Tests
1st tests to order
nerve conduction studies (NCS)
Test
This investigation should be considered for any person with a suspected neuropathy as it can confirm the diagnosis of a polyneuropathy and determine if the disorder primarily affects myelin and the Schwann cell, or the axon (i.e., whether the disorder is primarily motor, primarily sensory, or mixed). Both motor and sensory nerves should be studied, although interpretation of the results can be difficult as some types of Charcot-Marie-Tooth (CMT) disease show only slight abnormalities on NCS.
The nerve abnormalities are symmetric, with a similar degree of slowing or reduction in amplitude in all the tested nerves, and sensory nerve responses are typically absent. CMT1 is associated with demyelination and CMT2 is associated with axonal loss.
In the presence of extreme atrophy in the distal muscles, responses may not be recordable, and it may be necessary to perform the NCS at a more proximal muscle than would typically be used.
Result
conduction velocities of 15-38 m/second, reduced or absent sensory responses, and prolonged distal latencies in demyelination; reduced amplitudes and normal conduction velocities (>38m/second) in axonal loss
Tests to consider
genetic testing
Test
Persons with a family pedigree showing a dominant mutation or male-to-male transmission and signs of demyelination on nerve conduction studies (NCS) should be tested for CMT1A, the most common form of demyelinating Charcot-Marie-Tooth (CMT) disease. If there is no duplication of the PMP22 gene indicative of CMT1A, testing for other myelin gene disorders may be appropriate. If an X-linked disorder is possible, testing for CMT1X with mutations of the GJB1 gene is appropriate. A causative gene mutation is identified in approximately 80% of cases of demyelinating CMT.[17] Individuals with an axonal pattern on NCS, with or without family history, should be tested for CMT2A, the most common form of axonal CMT.[13] Only 30% to 40% of cases of axonal CMT will have an identifiable mutation. Genetic testing has more than 99% sensitivity for each subtype of CMT. Next Generation Sequencing panels will now look at 30-100 hereditary neuropathy-associated genes at one time, relatively quickly and cheaply. Exome sequencing is quickly becoming less expensive and more useful in finding new genes in CMT. If a person has negative genetic testing for the most likely known causes of CMT, it may be reasonable to send their DNA and the DNA of other affected family members' for research or clinical exome testing.
If there are existing genetic test results, do not perform repeat testing unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[18]
Result
gene mutation associated with specific CMT subtype
hip x-ray
Test
Hip x-ray should be considered in all children to screen for hip dysplasia.[14]
Result
normal or hip dysplasia
x-rays of cervical, thoracic, and lumbar spine and pelvis
Test
Spinal and pelvic x-rays should be considered for children exhibiting signs of scoliosis or kyphosis. Posteroanterior and lateral views are recommended.
Result
normal or scoliosis/kyphosis
nerve ultrasound
Test
Nerve ultrasounds may be useful for people who do not want to undergo NCS or electromyography (EMG), or if there is a question about Charcot-Marie-Tooth (CMT) versus a different neuropathy. People with CMT, particularly demyelinating forms of CMT (with CMT1A being the most well studied) will have increased nerve CSA compared to controls.[19]
Result
normal or possibly increased nerve cross sectional area (CSA) if demyelinating neuropathy
nerve biopsy
Test
Nerve biopsies may be useful if genetic testing finds one or more variants of uncertain significance in a gene that has specific microscopic nerve lesions to elucidate the pathogenicity of the variant.[20] They are also useful to distinguish between a genetic neuropathy and a nongenetic neuropathy, such as one caused by vasculitis.[21]
Result
specific genes and their corresponding nerve lesions: PMP22 (CMT1A/CMT1E): Onion bulbs; PMP22 (HNPP): Tomaculae; MPZ (CMT1B): Uncompacted Myelin, myelin out foldings, Onion bulbs; EGR2 (CMT1D): Very severe demyelination, dysmyelination, or no myelination; GJB1 (CMT1X): Clusters of regeneration; MTMR2, MTMR13, FDG4 (CMT4B1, CMT4B2, CMT4H): Myelin in- and out-foldings; SH3TC2 (CMT4C): Basal proliferation (onion bulbs), Unmyelinated fibers involvement; INF2 (CMT-DIE): Proliferation of actin filaments, Unmyelinated fibers involvement; NDRG1 (CMT4D): Adaxonal deposits; PRX (CMT4F): Abnormal paranodal loops, Dysjunction of Cajal bands; NEFL (CMT2E/CMT1F): Giant axons; MFN2 (CMT2A): Mitochondrial anomalies; GDAP1 (CMT4A): Mitochondrial anomalies; LMNA (AR-CMT2A): Severe rarefaction of large myelinated fibers, with no cluster of regeneration.
pulmonary function testing
Test
Baseline pulmonary function testing should be undertaken in the following children when they are able to complete this reliably (usually from the age of 5-6 years): children with symptoms of sleep-disordered breathing (e.g., unexplained headaches, daytime somnolence or symptoms of obstructive sleep apnea); children with recurrent lower respiratory tract infections (>2 courses of antibiotics over 4 months or >2 hospital admissions for a respiratory tract infection in 12 months); children with scoliosis (Cobb angle of >40°); all non-ambulant children.[14]
Result
normal or reduced vital capacity
Use of this content is subject to our disclaimer