(See also Introduction to Congenital Craniofacial and Musculoskeletal Abnormalities Introduction to Congenital Craniofacial and Musculoskeletal Abnormalities Craniofacial and musculoskeletal abnormalities are common among children. They may involve only a single, specific site (eg, cleft lip, cleft palate, clubfoot) or be part of a syndrome of multiple... read more .)
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 Gastroschisis Gastroschisis is protrusion of the abdominal viscera through a full-thickness abdominal wall defect, usually to the right of the umbilical cord insertion. (See also Overview of Congenital Gastrointestinal... read more , 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.
Any condition that impairs in utero movement for > 3 weeks can result in AMC. Causes may involve
Physical limitation of movement (eg, due to uterine malformations, multiple gestations, or oligohydramnios Oligohydramnios Oligohydramnios is a deficient volume of amniotic fluid; it is associated with maternal and fetal complications. Diagnosis is by ultrasonographic measurement of amniotic fluid volume. Management... read more ) causing fetal akinesia/hypokinesia syndrome (Pena-Shokeir syndrome), frequently associated with pulmonary hypoplasia
Maternal disorders (eg, multiple sclerosis Multiple Sclerosis (MS) Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness... read more , impaired uterine vascularity)
Genetic disorders affecting the fetus (eg, neuropathies; myopathies Congenital Myopathies Congenital myopathy is a term sometimes applied to hundreds of distinct neuromuscular disorders that may be present at birth, but it is usually reserved for a group of rare, inherited, primary... read more , including muscular dystrophies Introduction to Inherited Muscular Disorders Muscular dystrophies are inherited, progressive muscle disorders resulting from defects in one or more genes needed for normal muscle structure and function; dystrophic changes (eg, muscle fiber... read more ; connective tissue abnormalities Introduction to Connective Tissue Disorders in Children There are over 200 disorders that involve connective tissue. Certain disorders are characterized by overactivity of the immune system with resulting inflammation and systemic damage to the tissues... read more ; impaired fetal vascularity; anterior horn cell disease)
More than 35 specific genetic disorders (eg, spinal muscular atrophy type I, trisomy 18 Trisomy 18 Trisomy 18 is caused by an extra chromosome 18 and is usually associated with intellectual disability, small birth size, and various congenital anomalies, including severe microcephaly, heart... read more ) 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 central nervous system 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.
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 central nervous system 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 followed by specific gene tests that are done individually or as a standard panel by many genetic laboratories (1 Diagnosis references Arthrogryposis multiplex congenita refers to a variety of conditions that involve congenital limitation of joint movement. Intelligence is typically normal except when the arthrogryposis is... read more ). 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.
Whole exome sequencing should be considered when other tests do not yield a definitive diagnosis, especially in familial cases (2 Diagnosis references Arthrogryposis multiplex congenita refers to a variety of conditions that involve congenital limitation of joint movement. Intelligence is typically normal except when the arthrogryposis is... read more ).
1. Todd EJ, Yau KS, Ong R, et al: Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth. Orphanet J Rare Dis 10:148, 2015. doi: 10.1186/s13023-015-0364-0.
2. Hunter JM, Ahearn ME, Balak CD, et al: Novel pathogenic variants and genes for myopathies identified by whole exome sequencing. Mol Genet Genomic Med 3(4):283–301, 2015. doi: 10.1002/mgg3.142.
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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