Invitae Charcot-Marie-Tooth Disease Autosomal Recessive Panel


Test description

The Invitae Charcot-Marie-Tooth Disease Autosomal Recessive Panel analyzes up to 22 genes associated with Charcot-Marie-Tooth (CMT) disease, a hereditary neuropathy. These genes were curated based on the available evidence to date to provide a comprehensive test for genes associated with autosomal recessive CMT. Individuals with clinical signs and symptoms of CMT may benefit from diagnostic genetic testing to confirm the diagnosis, provide anticipatory guidance,help determine which relatives are at risk, or qualify affected patients to enroll in certain clinical trials.

This test covers genes associated with a recessive inheritance pattern (i.e., it is a simplex case or siblings are affected). Some clinicians may choose to order this test instead of the broader Invitae Charcot-Marie-Tooth Disease Comprehensive Panel to decrease the chance of detecting variants of uncertain significance.

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Primary panel (20 genes)


Add-on preliminary-evidence genes (2 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Alternative tests to consider

The genes on this panel can also be ordered as part of a broader panel to comprehensively test for Charcot-Marie-Tooth disease. Depending on the individual’s clinical and family history, these broader panels may be appropriate.

Charcot-Marie-Tooth (CMT) disease is a group of hereditary neuropathies characterized by progressive muscle weakness and sensory loss in the arms and legs. Individuals in the early stages of the disease often present with clumsiness due to numbness in the feet. As the disease progresses, the lack of nerve conduction to the extremities can also result in depressed tendon reflexes, muscle atrophy—especially at the ankles and hands, and foot deformities such as high, arched feet or hammertoes. Symptoms are caused by the impairment of the ability of peripheral nerves to conduct signals throughout the body, which results in reduced motor control and sensation in the arms and legs, especially at the ankles and wrists.

The majority of cases of the autosomal recessive form of CMT, CMT type 4 (CMT4), are caused by abnormalities in the myelin sheath that insulates peripheral nerve axons (demyelinating). However, some cases can also be caused by abnormalities in the peripheral nerve axons (axonal). This test is specifically for autosomal recessive subtypes of CMT (several CMT2 subtypes and various types of CMT4).

GeneSubtypeAdditional information
DNAJB2 CMT2T axonal neuropathy
EGR2 CMT1D, CMT4E demyelinating neuropathy
FGD4 CMT4H demyelinating neuropathy
FIG4 CMT4J combined axonal and demyelinating neuropathy
HINT1 neuromyotonia and axonal neuropathy axonal neuropathy
IGHMBP2 CMT2S axonal neuropathy
GDAP1 CMT2H/2K, CMT4A variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy, most common cause of recessive CMT
LMNA CMT2B1 axonal neuropathy
LRSAM1 CMT2P axonal neuropathy
MED25 CMT2B2 axonal neuropathy
MFN2 CMT2A2 axonal neuropathy
MTMR2 CMT4B1 demyelinating neuropathy
NDRG1 CMT4D demyelinating neuropathy
NEFL CMT2E, CMT1F variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy
PLEKHG5 RI-CMTC variable nerve conduction velocities, ranging from demyelinating to axonal neuropathy
PRX CMT4F demyelinating neuropathy
SBF2 CMT4B2 demyelinating neuropathy
SH3TC2 CMT4C demyelinating neuropathy
SLC25A46* CMT6B axonal neuropathy
SPG11 CMT2X axonal neuropathy
SURF1* CMT4K demyelinating neuropathy
TRIM2 CMT2R axonal neuropathy

*Preliminary-evidence genes

This multi-gene panel covers the most common genetic cause of autosomal recessive CMT, GDAP1, which accounts for ~25% of CMT4 cases. It also covers additional genes that cause rare forms of autosomal recessive CMT.

The CMT subtypes included in this test are all inherited in an autosomal recessive pattern. Some of these subtypes (EGR2, GDAP1, LMNA, LRSAM1, MFN2, NEFL) can also be inherited in an autosomal dominant pattern.

Autosomal recessive CMT is a highly penetrant condition. Individuals who have inherited a genetic variant that causes CMT are extremely likely to develop symptoms at some point in their lifetimes; however, the age of onset and the severity of symptoms are difficult to predict. Significant intra-family variability with respect to age of onset, symptoms, and disease progression has been observed.

Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system. Overall prevalence of CMT is usually reported as 1 in 2,500, although several more recent epidemiological studies reported prevalences of CMT ranging from 1 in 1,214 (in Norway) to 1 in 6,500 (in the United Kingdom). Autosomal recessive forms of CMT are rare.

Subtypes of CMT can be partially distinguished by inheritance pattern and the use of nerve conduction studies. These different subtypes can be associated with different disease severities and symptoms, but the clinical presentations vary by individual and it is difficult to distinguish the subtypes based on presentation alone. Genetic testing enables clinicians to more precisely diagnose the specific subtype of CMT.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
DNAJB2 NM_001039550.1
EGR2 NM_000399.3
FGD4 NM_139241.3
FIG4 NM_014845.5
GDAP1 NM_018972.2
HINT1 NM_005340.6
IGHMBP2 NM_002180.2
LMNA NM_170707.3
LRSAM1 NM_138361.5
MED25 NM_030973.3
MFN2 NM_014874.3
MTMR2 NM_016156.5
NDRG1 NM_006096.3
NEFL NM_006158.4
PLEKHG5 NM_020631.4
PRX NM_181882.2
SBF2 NM_030962.3
SH3TC2 NM_024577.3
SLC25A46 NM_138773.2
SPG11 NM_025137.3
SURF1 NM_003172.3
TRIM2 NM_001130067.1