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Arthrogryposis Multiplex Congenita

(Multiple Congenital Contractures)

by Simeon A. Boyadjiev Boyd, MD

Arthrogryposis multiplex congenita refers to a variety of conditions that involve congenital limitation of joint movement. Intelligence is relatively normal except when the arthrogryposis is caused by a disorder or syndrome that also affects intelligence.

Arthrogryposis is not a specific diagnosis but rather a clinical finding of congenital contractures; these may be present in > 300 different disorders. Prevalence varies in different studies between about 1/3,000 to 1/12,000 live births. The perinatal mortality for some of the underlying conditions is as high as 32%, so establishing a specific diagnosis is important for prognosis and genetic counseling.

There are two major types of arthrogryposis multiplex congenita (AMC):

  • Amyoplasia (classic arthrogryposis): Multiple symmetric contractures occur in the limbs. Affected muscles are hypoplastic and have fibrous and fatty degeneration. Usually intelligence is normal. About 10% of patients have abdominal abnormalities (eg, gastroschisis, bowel atresia) due to a lack of muscle formation. Nearly all cases are sporadic.

  • Distal arthrogryposis : The hands and feet are involved, but the large joints are typically spared. Distal arthrogryposes are a heterogeneous group of disorders, many of which are associated with a specific gene defect in one of a number of genes that encode components of the contractile apparatus. Many distal arthrogryposes are transmitted as autosomal dominant disorders, but x-linked mutations are known.

Etiology

Any condition that impairs in utero movement for > 3 wk can result in AMC. Causes may involve

  • Physical limitation of movement (eg, due to uterine malformations, multiple gestations, or oligohydramnios) causing fetal akinesia/hypokinesia syndrome (Pena-Shokeir syndrome), frequently associated with pulmonary hypoplasia

  • Maternal disorders (eg, multiple sclerosis, impaired uterine vascularity)

  • Genetic disorders affecting the fetus (eg, neuropathies; myopathies, including muscular dystrophies; connective tissue abnormalities; impaired fetal vascularity; anterior horn cell disease)

More than 35 specific genetic disorders (eg, spinal muscular atrophy type I, trisomy 18) have been linked to AMC.

Symptoms and Signs

Deformities are prominent at birth. AMC is not progressive; however, the condition that causes it (eg, muscular dystrophy) may be. Affected joints are contracted in flexion or extension. In the classic manifestations of AMC, shoulders are sloped, adducted, and internally rotated, the elbows are extended, and the wrists and digits are flexed. Hips may be dislocated and are usually slightly flexed. Knees are extended; feet are often in the equinovarus position. Leg muscles are usually hypoplastic, and limbs tend to be tubular and featureless. Soft-tissue webbing sometimes occurs over ventral aspects of the flexed joints. The spine may be scoliotic. Except for slenderness of the long bones, the skeleton appears normal on x-rays. Physical disabilities may be severe. As noted, some children may have primary CNS dysfunction, but intelligence is usually unimpaired.

Endotracheal intubation during surgery may be difficult because children have small immobile jaws. Other abnormalities that rarely accompany arthrogryposis include microcephaly, cleft palate, cryptorchidism, and cardiac and urinary tract abnormalities; these findings raise suspicion for an underlying chromosomal defect or genetic syndrome.

Diagnosis

  • Clinical evaluation

  • Testing for cause

If a newborn has multiple contractures, the initial evaluation should determine whether the condition is amyoplasia, distal arthrogryposis, or another syndrome where multiple contractures are associated with unrelated congenital anomalies and/or metabolic disorders. When available, a clinical geneticist should coordinate the assessment and management; typically, practitioners from many specialties are involved. A syndromic form of AMC is suspected when developmental delays and/or other congenital anomalies are present, and such patients should be evaluated for CNS disorders and monitored for progressive neurologic symptoms.

Evaluation should also include a thorough assessment for associated physical, chromosomal, and genetic abnormalities. Specific disorders to be sought include Freeman-Sheldon syndrome, Holt-Oram syndrome, Larsen syndrome, Miller syndrome, multiple pterygium syndrome, and DiGeorge syndrome (22q11 deletion syndrome). Testing typically starts with a chromosomal microarray analysis and followed by specific gene tests that are done individually or as a standard panel by many genetic laboratories. Electromyography and muscle biopsy are useful to diagnose neuropathic and myopathic disorders. In classic AMC, muscle biopsy typically shows amyoplasia, with fatty and fibrous replacement of tissues.

Treatment

  • Joint manipulation and casting

  • Sometimes surgical procedures

Early orthopedic and physical therapy evaluations are indicated. Joint manipulation and casting during the first few months of life may produce considerable improvement. Orthotics may help. Surgery may be needed later to align the angle of ankylosis, but mobility is rarely enhanced. Muscle transfers (eg, surgically moving the triceps so that it can flex the elbow) may improve function. Many children do remarkably well; two thirds are ambulatory after treatment.

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