Congenital Myopathies Workup

Updated: Mar 11, 2019
  • Author: Matthew Harmelink, MD; Chief Editor: Amy Kao, MD  more...
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Approach Considerations

In the evaluation of a patient with possible congenital myopathy, consideration of the pattern of clinical phenotype, laboratory examination, and electrodiagnostic studies are the first line of evaluations to ensure that patients clinically fit. 

However, phenotypic correlation with a genetically congruent mutations is the gold standard for diagnosis. At times, however, a definitive gene is not able to be identified. In these cases, returning to muscle biopsy findings can help confirm the diagnosis based upon the known histopathologic features.

Initially, as with any child or person with weakness, localization by history and examination to a peripheral cause is prudent. Subsequently, biochemical evaluation with a creatine kinase can rapidly help narrow the differential. Significantly elelvated creatine kinase levels (>5 times the upper range of normal) is unlikely to be a congenital myopathy and other diseases such as the muscular dystrophies should be considered. However, in infants, be catious that early testing after birth (within a few days to a week) can demonstrate a falsely elevated level from baseline and may need to be rechecked.

Subsequently, electrodiagnostic evaluation can be helpful in determining neurogenci from myopathic disease in an infant and further narrow the differential. This allows the provider to proceed with genetic testing and/or muscle biopsy for further evaluation.

In previously diagnosed patients, a multidisciplinary approach is warranted given the complex care of these patients.


Laboratory Studies

Creatine kinase

Creatine kinase (CK) level is typically either normal or mildly elevated (2–5 times the normal range) in all of the congenital myopathies. There is some suggestion that more moderately elevated levels can be seen in central core disease as well as asymptomatic carriers of the ryanodine receptor mutation in CCD.

If the CK level is very high (>5 times the upper limit of normal), this is suggestive of a muscular dystrophy.


Other Tests

Electromyography (EMG) and nerve conduction studies (NCS)

These studies test the electrical patterns of muscles and nerves. They can help to confirm the diagnosis, but results from these tests can be normal in a patient with congenital myopathy.  

The greatest value of EMG/NCS is to help exclude other causes of congenital myopathy. As such, these tests should be considered prior to a more costly, and invasive, muscle biopsy or focused genetic testing. EMG/NCS should be considered in all cases of congenital myopathy given that creatine kinase level is not typically suggestive of a muscle disease given its typically normal range of values.

In congenital myopathy, NCS findings can be normal or demonstrate low-amplitude responses in the motor nerve conduction studies in severe cases, while the EMG findings are either normal or show the typical small-amplitude, narrow-duration motor unit potentials (MUPs) that are seen in myopathies. Fibrillations and positive sharp waves are rare except in the more severe phenotypes.

Electrocardiography (ECG) and echocardiogram

Cardiac disease may be prominent in nemaline myopathy or, at times, in other congenital myopathies. Obtain an ECG when considering these diagnoses. Unless there are clinical symptoms, this testing is typically done after genetic or pathologic confirmation.

Pulmonary function studies/sleep studies

With the common respiratory weakness, evaluation for pulmonary function in appropriately aged patients is often warranted. The relationship to skeletal muscle weakness and respiratory weakness varies by the underlying disorder. As such, one should use symptology and genotype rather than muscle strength to direct when to obtain testing. Additionally, nocturnal hypoventilation often preceeds daytime symptoms but can be missed in a clinical encounter without directed questioning of patients.



Muscle biopsy

The utility of muscle biopsy has changed significantly over the past few decades. While traditionally the muscle biopsy would be an early step, and conducted prior to genetic testing, this trend is changing. With the cheaper, more rapid turnaround of genetic testing, looking to genotyping patients as first-line evaluations in patients who are not critically ill can be considered.

In critically ill neonates, a muscle biopsy may provide a category of disease as well as give some indication of severity based upon histopathologic features. However, genetic identification remains the ideal standard to allow for further counseling.

The biopsy should be conducted in a muscle that is weak but that retains bulk and some strength. Typically, the vastus lateralis remains an ideal muscle of choice. The evaluation should be undertaken at a facility skilled with both procuring, processing, and evaluating muscle biopsies given technical aspects can limit interpretation. Additionally, availability of muscle-specific testing and electron microspcopy can be helpful in diagnosis.

Finally, in infants and neonates who have mild symptoms, an early biopsy may be normal and need to be repeated years later after the pathologic features have been able to develop.


Imaging Studies

Muscle imaging is not typically performed in congenital myopathies.