articular tissues (diastrophic dysplasia).
• Abnormalities that concern fetal environment:
• Maternal diseases (myasthenia gravis, SM, diabetes),
• Mechanical factors (anatomic abnormalities of the uterus; multiple pregnancy; oligohydramnios, amniotic bands),
• Vascular and nutritional disorders

Clinical features

Amyoplasia, classic arthrogryposis

As the name suggests, this is a sporadic multiple contractures syndrome characterized by symmetrical involvement of many joints in the lower and/or upper limbs and a specific posture of the limbs in the newborn. The function of the central nervous system is normal; muscular tissue is frequently replaced by adipose and fibrous tissues.

This form of congenital contracture is the most frequent in orthopedic clinical practice, with an incidence of 1/10,000 live births, accounting for around 30% of all congenital contractures. Patients with amyoplasia have normal or above-average IQ, and their projected 20-year survival rate is 94 percent; it is thought that they can live until middle and late age without the underlying illness causing failure of other organs.

However, without adequate therapy, their ability to ambulate independently and perform everyday tasks is limited. Appropriate comprehensive rehabilitative and surgical therapy leads in 85 percent of patients regaining ambulatory function by the age of 5 years. Apart from the degree of the contractures and the therapy utilized, this function is influenced by the power of the pelvic girdle and quadriceps muscles, as well as upper limb function.

Upper limb function and the capacity to execute personal care tasks are the most important factors in determining quality of life. According to studies, 75 percent of patients can eat themselves independently, but only around 10 percent can dress, 35 percent can wash, and 25 percent can take a bath on their own.

In 60–92% of cases, classic arthrogryposis is characterized by symmetric involvement of all limbs. Lower limb involvement is reported in 7–24% of patients, whereas upper limb involvement is observed in 1–13% of patients.

The following is the clinical picture found in the majority of individuals with typical four-limb involvement:

• The shoulder is internally rotated and adducted. Deltoid muscle function is impaired.
• The elbow: Most patients appear with elbow extension contracture with inadequate brachialis and biceps brachii function, resulting in absent or considerably reduced elbow flexion. Elbow flexion contracture is a less common occurrence. The elbow joint is cylindrical in shape and free of skin wrinkles.
• The wrist: The majority of patients appear with typical palmar flexion contracture, ulnar deviation, and hand pronation. Patients with myogenic arthrogryposis may manifest with wrist extension contracture.
• In classic arthrogryposis, hand contractures vary, but the most common feature is increasing distal flexion contractures of interphalangeal joints. Relative extension contractures in the metacarpophalangeal joints are possible. Normally, the thumb is adducted. Finger contractures are often stiff, and most patients have a considerable lack of active finger motions; nonetheless, children with AMC frequently show unexpected skills to complete everyday activities – even with minimal active finger mobility. It is possible to see "clenched fist" and "thumb in palm" abnormalities in syndromic arthrogryposis.
• Contractures of the hip are widespread; they are predominantly flexion, abduction, and external rotation contractures of different severity. About one-third of individuals experience unilateral or bilateral hip dislocation.
• The most frequent abnormality in the knee is flexion contracture of varied degree; extension contracture is less common and may be accompanied with knee dislocation. Flexion contracture is often coupled with a weak quadriceps and a "dimple" above the patella.
• Deformities of the ankle joint and foot are seen in virtually all AMC patients, with severe talipes equinovarus being the most prevalent; vertical talus may be seen less commonly. All of these malformations are distinguished by their great severity, difficulty in treatment, and high proclivity to return.
• The spine: aberrant curvatures are detected in around 28% to 67% of patients; most usually, these are simple long thoracolumbar curves without concurrent vertebral abnormalities; nonetheless, the curves frequently advance fast.
• Facial skeleton: hypoplasia of the mandible (micrognathia) is common; in severe AMC instances, rigidity and reduced function of the temporo-mandibular joints may be seen.

Distal Arthrogryposes

Distal arthrogryposes are an autosomal dominant category of illnesses that mostly affect the distal regions of the limbs. The study of the genetic and molecular underpinnings of distal arthrogryposis syndromes has provided a significant foundation for identifying genetic risk factors for congenital contractures.

Distal arthrogryposes are defined by congenital contractures of two or more separate body locations that are not caused by a main neurological or muscular illness. A similar pattern of hand and foot involvement, minimal involvement of proximal joints, and varying expressivity are characteristics shared by all distal arthrogryposes.

To diagnose a specific distal arthrogryposis, major diagnostic criteria are employed. Camptodactyly or pseudocamptodactyly (restricted passive proximal interphalangeal joint extension with hyperextension of the wrist), hypoplastic and/or nonexistent flexion creases, overriding fingers, and ulnar deviation at the wrist are significant diagnostic criteria for the upper limb.

Major diagnostic criteria for the lower limb include talipes equinovarus, calcaneovalgus deformities, vertical talus, and/or metatarsus varus. An person must fulfill two or more of these main criteria to be deemed affected, but when a first-degree family member (i.e., a parent or a sibling) meets these diagnostic requirements, additional family members with at least one major diagnostic criterion are considered affected.

Central Nervous System Causes of Arthrogryposis

Forebrain developmental abnormalities (e.g., hydranencephaly, microcephaly, or forebrain neuronal migration problems), whether caused largely by hereditary causes or as a result of fetal central nervous system infection, are occasionally linked with arthrogryposis.

Joint contractures are most likely caused by decreased corticospinal tract activity of spinal cord motor neurons in the majority of such instances. However, in other cases, the underlying illness directly damages spinal cord motor neurons, causing to embryonic hypomotility.

On clinical examination, such illnesses might be suspected if hyperreflexia, unilateral arthrogryposis, or cognitive deficiencies are present, and they can be physically located by magnetic resonance imaging of the brain.

Arthrogryposis can be caused by chromosomal deletions or rearrangements. Arthrogryposis is occasionally accompanied with developmental loss of facial and other brainstem motor neurons (e.g., Moebius syndrome). It is unknown whether the lack of limb movement in these children is related to defective corticospinal input to spinal cord motor neurons or to poor spinal cord motor neuron development.

Neuromuscular Causes of Arthrogryposis

Although genetic peripheral neuropathies with prenatal onset have been identified, they are an uncommon cause of arthrogryposis. Arthrogryposis can be caused by neuromuscular junction blockade in fetuses carried by women with myasthenia gravis, as well as autoantibodies that target fetal acetylcholine receptors.

Autoantibody suppression measures, such as maternal thymectomy before to pregnancy or intravenous gamma globulin injection during pregnancy, are expected to lower the incidence of arthrogryposis in such pregnancies. 

Botulinum toxin given to pregnant women has the theoretical ability to suppress acetylcholine release at neuromuscular junctions in the fetus and so induce fetal hypomotility, although no infants with arthrogryposis due to this etiology have been recorded. Arthrogryposis can also arise in newborns who have inherited abnormalities in genes encoding skeletal muscle acetylcholine receptor proteins or proteins related to these receptors.

Diagnosis

A diagnosis of Arthrogryposis is determined based on the presence of specific symptoms (for example, several congenital contractures), a complete patient history, and a thorough clinical investigation. Certain procedures, including as nerve conduction, electromyography, and muscle biopsy, may be required to discover the underlying etiology of AMC. These tests can assist detect neuropathic or myopathic illnesses.

A nerve conduction examination assesses the speed with which nerves convey an electrical impulse. An electromyography is a test that measures electrical activity in skeletal voluntary muscles both at rest and during contraction. A biopsy is a technique in which a tiny sample of damaged tissue is taken and examined under a microscope to discover typical alterations or abnormalities that might assist in the diagnosis.

Microarray and imaging investigations of the central nervous system (CNS) may potentially be beneficial in determining diagnosis. Because there are so many different mutations that might cause arthrogryposis, whole genome sequencing is sometimes necessary to make a diagnosis.

Use radiography to evaluate the following skeletal and joint abnormalities:

• Bony abnormalities
• Disproportionately short stature 
• Scoliosis
• Ankylosis
• Absence of patella
• Humeroradial synostosis

Ultrasonography can help in the detection of irregularities in the CNS and other viscera. The CNS and muscle mass may be assessed by computed tomography (CT) scanning. Magnesium resonance imaging (MRI) can be utilized to assess muscle mass that has been hidden by contractures.

The most significant diagnostic technique is most likely a muscle biopsy. It should be included in all autopsies as well as during surgery.

Management

The aims of first treatment are to move the joints, apply splints for improved posture and function, and offer physical and occupational therapy as well as instructions to the child's caretakers so that home therapy may be provided. Most children's lives include ongoing therapy sessions, with 80 percent of children with amyoplasia getting therapy services throughout their adolescence.

Persistent limb abnormalities that impair function are prevalent and are frequently addressed surgically. In one study of children with amyoplasia, orthopaedic procedures were performed on 76 percent of the children's feet, 39 percent on their knees, and 18 percent on their hips. The elbows were operated on in 24% of the youngsters, the wrists in 16%, the hands in 8%, and spinal surgery was necessary in 5%.

The key long-term aims of amyoplasia therapy include enhanced joint mobility and muscular strength, as well as the development of adaptive usage patterns that allow for walking and independence with everyday tasks. Fixed joint contractures that prevent or interfere with upper-limb function may necessitate surgical intervention.

Shoulder contractures are seldom treated surgically; however, if internal rotation of the shoulder particularly prevents effective placement of the hand in space, an external humeral rotational osteotomy is suggested. A posterior capsulotomy of the elbow with triceps lengthening can be used to address an inability to extend the hand to the mouth caused by an elbow extension contracture.

To provide active elbow flexion, many tendon transfers have been performed. However, a recent research called into doubt the long-term effectiveness of elbow flexion transfers in this group, and the authors advocated for elbow capsulotomy without tendon transfer.

To retain the arc of motion but reposition the wrist in extension and neutral deviation, a dorsal carpal wedge osteotomy with a potential flexor carpi ulnaris tendon transfer has been documented for the wrist. Thumb-in-palm deformity surgical repair may enhance thumb position for pincer function.

Surgical management of upper limb contractures

The upper limb should be thought of as a functioning unit. The ultimate objective of treatment is to restore the patient's personal care and use of communication equipment (e.g., telephone, computer, pen) or assistive devices for ambulation (crutches, walker, wheelchair, car). Similarly to the lower limbs, it is critical to begin conservative therapy of upper limb contractures during the newborn and early infancy period.

Surgery on the shoulder joint is rarely necessary; however, a subcapital derotation osteotomy of the humerus might be useful, especially in severe internal rotation contractures.

Complication of surgery 

All of these methods carry complication risks, such as the development of elbow flexion contracture, and their indications should be carefully considered, as treatment failure may result in general functional deterioration, particularly if the patient relies on the upper limbs for independent ambulation, such as with crutches or a wheelchair.

Severe palmar flexion wrist contractures necessitate surgical soft tissue releases on the palmar side, distal radius wedge bone resections, or wrist arthrodesis. Transferring the flexor to extensor tendons is an option for flexion contractures that are not susceptible to passive treatment.

The indications for these treatments should also be carefully examined, since some people can function normally while having flexion wrist contractures. Thumb repair operations (adduction contractures) or deepening of the initial interdigital gap may be required in some circumstances.

Arthrogryposis life expectancy

The lifetime of someone with arthrogryposis is often normal, however it might be shortened by heart anomalies or central nervous system difficulties. In general, children with amyoplasia have a fair prognosis, albeit most require years of rigorous care.

Conclusions

Congenital contractures are a frequent birth condition that cause significant morbidity and economic burden. An important field of pediatric health-care research is attempting to uncover the origin and pathology of congenital contractures.

Arthrogryposis refers to a group of congenital contractures that can be seen in over 300 distinct illnesses. When the results of a neurological examination are normal, Amyoplasia and the distal arthrogryposis syndromes, of which there are at least ten distinct varieties, are prevalent causes of arthrogryposis.

Amyoplasia is a sporadic condition, whereas the distal arthrogryposes are autosomal dominant. Arthrogryposis can also be caused by central nervous system anomalies, peripheral nervous system problems, or intrinsic muscle illnesses. These can be attributed to either hereditary or environmental causes.

Any condition that reduces fetal mobility might, in theory, produce congenital contractures, thus detecting these causes should be rather simple. Indeed, several environmental (e.g., uterine congestion) and genetic (e.g., trisomy 18) variables that induce congenital contractures have been identified. However, the fundamental etiology of most congenital contractures is still being researched.

Children with amyoplasia generally have significant joint contractures as well as muscular weakness. The capacity to walk and execute activities of daily life has been reported to be as high as 85 percent after several orthopaedic and rehabilitation procedures. Nonetheless, children with amyoplasia often require more surgical treatments than children with any other kind of arthrogryposis, and the majority of adults require assistance with daily living activities.

Most arthrogryposis contractures require treatment, which may include multiple surgical corrections of the knees and hips, correction of spinal deformities, elbow and wrist contractures, foot deformities, and dislocations that frequently accompany the contractures; the hip and knee are the most commonly affected joints.

The treatment of a child, and then an adult, with arthrogryposis is difficult – not only because of the nature of the disease and the resulting surgical technical difficulties, but also because of the complex multi-disciplinary treatment, which involves, among others, pediatricians, physiotherapists, geneticists, orthopedic surgeons, and orthotic specialists – all of whom require extensive knowledge and experience in the treatment of arthrogryposis.