Arthrogryposis

The major cause of arthrogryposis is fetal akinesia (ie, decreased fetal movements) due to fetal abnormalities (eg, neurogenic, muscle, or connective tissue abnormalities; mechanical limitations to movement) or maternal disorders (eg, infection, drugs, trauma, other maternal illnesses). Generalized fetal akinesia can also lead to polyhydramnios, pulmonary hypoplasia, micrognathia, ocular hypertelorism, and short umbilical cord.

During early embryogenesis, joint development is almost always normal. Motion is essential for the normal development of joints and their contiguous structures; lack of fetal movement causes extra connective tissue to develop around the joint. This results in fixation of the joint, limiting movement and further aggravating the joint contracture. Contractures secondary to fetal akinesia are more severe in patients in whom the diagnosis is made early in pregnancy and in those who experience akinesia for longer periods of time during gestation.

Frequency

United States

The frequency is about 1 in 3000 live births.[3, 4]

International

Arthrogryposis multiplex congenita is more common in isolated populations such as Finland and the Bedouin community in Israel.[5]

Mortality/Morbidity

The life span of affected individuals depends on the disease severity and associated malformations but is usually normal. About 50% of patients with limb involvement and central nervous system (CNS) dysfunction die in the first year of life.

Scoliosis may compromise respiratory function. A retrospective study by Li et al found that arthrogryposis patients with concomitant scoliosis have worse pulmonary function than do individuals with adolescent idiopathic scoliosis. In study patients with arthrogryposis/secondary scoliosis, mean values for forced vital capacity (%FVC), forced expiratory volume in 1 second (%FEV1), and the ratio of FEV1 to FVC (%FEV1/FVC) were 48.8, 45.3, and 92.1, respectively, compared with 70.3, 69.7, and 96.9, respectively, for subjects with adolescent idiopathic scoliosis.[6]

A literature review by Cirillo et al indicated that in patients with arthrogryposis, adults have a greater tendency to experience pain than do children, with self reports of pain being more common in individuals in whom multiple corrective procedures have been performed.[7]

Race

No racial predilection has been described.

Sex

Males are primarily affected in X-linked recessive disorders; otherwise, males and females are equally affected.

Age

Arthrogryposis is detectable at birth or in utero using ultrasonography.

Family history

Review the history of children with arthrogryposis and other affected family members. Look for the presence of hyperextensibility, dislocated joints, dislocated hips, and clubfeet in other family members. Inquire about increased incidence of congenital contractures in second-degree and third-degree relatives.

Consanguinity increases the chance that both parents carry the same disease gene. Consanguinity is more common in families with rare recessive diseases than in those with common recessive diseases.

Some chromosomal abnormalities dramatically increase with maternal age, and single-gene dominant mutations can increase with paternal age.

Look for marked intrafamilial variability; the parent may be very mildly affected or may have had contractures early in infancy. Review previous miscarriages or stillbirths.

Pregnancy history

Infants born to mothers affected with myotonic dystrophy, myasthenia gravis, or multiple sclerosis are at risk. A mother with congenital myotonic dystrophy may have a child who inherits the gene and is severely affected with resistant contractures. A mother with myasthenia gravis or multiple sclerosis can have children with congenital contractures.

Maternal infections (rubella, rubeola, coxsackievirus, enterovirus) can lead to CNS or peripheral nerve destruction with secondary congenital contractures. Protracted or severe nausea may suggest maternal viral infection or encephalitis.

Maternal fever of more than 39°C for an extended period or maternal hyperthermia can cause contractures due to abnormal nerve growth or migration. This can be caused by prolonged soaking in hot tubs or hot baths.

Exposure to teratogens, such as drugs, alcohol, curare, methocarbamol, and phenytoin, may lead to decreased fetal movement.

Oligohydramnios or chronic amniotic fluid leakage may cause fetal constraint and secondary deformational contractures. Polyhydramnios may suggest fetal compromise (ie, defect in swallowing) and is a poor prognostic sign if associated with fetal hydrops.

Ask about uterine abnormalities such as bicornuate uterus with a septum or uterine fibroid.

Ask if the mother had large fibroids or other tumors, severe hypotension at a critical time, or severe hypoxia (eg, carbon monoxide poisoning) during pregnancy.

Review abnormal fetal movements such as decreased fetal movements, fetal kicking in one place, and decreased rolling.

Other complications that may be related to contractures include bleeding, abnormal fetal lies, threatened abortion, attempted termination, and trauma, such as a blow to the abdomen. An abnormal fetal lie may be a clue to intrauterine joint contractures.

Delivery history

Delivery history is usually atypical because of abnormal fetal presentation or difficulty due to the fixed fetal joints.

Breech or transverse fetal position is relatively common. Length of gestation is usually normal, but induction of labor is often prolonged. A limb is fractured during traumatic delivery in about 5-10% of cases.

Check for abnormal placenta, membranes, or cord insertion in cases that involve amniotic bands or vascular compromise. The umbilical cord may be shortened or wrapped around a limb, leading to compression.

Arthrogryposis epidemics have been reported, but whether these are due to chance occurrence, environmental factors, or infectious agents is unclear. Any clustering of children born with congenital contractures should be investigated.

In multiple births or twins, lack of movement due to uterine crowding can cause contractures. The death of one twin may lead to vascular compromise in the remaining twin.

Although joint contractures and associated clinical manifestations vary from case to case, several characteristics are common, including the following:

• Involved extremities are fusiform or cylindrical in shape, with thin subcutaneous tissue and absent skin creases

• Deformities are usually symmetrical, and severity increases distally, with the hands and feet typically the most deformed

• Joint rigidity may be present

• The patient may have joint dislocation, especially the hips and, occasionally, the knees

• Atrophy may be present, and muscles or muscle groups may be absent

• Sensation is usually intact, although deep tendon reflexes may be diminished or absent

A retrospective study by Hansen-Jaumard et al of children with arthrogryposis found less proximal joint involvement in youngsters with distal arthrogryposis than in patients with amyoplasia or in those who were classified as “other.” Contractures of the shoulder and elbow were also less common in distal arthrogryposis. Foot deformities and ankle contractures were quite prevalent in all patient groups, at rates of 91.5% (amyoplasia), 85.7% (distal arthrogryposis), and 83.3% (other).[49]

Contractures

Points to consider include the following (see the images below):

• Distal joints are affected more frequently than proximal joints

• Observe flexion versus extension, limitation of movement (fixed vs passive vs active), and characteristic position at rest; note the severity of all limitations. Distinguish between complete fusion or ankylosis and soft-tissue contracture

• Range of motion in the jaw is frequently limited

• Intrinsically derived contractures are frequently associated with polyhydramnios; the contractures are symmetrical and accompanied by taut skin, pterygia across joints, and a lack of flexion creases; recurrence risk and prognosis depend on etiology

• Extrinsically derived contractures are associated with positional limb anomalies, large ears, loose skin, and normal or exaggerated flexion creases; patients have an excellent prognosis and a low recurrence risk

The hands of a patient with contractural arachnodactyly (Beals syndrome). Note the long, thin fingers with interphalangeal joint contractures.

A girl with an autosomal recessive type of multiple pterygium syndrome. Note the multiple joint contractures at the knees with marked pterygia, including intercrural webbing, affecting her stance and ambulation.

Deformities

Limb deformities include pterygium, shortening, webs, compression (eg, due to cord wrapping), absent patella, dislocated radial heads, and dimples.

Facies deformities include asymmetry, flat nasal bridge, and hemangioma. Jaw deformities include micrognathia and trismus. See the image below.

A mother and child both affected with trismus pseudocamptodactyly. Note the small mouth (with limited ability to open) and flexion contractures of fingers on dorsiflexion.

Other deformities include scoliosis, genital deformities (cryptorchidism, lack of labia, microphallus), and hernia (inguinal, umbilical).

Other features of the fetal akinesia sequence include intrauterine growth retardation, pulmonary hypoplasia, and craniofacial anomalies such as hypertelorism, cleft palate, depressed nasal tip, high nasal bridge, functional short gut with feeding problems, and short umbilical cord.

Absent or distorted crease abnormalities are a result of aberrant form or function in early hand or foot development. See the image below.

An infant with distal arthrogryposis type I. Note medially overlapping fingers, tightly clenched fists, and positional foot contractures.

Malformations

Craniofacial malformations may involve the CNS (structural malformations, seizures, intellectual disability), skull (craniosynostosis, asymmetry, microencephaly), eyes (small and malformed eyes, corneal opacities, ptosis, strabismus), and palate (high, cleft, submucous cleft).

Respiratory problems include tracheal and laryngeal clefts and stenosis. Hypoplasia, weak muscles, or hypoplastic diaphragm may affect lung function.

Limb malformations include deletion anomalies, radioulnar synostosis, syndactyly, and shortened digits.

Skin vasculature abnormalities may cause hemangiomas and cutis marmorata; distal limbs may be blue and cold.

Cardiac problems include congenital anomalies and cardiomyopathy. The kidneys, ureters, and bladder may have structural anomalies.

Nervous system problems include loss of vigor; lethargy; sluggish, brisk, or absent deep tendon reflexes; and sensory deficits.

Muscle malformations include decreased muscle mass, soft muscle texture, fibrous bands, abnormal tendon attachments, and muscle changes over time.

Connective tissue abnormalities

Skin webs (pterygia) across joints, with limitation of movement, are common. Skin dimples are common over joints where movement is limited.

Skin may be soft, doughy, thick, or extensible. Subcutaneous fat is decreased or increased. Inguinal, umbilical, or diaphragmatic hernias may be present. Thickness in joints, symphalangism, and abnormalities in tendon attachment and length may also be present.

Associated skin defects include scalp defects, amniotic bands on limbs, and nail defects.

Pretibial linear skin indentation may be a sign of autosomal recessive inheritance or at least a sign for an increased risk of recurrence.

Arthrogryposis is presumed to be multifactorial in etiology.[8] In most cases, arthrogryposis multiplex congenita (AMC) is not a genetic condition. However, in approximately 30% of cases, a genetic cause can be identified.[9]

Arthrogryposis is a physical sign in many specific medical conditions. It can be a component of numerous conditions caused by environmental agents, single gene defects (autosomal dominant, autosomal recessive, X-linked recessive), chromosomal abnormalities, known syndromes, or unknown conditions. The principal cause is persistently decreased fetal movements (fetal akinesia) due to either fetal or maternal abnormalities.

The molecular basis of most genetic causes is not yet determined. However, the following 5 genetic loci associated with autosomal recessive arthrogryposis multiplex congenita have been described to date using a linkage analysis approach[10, 11] :

• Lethal congenital contracture syndrome (OMIM 253310) (9q34) - This is characterized by early fetal hydrops and akinesia, Pena-Shokeir phenotype, multiple pterygia and fractures, and a specific neuropathology in the spinal cord

• Neurogenic type of arthrogryposis multiplex congenita (OMIM 208100) (5q35) - This is a nonprogressive, nonlethal, multiple joint contracture described in a large Israeli-Arab inbred kindred

• Arthrogryposis-renal dysfunction-cholestasis syndrome (OMIM 208085) (15q26.1) - This is a neurogenic arthrogryposis multiplex congenita with renal tubular dysfunction and neonatal cholestasis, with bile duct hypoplasia and low gamma glumyl transpeptidase activity, leading to death within the first year of life

• Lethal congenital contracture syndrome (LCCS) type 2 (OMIM 607598) (12q13) - This is a lethal arthrogryposis multiplex congenita characterized by multiple joint contractures and micrognathia, normal duration of pregnancy, markedly distended urinary bladder, and lack of hydrops, pterygia, and fractures; it is prevalent in a large inbred Israeli-Bedouin kindred

• A novel autosomal recessive LCCS type 3 - This is similar to LCCS2 but lacks the urogenic bladder defect; the genetic defect leading to this syndrome was mapped to 3.4 Mb on chromosome 19p13, and it was shown that LCCS3 results from a mutation in PIP5K1C (GenBank accession number NM_012398)

Neuropathic abnormalities are the most common cause of arthrogryposis. They may include malformations or malfunctions of the central and peripheral nervous systems. Abnormalities include meningomyelocele, anencephaly, hydranencephaly, holoprosencephaly, spinal muscular atrophy, cerebrooculofacial-skeletal syndrome, and Marden-Walker syndrome.

Muscle abnormalities (malformations or malfunctions) are relatively rare causes of arthrogryposis. Some associated diseases include congenital muscular dystrophies, congenital myopathies, intrauterine myositis, and mitochondrial disorders.

Wallach et al, in a study of 42 children with arthrogryposis, found that in 19.1% of patients, the condition had a neurologic etiology, mainly involving polymicrogyria, while in 9.5% of the group, the disease arose myopathically.[12]

A study by Chareyre et al of 82 patients with arthrogryposis found that neuromuscular disorders were the most prevalent cause, at 39%, including involvement of the skeletal muscles (23%), peripheral nerves (13%), or neuromuscular junctions (4%). The cause rates for central nervous system and connective tissue disorders were 23% and 6%, respectively, with 8.5% of cases caused by mixed mechanisms and 22% of cases unable to be classified.[50]

Connective tissue abnormalities in tendon, bone, joint, or joint lining may develop in such a way that restricts fetal movements, resulting in congenital contractures. Examples include synostosis, lack of joint development, aberrant fixation of joints (as in diastrophic dysplasia and metatropic dwarfism), aberrant laxity of joints with dislocations (as in Larsen syndrome), and aberrant soft tissue fixations (as in popliteal pterygium syndrome). In some forms of distal arthrogryposis, the tendon develops normally but fails to attach to the appropriate place around the joint or bone. This results in abnormal lack of movement of the joints with secondary contractures at birth.

Limited space for fetal movement inside the uterus may contribute to the development of contractures. Examples include multiple births, uterine structural abnormalities, oligohydramnios in renal agenesis, and early persistent leakage of amniotic fluid.

Intrauterine vascular compromise may result in a loss of function in nerve and muscle with development of fetal akinesia and secondary joint contractures. Examples include severe maternal bleeding during pregnancy and failed attempts at termination of pregnancy.

See the list below:

• Obtain creatine phosphokinase (CPK) levels when the following conditions are present:

  • Generalized weakness

  • Doughy or decreased muscle mass

  • Progressive worsening

• Viral cultures may reveal an infectious process.

• Immunoglobulin M levels and specific viral titers (eg, coxsackievirus, enterovirus) in the newborn may reveal intrauterine infection.

• Maternal antibodies to neurotransmitters in the infant may point to the presence of myasthenia gravis.or recurrent affected pregnancies without diagnosis.

• Patients should undergo genetic evaluation and genetic workup that includes, but is not be limited to, chromosome studies/comparative genomic hybridization (CGH) array analysis.

• Cytogenetic study is indicated in the following situations:

  • Multiple organ or system involvement

  • Presence of CNS abnormalities, such as microcephaly, intellectual disability, lethargy, degenerative changes, or eye anomalies

• Consider performing a fibroblast chromosome study if lymphocyte chromosome levels are normal and the patient has intellectual disablity without diagnosis.

• Nuclear DNA mutation analysis is used to identify certain disorders, such as spinal muscular dystrophy.

• Mitochondrial mutation analysis is used to identify certain disorders, such as mitochondrial myopathy.

• Metabolic screening can be conducted in patients with hepatosplenomegaly, renal dysfuction, cholestasis, liver anomalies, hydrops, failure to thrive, or hypotonia.

Use photography to document the extent of deformities (range of motion and position of arthrogryposis) and to assess progress during treatment.

Use radiography to evaluate the following skeletal and joint abnormalities:

• Bony abnormalities (eg, gracile bones, fusions, extra or missing carpals and tarsals)

• Disproportionately short stature (ie, skeletal dysplasias)

• Scoliosis

• Ankylosis

• Absence of patella

• Humeroradial synostosis

Ultrasonography can help in evaluating the CNS and other viscera for anomalies. Ultrasonography also establishes potential muscle tissue.

A study by Dicke et al of the efficacy of obstetric ultrasonography in detecting fetal limb abnormalities indicated that the modality had an 81.3% sensitivity for the prenatal diagnosis of arthrogryposis. The investigators examined cases of arthrogryposis, polydactyly, limb reduction defects, and abnormal hand position, that underwent obstetric ultrasonographic scanning at their institution over a 20-year period.[29]

CT scanning can be used to evaluate the CNS and the muscle mass. MRI can be used to evaluate muscle mass obscured by contractures.

Prenatal assessment of a fetus with arthrogryposis is as follows[30] :

• Pregnancy history

• Family history

• Imaging studies of multiple contractures with ultrasound: For mechanisms extrinsic to the fetus, investigations include serial ultrasound assessment, parental examination, fetal MRI, and delivery planning. For mechanisms intrinsic to the fetus, investigations include karyotype and/or DNA testing, serial ultrasound assessment, parental examination, fetal MRI, referral to other specialties, and delivery planning. Other conditions may include primary CNS disease, primary muscular disease including amyoplasia, connective-tissue disorder, skeletal dysplasia, vascular disruption, and Pena-Shokeir phenotype.

First trimester prenatal ultrasound findings are as follows[31] :

• Total fetal immobility: Suspect lethal arthrogryposis.[32]

• Talipes and bilateral fixed flexion deformities of the hands, wrists, elbows, and knees: Suspect lethal arthrogryposis.[33]

• Abnormal flexion of the hips and extension of the knees: Suspect Pena-Shokeir phenotype (lethal).[34]

• Increased nuchal translucency: This is a useful marker, especially when there is a syndrome present, and is correlated with lethal arthrogryposis multiplex congenita.

• Cystic hygroma associated with multiple contractures: Suspect lethal multiple pterygium syndrome when other characteristic findings such as ocular hypertelorism, hypoplastic lungs, cleft palate, and hydramnios are present.[35]

Second trimester prenatal ultrasound findings are as follows[31] :

• Joint contracture of all the extremities with clinched hands, clubfeet, and, essentially absent fetal movements, often associated with polyhydramnios and pulmonary hypoplasia: Suspect lethal types of arthrogryposis.

• Cystic hygroma associated with pleural effusion: This is a common early second trimester finding in both lethal and nonlethal types of arthrogryposis multiplex congenita.

• Fetal hydrops: Possibly suspect lethal types of arthrogryposis.

• Arthrogryposis and decreased fetal mobility associated with multiple congenital anomalies: Suspect a possible syndrome.

Third trimester prenatal ultrasound findings are as follows[31] :

• Multiple joint contractures and other deformities such as talipes: This may not become apparent until the third trimester.

• Decreased fetal movement, micrognathia, polyhydramnios, hypoechogenicity, and hypomineralization of the long bones[36] ; pleural effusions; ventriculomegaly; hydronephrosis; and collapsed stomach: These may be common sonographic findings in the third trimester.

See the list below:

• Perform an ophthalmologic evaluation for opacity and retinal degeneration.

See the list below:

• Skin biopsy - This is rarely performed, being carried out if the patient has a history of intellectual disability with no known diagnosis.

• Muscle biopsy

  • Muscle biopsy is probably the most important diagnostic procedure. It should be included in all autopsies and at time of surgery.

  • Distinguish myopathic from neuropathic conditions by obtaining muscle specimens from normal and affected areas.

  • Special histopathologic and electron micrographic studies are used to evaluate fatty and connective tissue replacement of muscle fibers and variations in fiber size, such as decreased fiber diameter. All are nonspecific signs of muscle atrophy.

• Electromyography (EMG) of normal and affected areas is useful in differentiating neurogenic and myopathic causes.

• Nerve conduction tests measure conduction velocities in motor and sensory nerves; these should be performed when a peripheral neuropathy is suspected.

• An autopsy should be performed to discover more about the following:

  • CNS (ie, brain neuropathology)

  • Spinal cord (number and size of anterior horn cells, presence or absence of tracts at various levels)

  • Ganglia and peripheral nerves

  • Eye (ie, neuropathology)

  • Muscle tissue from different muscle groups (ie, electron microscopy and special stains)

  • Fibrous bands replacing muscle

  • Tendon attachments

  • Other visceral anomalies, malformations, deformations, and disruptions

Neurogenic types of arthrogryposis multiplex congenita

See the list below:

• Muscle fiber type predominance or disproportion is the most common neurogenic abnormality in arthrogryposis (26%). These are nonspecific alterations. Dysgenesis of the motor nuclei of the spinal cord and brainstem involves the replacement of fasciculi of muscle fibers by small muscle fibers and adipose tissue. Examples include Pierre-Robin syndrome and Möbius syndrome.

• Dysgenesis of the CNS is the second most common neurogenic abnormality in arthrogryposis (23%), with disorganization of neurons and a decrease in neurons of the cortex and motor nuclei of the brainstem and spinal cord. Clinical syndromes associated with this abnormality include trisomy 18, partial deletion of the long arm of chromosome 18 syndrome, and Zellweger syndrome.

• Dysgenesis of the anterior horn, another common neurogenic abnormality in arthrogryposis, is the cause of Meckel-Gruber syndrome and anencephaly.

• Spinal muscular atrophy (eg, Werdnig-Hoffmann disease) is another neurogenic abnormality in arthrogryposis.

Myopathic types of arthrogryposis multiplex congenita

See the list below:

• Central core disease is a form of arthrogryposis in which the central portion of each muscle fiber contains a zone in which oxidative enzyme activity is absent.

• Nemaline myopathy is indicated by abnormal threadlike structures in muscle cells. In type I nemaline myopathy, nemaline rods are present. In type II, the number of fibers with central nuclei is increased.

• Congenital muscular dystrophy is indicated by muscle fibers that demonstrate a rounded configuration and conspicuous variation in diameter. Perimysial and endomysial connective tissues are markedly increased.

• Mitochondrial cytopathy is indicated by numerous ragged-red fibers on muscle biopsy samples. It is associated with CNS abnormalities consistent with mitochondrial disease.

• Myoneural junction abnormality (eg, congenital myasthenia gravis) is another myopathic type of arthrogryposis.

Family and everyone else involved with the patient’s treatment should participate in a general management plan, with this plan involving intensive and aggressive physiotherapy, bracing, and surgical interventions.[37]  There are, however, no guidelines for the care of affected individuals.

Affected babies should be delivered in tertiary care centers.

No completely successful approach to treat arthrogryposis has been found. Goals include lower-limb alignment and establishment of stability for ambulation and upper-limb function for self-care. A literature review by Gagnon et al found that rehabilitation was the most frequently reported form of conservative treatment for arthrogryposis.[38]

Early, gentle manipulation soon after birth improves passive and active range of motion. This is especially true in the case of the inherited distal arthrogryposes, in which prolonged immobilization associated with casting may be undesirable. Late manipulation is of little value.

Early, vigorous physical therapy to stretch contractures is very important in improving joint motion and avoiding muscle atrophy. Patients with amyoplasia or distal arthrogryposis respond well to physical therapy, with excellent functional outcome. However, physical therapy may actually be harmful in patients with conditions of bony fusion such as diastrophic dysplasia, because it may lead to joint ankylosis. Recurrence of deformities following stretching is common, and surgery is often indicated.

Splinting combined with physical therapy appears preferable to continuous casting. Night splinting after surgical procedures is indicated to maintain increased range of motion.

Feeding assistance and intubation is needed in patients with severe trismus.

See Deterrence/Prevention for information on recurrence risk.

The aforementioned literature review by Gagnon et al found that osteotomy was the most common type of surgery reported for arthrogryposis.[38]

The perioperative management of the arthrogrypotic patient can be difficult and is managed by an experienced anesthesia and medical team.[39, 40, 8] The following issues are noted:

• Difficulty in venous access

• Prone to develop intraoperative hyperthermia

• Certain drugs influenced by decreased muscle mass

• Postoperatively, increased difficulty with atelectasis and stridor with an increased risk of aspiration

• Vertebral instability secondary to decreased muscle mass and high cervical hypoplasia

If surgery is contemplated, early (age 3-12 mo) one-stage (bone and tendon transfer) surgery should be performed. Fine-tuning procedures, such as opponensplasty, may improve function at a later stage.

Specific joint problems should be addressed with regard to treatment of other joints and the goals for the patient. Soft-tissue surgery should be performed early, with osteotomies carried out when growth is completed. In soft-tissue release procedures, tenotomies should be accompanied by capsulotomies. Long-term bracing and assistive devices are usually needed.

• Feet

  • The most common deformity is a rigid talipes equinovarus deformity. The goal of treatment is a plantigrade, braceable foot.

  • Casting in the first 3 months and attempting to stretch the skin often fail to correct the deformity. The patient eventually needs an extensive medial and lateral release, followed by prolonged casting and bracing.

  • Recurrence is common as the child grows, and the patient may need eventual treatment with bony procedures, such as lateral column shortenings (Lichtblau procedures) or talectomy.

  • In a skeletally mature deformed foot, triple arthrodesis often gives a satisfactory plantigrade foot. In an older child with no previous treatment, a combination of soft-tissue releases and bony procedures may be indicated.

• Knees

  • The goal of treatment is an extended knee for ambulation. This is more easily accomplished in an extension or hyperextension deformity than in a flexion deformity.

  • Flexion knee deformities are more common than fixed knee deformities and are more resistant to treatment.

  • A mild contracture (< 20°) does not interfere with functional ambulation and can be treated with passive stretching and splinting.

  • Moderate contractures (20-60°) need soft-tissue releases, including posterior capsulotomy of the knee joint, followed by long-term bracing.

  • Severe contractures (>60°) may need femoral shortening, in addition to soft-tissue releases, to decrease tension on neurovascular structures behind the knee. In an older child with severe flexion deformity, a knee disarticulation may be indicated.

  • Extension deformities often present as recurvatum or even anterior dislocation, but they respond better to physical therapy than flexion deformities. Initial treatment for recurvatum is passive stretching and splinting. If unsuccessful, quadricepsplasty should be performed when the patient is younger than 6 months. The deformity should be corrected before treating a dislocated hip to facilitate hip reduction.

• Hips

  • Hip surgery should follow foot and knee surgery, especially in the presence of knee extension deformities. Hip surgery should be performed when the patient is younger than 1 year to facilitate ambulation. In some patients with bilateral hip dislocations and extremely mobile hips, open reduction may be attempted.

  • Hip flexion contractures are more difficult to treat than dislocations. Mild hip flexion contracture is acceptable for ambulation. A flexion contracture greater than 35° requires soft-tissue releases.

  • A bilateral hip dislocation greater than 35° with flexion contracture should be treated with stretching and soft-tissue releases but not with reduction.

  • Unilateral hip dislocation requires reduction to avoid pelvic obliquity and scoliosis.

• Upper extremities

  • Treatment involves development of self-help skills (eg, feeding and toileting) and mobility skills (eg, pushing out of chair and using crutches). In evaluating the upper extremities, overall function of the entire extremity should be considered rather than function of the individual joints.

  • Upper-extremity surgery should not be considered until the patient is older than 5-6 years. Shoulder function is usually satisfactory without a rotational osteotomy unless the shoulder is severely internally rotated.

• Elbows

  • The goal of treatment is an elbow with passive or active flexion capability (feeding arm) and extension capability (toilet arm). Extension is corrected with either capsulotomy (ie, to allow passive flexion) or capsulotomy plus provision of a motor power, provided by a Steindler flexorplasty, a triceps transfer, or a pectoralis major transfer.

  • Because the elbow is crucial to hand function, the elbow must be mobile before a wrist deformity is corrected.

• Wrists

  • The major wrist deformity is flexion with ulnar deviation. Treatment should begin with stretching and splinting.

  • A severe deformity requires proximal row carpectomy with or without fusion.

  • A trapezoid wedge excision improves dorsiflexion.

• Fingers

  • Minimal to moderate flexion deformities require passive stretching and splinting.

  • More severe deformities require soft-tissue releases and often require proximal interphalangeal joint fusions.

  • Thumb-in-palm deformities need to be corrected to provide opposition-improved grasp.

• Spine

  • The spine is affected in about one third of patients. Scoliosis begins early and progresses to become a long, severe, rigid, C-shaped curve. This curve responds poorly to orthoses because it is progressive.

  • Curves greater than 35° should be treated with spinal fusion and instrumentation.

An international questionnaire study by Sawatzky et al of adults with arthrogryposis found that participants had an average over 9.8 surgeries, at least half of which were carried out during childhood. The rate of foot, knee, and hip surgeries was 78%, 45%, and 31%, respectively. A beta regression model indicated that knee and/or shoulder operations correlated negatively with adult quality of life, as measured using the Short Form 36 Health Survey Questionnaire physical capacity score (PCS), while elbow surgery correlated positively with the PCS.[41]

See the list below:

• Anesthetist

• Clinical geneticist

• Orthopedic surgeon

• Plastic surgeon

• Radiologist

• Neurologist

• Developmental pediatrician

• Pathologist

• Psychologist

• Physical and occupational therapists

• Social worker

• Educator

• Orthotist

• Rehabilitation engineer

See the list below:

• No special diet is required.

See the list below:

• Physical activity may be limited because of existing orthopedic problems. As a group, patients appear to cope well socially, participating in social activities that correspond to their needs.

• Walking is more restricted in patients with flexion contractures of the lower extremities than in those with extension contractures. Flexion contractures of the hips severely impair walking ability.

• Contracture of the elbow can cause a significant degree of disability in hand function.

• The use of crutches can be impossible for patients with upper extremity involvement associated with severe spinal deformity.

• Patients with more severe joint involvement depend on more help from other people than those with less severe joint involvement.

Drug therapy is not currently a component in the standard of care for this condition. Evidence indicates, however, that genetic mutations associated with endplate components play a role in arthrogryposis and pterygium formation. Acetylcholine treatment, together with physical therapy, seems to elicit a response from some of these pterygium syndromes, the apparent result of causing an increase in endplate function.[42]

Carefully monitor the patient, watching for postoperative complications.

Admit the patient for surgical intervention.

Patients may need to be transferred for further diagnostic evaluation and surgical intervention.

Identifying the causes of arthrogryposis remains vital for determining the management, prognosis, predicting recurrence risks and counselling couples. Early diagnosis allows for institution of appropriate investigations and offering patients informed choice including the option of termination if indicated. Multidisciplinary work by obstetricians, geneticists, neonatologists, and pediatric pathologists optimizes the chances of achieving a diagnosis and providing parents with accurate and appropriate information to enable them make informed choices with regards to their pregnancy.[43]

Recurrence risk depends on whether the contractures are extrinsically or intrinsically derived. Extrinsically derived contractures have a low recurrence risk, whereas the recurrence risk for intrinsically derived contractures depends on etiology. Arthrogryposis may be inherited in the following ways with different recurrence risks, and the patient and parents should know this information[44] :

• Autosomal dominant: Recurrence risk to offspring is 50% (eg, distal arthrogryposis).
• Autosomal recessive: Recurrence risk to offspring is 25%, and both parents are obligatory carriers (eg, lethal multiple pterygium syndrome).
• X-linked recessive: All daughters of affected males are carriers. Their sons have a 50% chance of being affected, and their daughters have a 50% chance of being carriers (eg, severe lethal, moderately severe, and resolving types of X-linked arthrogryposis).
• Multifactorial: Combined effects of multiple genes and environmental factors cause multifactorial traits. For most multifactorial diseases, empirical risks (risks based on direct observation of data) have been derived. For example, empirical recurrence risks of neural tube defects for siblings of an affected individual range from 2-5% in most populations.
• Mitochondrial: A small but significant number of diseases are caused by mitochondrial mutations. Because of the unique properties of mitochondria, these diseases display characteristic modes of inheritance (ie, inherited exclusively through the maternal line) and wide phenotypic variability. Only females can transmit the disease mutation to their offspring (eg, distal type IIB arthrogryposis).

Sporadic

For families in which a specific diagnosis cannot be made, the empiric recurrence risk to unaffected parents of an affected child, or to the affected individual with arthrogryposis, ranges from 3-5%.

The most common perioperative issues include difficulties with airway management, problematic intravenous access, and intraoperative hyperthermia.

Anesthesia can be difficult because vascular access is often restricted. Intubation may pose problems for patients with a small underdeveloped jaw, limited movement of the temporomandibular joint, or a narrow airway.[45]

Osseous hypoplasia, which is associated with decreased mechanical use in developing bone, is prone to fracture at multiple sites. Multiple perinatal fractures have been observed in osteopenic bones.

In neonates, ventilator dependence is associated with a poor prognosis. Prenatal factors that potentially predict respiratory insufficiency include decreased fetal movements, polyhydramnios, micrognathia, and thin ribs. Developmental milestones often are delayed because of limitations of movement.

Some patients develop skeletal changes secondary to the original deformities; these may include scoliosis and deformed carpal and tarsal bones, and they worsen the patient's overall condition. Limbs may undergrow after long-standing contractures. External genitalia are often abnormal (eg, cryptorchidism, absent labia majora) because of abnormal hip position.

Prognosis depends on whether defects are intrinsically or extrinsically derived. Extrinsically derived contractures carry an excellent prognosis, whereas intrinsically derived contractures carry a prognosis that depends on the etiology.

Prognosis also depends on the condition's natural history and the patient's response to therapy.

• Natural history

  • Developmental landmarks (attainment of motor, social, and language milestones)

  • Growth of affected limbs

  • Progression of contractures

  • CNS damage (lethal, stable, improving)

  • Asymmetry of contractures (improving, worsening)

  • Changes in trunk or limbs

  • Intellectual ability

  • Socialization

• Response to therapies

  • Spontaneous improvement

  • Response to physical therapy

  • Response to casting

  • Types of surgery at appropriate time

  • Development of motor strength proportionate to limb size[46]

Despite severe handicaps, the prognosis for most children with normal intelligence may be good enough to allow for independent, productive lives. However, many remain partially dependent on others, such as parents, relatives, and government subsidy. Dependency is related more closely to personality, education, and overall coping skills than to the degree of physical deformity.[47]

Properly sequenced corrective surgical procedures are required to maximize musculoskeletal function.

In addition to appropriate surgical correction, good family support, a proper educational environment, and promotion of independence at an early age are required to achieve maximal function.

A study by Nouraei et al that looked at long-term outcomes with regard to function and mobility in people with arthrogryposis found that 75% of the study’s participants lived on their own or with a partner, as opposed to with family members. The respondents, which included 177 individuals from more than 15 countries, were also almost three times more likely than the general population of the United States to possess a graduate degree. However, physical function scores were lower in persons with arthrogryposis than in the general US population, although scores were similar or greater for other quality-of-life domains of the 36-Item Short Form Health Survey (SF-36).[48]

See the list below:

• The birth of a child with arthrogryposis may be a catastrophic event for parents and family. They may experience anger, feelings of guilt, denial, disappointment, repulsion, or depression. Family members may have difficulty understanding or accepting the diagnosis, and they may have a tendency to look for magical answers. Family members may also be concerned about additional unrecognized malformations, risk of intellectual disability, and recurrence risk.

• The following up-to-date resources should be made available to families:

AVENUES

(A National Support Group for Arthrogryposis Multiplex Congenita)

PO Box 5192 Sonora, CA 95370

Phone: 209-928-3688

email: info@avenuesforamc.com

National Organization for Rare Disorders, Inc. (NORD)

55 Kenosia Avenue

PO Box 1968

Danbury, CT 06813-1968

Phone: 800-999-6673

Fax: 203-798-2291

email: orphan@rarediseases.org

NIH/National Arthritis and Musculoskeletal and Skin Disease Information Clearinghouse

One AMS Circle

Bethesda, MD 20892-3675

Phone: 301-495-4484

Shriner's Hospital for Children

Dr. Richard McCall

3100 Samford

Shreveport, LA 71103

Phone: 318-222-5704