Arthrogryposis Workup

Updated: Aug 30, 2021
  • Author: Mithilesh Kumar Lal, MD, MBBS, MRCP, FRCPCH, MRCPCH(UK); Chief Editor: Maria Descartes, MD  more...
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Laboratory Studies

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.


Imaging Studies

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.


Other Tests

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


Histologic Findings

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.