Charcot-Marie-Tooth Neuropathy Type 4c
Summary
Clinical characteristics.
Charcot-Marie-Tooth neuropathy type 4C (CMT4C) is a demyelinating neuropathy characterized by early-onset severe spine deformities. The majority of affected children present with scoliosis or kyphoscoliosis between ages two and ten years, although earlier and later onset are observed. Slowly progressive neuropathy usually manifests in the first decade or adolescence, and occasionally earlier or later. Foot deformities (pes cavus, pes planus, or pes valgus) are common.
Diagnosis/testing.
Diagnosis is based on clinical findings, the results of motor nerve conduction velocity testing, and molecular genetic testing of SH3TC2, the only gene in which pathogenic variants are known to cause CMT4C. Because the diagnosis of CMT4C is defined by the presence of biallelic SH3TC2 pathogenic variants, all individuals with CMT4C have pathogenic variants in this gene.
Management.
Treatment of manifestations: Treatment of spinal deformities includes physiotherapy to preserve flexibility, bracing, and/or surgery, even at a young age. Treatment of foot deformities includes special shoes with good ankle support and/or ankle/foot orthoses (AFOs) to correct foot drop and aid walking, and in some cases surgery; associated pain and cramps may require medication.
Prevention of secondary complications: Daily heel cord stretching exercises and physical activity may help prevent contractures.
Surveillance: Monitor for onset and/or progression of scoliosis and changes in hand function and foot strength.
Agents/circumstances to avoid: Obesity; drugs and medications known to cause nerve damage (e.g., vincristine, isoniazid, taxol, cisplatin, nitrofurantoin).
Pregnancy management: Symptoms of CMT can worsen during pregnancy; some studies suggest that women with CMT require more interventions during delivery (possibly secondary to an increased incidence of abnormal fetal presentation) and may be at increased risk for postpartum bleeding.
Other: Career and employment may be influenced by hand and/or foot weakness.
Genetic counseling.
CMT4C is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for at-risk pregnancies are possible if both pathogenic variants have been identified in the family.
Diagnosis
Suggestive Findings
Charcot-Marie-Tooth neuropathy type 4C (CMT4C) should be suspected in individuals with the following clinical manifestations, nerve conduction velocities, neuropathology, and family history:
Clinical manifestations
- Early and severe scoliosis, the presenting sign in most individuals [Kessali et al 1997, Gabreëls-Festen et al 1999, Azzedine et al 2006]
- Neuropathy that usually develops in the first decade or adolescence, but occasionally manifests as delay in onset of independent ambulation in early childhood
- Slowly progressive neuropathy, with some individuals becoming wheelchair dependent because of involvement of the proximal lower limbs
Motor nerve conduction velocities (MNCV) that are in the range observed in demyelinating disease:
- MNCV of the median nerve is typically 4-37 m/sec, with a mean of 22 m/sec.
- MNCV is not correlated with disease duration.
- In some cases, electroneuromyographic examination is incomplete or does not allow measurement of MNCVs because of the severity of the secondary axonal loss.
Neuropathology. Nerve biopsies show a combination of morphologic features unique among the demyelinating forms of CMT [Kessali et al 1997, Gabreëls-Festen et al 1999, Gooding et al 2005], including the following:
- Loss of myelinated fibers
- Relatively few and small classic onion bulbs, as observed in CMT1A
- Basal membrane onion bulbs, consisting of concentric Schwann cell lamellae intermingled with single or double basal membranes or concentric basal membranes alone
- Schwann cells of unmyelinated axons, often with very thin processes and connecting links between axons
Family history consistent with autosomal recessive inheritance (includes simplex cases, i.e., a single occurrence in a family)
Establishing the Diagnosis
The diagnosis of CMT4C is established in a proband with early and severe scoliosis, slowly progressive neuropathy, slow nerve conduction velocities, and biallelic pathogenic variants in SH3TC2 (previously known as KIAA1985) [Senderek et al 2003] (see Table 1).
Molecular testing approaches can include serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing.
Serial single-gene testing can be considered based on the order in which pathogenic variants most commonly occur in individuals with the above suggestive findings:
- For simplex cases, exclusion of 17p11.2 duplication and pathogenic variants in PMP22 (CMT1A) (see CMT Overview), MPZ (CMT1B) (see CMT Overview), and GJB1, which encodes connexin 32 (CMT1X) (see CMTX)
- Sequence analysis of SH3TC2 followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found
- If molecular genetic testing does not identify biallelic SH3TC2 pathogenic variants, consideration of other demyelinating neuropathies. Of note, two (20%) of ten individuals with various neuropathies associated with pathogenic variants in EGR2 had scoliosis [Szigeti et al 2007] (see also Differential Diagnosis).
A multigene panel that includes SH3TC2 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
More comprehensive genomic testing (when available) including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if serial single-gene testing (and/or use of a multigene panel) fails to confirm a diagnosis in an individual with features of CMT4C. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Table 1.
Molecular Genetic Testing Used in Charcot-Marie-Tooth Neuropathy Type 4C
| Gene 1 | Method | Proportion of Probands with Pathogenic Variants 2 Detectable by Method |
|---|---|---|
| SH3TC2 | Sequence analysis 3 | 100% 4 |
| Gene-targeted deletion/duplication analysis 5 | None reported 6 |
- 1.
See Table A. Genes and Databases for chromosome locus and protein.
- 2.
See Molecular Genetics for information on allelic variants detected in this gene.
- 3.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
- 4.
Because this disorder is defined by the presence of biallelic pathogenic variants in the associated gene, the variant detection rate is 100% for pathogenic variants detectable through sequence analysis.
- 5.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
- 6.
No deletions or duplications involving SH3TC2 have been reported to cause Charcot-Marie-Tooth neuropathy type 4C.
Clinical Characteristics
Clinical Description
Charcot-Marie-Tooth neuropathy type 4C (CMT4C) is a demyelinating neuropathy characterized by early-onset severe scoliosis. Scoliosis as well as foot deformities were the presenting findings in most individuals with CMT4C.
Spine deformities (scoliosis or kyphoscoliosis) were observed between ages two and ten years in most cases [Kessali et al 1997, Gabreëls-Festen et al 1999], or more rarely, early in the second decade [Senderek et al 2003]. However, the disease may start at birth or much later: onset at age 37 years was reported in one individual [Colomer et al 2006].
Cumulative data indicate that scoliosis occurs in 73% of persons with CMT4C (Table 2). In some cases the spine deformities are moderate; in others they are disabling. The curvature progressed three to five degrees annually and required surgery in 7% to 39% of reported cases (Table 2) [Kessali et al 1997, Gabreëls-Festen et al 1999].
Foot deformities (pes cavus, pes planus, or pes valgus) were reported in 72% to 100% of affected individuals [Senderek et al 2003, Azzedine et al 2006, Colomer et al 2006]. Foot deformities were first observed between ages two and ten years, were moderately or severely disabling, and required surgery in 6% (1/18) to 11% (3/28) of cases (Table 2).
Table 2.
Occurrence of Manifestations of CMT4C by Study
| Study Finding | Study (Total Patients) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Azzedine et al [2006] (28) | Colomer et al [2006] (14) | Senderek et al [2003] (18) | Houlden et al [2009] (6) | Baets et al [2011] (9) | Laššuthová et al [2011] (16) | Yger et al [2012] (14) | Fischer et al [2012] (6) | Cumulative Data | ||
| Age at onset | 1st symptoms | 2-10 | 4-39 | Infancy-12 | 1-16 | <1 | 1-12 | 1-12 | ND | 1-16 |
| Neuropathy | 2-10 | Infancy-12 | 1-16 | <1 | 2-50 | 2-50 | 2-25 | 1-50 | ||
| Age at (last) exam (yrs) | 5-45 | 8-45 | 11-56 | 8-42 | ND | ND | 8-59 | 5-59 | ||
| Foot deformity | Pes cavus | 20/28 | 14/14 1 | 8/18 | Yes | ND | 13/15 | 12/14 | ND | |
| Pes planus | 7/28 | 4/18 | Yes | ND | no | no | ND | |||
| Pes valgus | 1/28 | ND | ND | ND | no | 3/14 | ND | |||
| Other | No | Hammer toes 8/18 | Small feet | ND | Hammer toes | no | ND | |||
| Total | 28/28 | 14/14 | 13/18 2 | 6/6 1 | 7/9 | 14/15 | 14/14 | ND | 96/104 (92%) | |
| Age at onset (yrs) | 2-10 | No data | 2-12 | ND | ND | ND | 1,12 3 | ND | 1-12 | |
| Surgery | 3/28 | None | 1/13 | No | ND | 9/14 | 4/14 | ND | 17/69 (24%) | |
| Spine deformity | Total | 27/28 | 5/14 4 | 11/18 4 | 6/6 | 6/9 | 10/12 | 12/12 | 5/6 | 82/105 (78%) |
| Age at onset (yrs) | 2-10 | 4 | 4-12 5 | ND | 2, 6, 7, 12 6 | ND | 7-15 | ND | 2-15 | |
| Surgery | 7 7 + 6 8 = 13/27 | 1/14 | 1/11 | 3/6 | 3/6 | ND | 1/12 | ND | 22/76 (29%) | |
ND = not done or not documented
- 1.
Authors did not specify type of deformities.
- 2.
Authors did not specify the foot deformity in the one patient who had surgery.
- 3.
Unknown for 12 of 14 patients
- 4.
Authors did not indicate whether they evaluated for kyphoscoliosis and/or lordosis.
- 5.
Onset of scoliosis in infancy; age not reported
6.Age documented in 4 patients only
- 7.
Kessali et al [1997]
- 8.
Gabreëls-Festen et al [1999]
Other. No data are available on cramps and pain in individuals with CMT4C. In general, cramps and pain are common in all forms of CMT, occurring in 56 to 96% of affected individuals, according to different studies [Carter et al 1998, Abresch et al 2002, Tiffreau et al 2006, Padua et al 2008]. Cramps are usually present from the onset, whereas pain may develop as the disease progresses.
Hypoacousis (slightly diminished auditory sensitivity) was reported in 15/103 persons with CMT4C and deafness (significant reduction of auditory sensitivity) in 12/103 persons. The cumulative data from the literature showed that hypoacousis and deafness were each present in approximately 11.5% and 14.5% of individuals, respectively (Table 3). For more detailed discussion of hearing loss in general, see Deafness and Hereditary Hearing Loss Overview.
Nystagmus was reported in 2/18 persons with CMT4C [Senderek et al 2003].
Pupillary light reflexes, facial paresis, hypoventilation/respiratory insufficiency, lingual fasciculation, head tremor, sensory ataxia, and diabetes mellitus were also reported (Table 3). The cumulative data from the literature showed that respiratory problems occurred in approximately 18% and cranial nerve involvement in 45% of individuals with CMT4C (Table 3).
Table 3.
Additional Clinical Findings in CMT4C by Study
| Clinical Finding | Study (Total Patients) | |||||||
|---|---|---|---|---|---|---|---|---|
| Azzedine et al [2006] (28) | Colomer et al [2006] (14) | Senderek et al [2003] (18) | Houlden et al [2009] (6) | Baets et al [2011] (9) | Laššuthová et al [2011] (16) | Yger et al [2012] (14) | Cumulative Data | |
| Hypoacusis | 5/28 | 0/14 | 2/18 | 0/6 | 0/9 | 0/15 | 8/13 | 15/103 |
| Deafness | 0/28 | 5/14 | 1/18 | 2/6 | 1/9 | 3/15 | 0/13 | 12/103 |
| Nystagmus | 0/28 | 0/14 | 2/18 | 0/6 | 2/9 | 0/15 | 0/13 | 4/103 |
| Pupillary light reflexes | 0/28 | 3/14 | 0/18 | 1/6 | 0/9 | 0/15 | 14/13 | 4/20 |
| Other pupillary disturbances | -- | -- | -- | Asymmetric size 1/6 | -- | -- | -- | 1/6 |
| Lingual fasciculation | -- | 3/14 | -- | -- | -- | -- | -- | 3/14 |
| Tongue atrophy and/or weakness | -- | -- | -- | 1/6 | -- | -- | 2/13 | 3/19 |
| Facial paresis | 1/28 | -- | -- | 1/6 | 1/9 | -- | 4/13 | 7/56 |
| Facial weakness | -- | -- | -- | 1/6 | -- | -- | -- | 1/6 |
| Head tremor | -- | 2/14 | -- | -- | -- | -- | -- | 2/14 |
| Vocal cord involvement | -- | -- | -- | -- | -- | -- | 1/13 | 1/13 |
| Total patients w/cranial nerve involvement | 5/28 | 9/14 | 5/14 1 | 4/6 | -- | -- | 10/13 | 33/73 |
| Respiratory insufficiency or hypoventilation | 7/28 2 | -- | 2/18 | -- | 1/9 | -- | -- | 10/55 |
| Sensory ataxia | 1/28 | 2/14 | -- | -- | -- | -- | -- | >3/42 3 |
| Diabetes mellitus | -- | -- | 1/18 | -- | -- | -- | -- | 1/18 |
| Romberg sign | -- | 2/14 | -- | -- | -- | -- | -- | 2/14 |
- 1.
14 of 18 patients were examined for cranial nerve involvement.
- 2.
Kessali et al [1997] reported that 7/11 persons required spine surgery because the severity of their deformities caused difficulty in sitting and pulmonary restriction.
- 3.
Gabreëls-Festen et al [1999] reported mild sensory ataxia in some individuals, without indicating the number of cases.
Pregnancy. See Management, Pregnancy Management.
Genotype-Phenotype Correlations
Significant intrafamilial variability in the disease course makes it difficult to identify genotype-phenotype correlations [Kessali et al 1997, Gabreëls-Festen et al 1999, Senderek et al 2003, Azzedine et al 2005a, Azzedine et al 2005b, Azzedine et al 2006].
- In 28 individuals with CMT4C, Azzedine et al [2006] found no correlation between the nature and the position of the pathogenic variant, disease duration, and the stage of disability. They also reported intrafamilial variability in age at onset, disease duration, and stage of disability.
- Colomer et al [2006] reported clinical variability in 14 affected individuals with the same pathogenic variant.
Prevalence
CMT4C (caused by biallelic pathogenic variants in SH3TC2) is a relatively frequent cause of the autosomal recessive demyelinating neuropathy CMT4. On the basis of the cumulative data, the prevalence of CMT4C among those with CMT4 is approximately 18% (53/299) [Senderek et al 2003, Azzedine et al 2006, Houlden et al 2009, Fischer et al 2012, Iguchi et al 2013]. (See CMT Overview.)
Pathogenic variants in SH3TC2 have been found in individuals of diverse geographic origins (Algeria, Morocco, France, Belgium, England, the Netherlands, Germany, Austria, Italy, Bosnia, Czech, Greece, Turkey, Iran, Japan, and Canada) and diverse ethnic origins (gypsies from Spain and Turkey) [LeGuern et al 1996, Gabreëls-Festen et al 1999, Guilbot et al 1999, Senderek et al 2003, Azzedine et al 2005a, Azzedine et al 2005b, Azzedine et al 2006, Colomer et al 2006, Houlden et al 2009, Baets et al 2011, Fischer et al 2012].
- The pathogenic variant p.Arg954Ter is recurrent in several populations, including people who originated from the Mediterranean basin, Europe, and America [Azzedine et al 2005a, Azzedine et al 2005b]. This founder effect leads to a bias in the occurrence of the disease in those populations [Azzedine et al 2005a, Azzedine et al 2005b, Gosselin et al 2008].
- Five (20%) of 25 affected individuals of Turkish origin had biallelic SH3TC2 pathogenic variants [Parman et al 2004, Fischer et al 2012].
Differential Diagnosis
See CMT Overview for discussion of approaches to diagnosis of other autosomal recessive disorders with peripheral neuropathy. Guidelines for genetic testing of individuals suspected of having a neuromuscular condition, such as CMT, have been published by Burgunder et al [2011] and Murphy et al [2012].
Baets et al [2011] reviewed the genetic spectrum of hereditary neuropathies presenting in the first year of life. Besides CMT4C, the most common disorders are the CMT4 subtypes CMT4B2 (SBF2), CMT4F (PRX), and CMT4H (FGD4). However, these subtypes occur at a low frequency compared to CMT as a whole.
CMT4A/2H is an autosomal recessive axonal, demyelinating or mixed (RI-CMTA) sensory and motor peripheral neuropathy due most often to biallelic pathogenic variants in GDAP1 [Nelis et al 2002, Birouk et al 2003, Bouhouche et al 2007]. In a few studies, single heterozygous pathogenic variants in GDAP1 were found to be inherited in an autosomal dominant manner (CMT2K) [Claramunt et al 2005]. CMT4A/2H is one of the most frequent autosomal recessive forms of CMT [Author, personal observation]. See CMT4A.
CMT1E. Autosomal recessive inheritance of severe neuropathy has also been reported with biallelic pathogenic variants in PMP22, in which heterozygous pathogenic variants typically cause the autosomal dominant CMT1 phenotype.
CMT1X, caused by hemizygous pathogenic variants in GJB1 (Cx32), is characterized by a moderate to severe motor and sensory neuropathy in affected males and usually mild to no symptoms in heterozygous females. Sensorineural deafness and central nervous system symptoms also occur in some families. Unlike CMT4C, CMT1X is inherited in an X-linked manner.
Hereditary motor and sensory neuropathy with agenesis of the corpus callosum, an autosomal recessive severe sensorimotor neuropathy with intellectual disability and agenesis of the corpus callosum has been reported in individuals from Quebec. It is caused by pathogenic variants in SLC12A6 (former names: ACCPN, KCC3), the gene encoding the K-Cl cotransporter [Howard et al 2002].
Other unclassified autosomal recessive neuropathies
- SURF1. Three individuals from consanguineous families with childhood-onset demyelinating motor/sensory neuropathy associated with nystagmus, lactic acidosis, hyperintense lesions in the putamen on T1-weighted MRI, and later development of cerebellar ataxia had deficiency of COX activity in muscle fibers associated with SURF1 homozygous or compound heterozygous pathogenic variants [Echaniz-Laguna et al 2013]. Mutation of SURF1 has also been associated with Leigh syndrome.
- TRIM2. Compound heterozygous pathogenic variants have been reported in a female with childhood-onset axonal and demyelinating neuropathy with low weight and small muscle mass [Ylikallio et al 2013]. Nerve biopsy showed enlarged myelinated fibers with increased density of neurofilaments. TRIM2 is an E3 ubiquitin ligase.
- HINT1. Loss-of-function pathogenic variants cause a motor (greater than sensory) axonal neuropathy with neuromyotonia (spontaneous high-frequency motor unit potentials on EMG) [Zimoń et al 2012]. Hahn et al [1991] described the clinical details of this disease including muscle cramping, twitching, and distal weakness.
Management
Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Charcot-Marie-Tooth neuropathy type 4C (CMT4C), the following evaluations are recommended:
- Examination by a child neurologist to evaluate for weakness and atrophy, gait stability, sensory loss, and other associated signs. It is important to distinguish between neuropathic pain and mechanical pain.
- Examination by a pediatric orthopedist to assess the amount and progression of spinal curvature and to determine the extent of foot deformities
- Examination by an otolaryngologist and/or ophthalmologist if problems with hearing or vision are present
- Consultation with a clinical geneticist and/or genetic counselor
Treatment of Manifestations
Treatment is symptomatic. Affected individuals are often managed by a multidisciplinary team that includes neurologists, physiatrists, orthopedic surgeons, and physical and occupational therapists. See Grandis & Shy [2005] for a discussion of general treatment for CMT.
Spinal deformities
- Physiotherapy helps to preserve flexibility.
- If the curvature can be reduced with bracing, either a plaster or a thermo-molded plastic corset can be used.
- If bracing and physiotherapy together are not sufficient to correct the scoliosis, surgery can be performed at an early age, even before the end of linear growth (Table 2) [Kessali et al 1997, Gabreëls-Festen et al 1999]. Surgical intervention requires consensus among the family, child (if possible), and attending physicians.
Foot deformities
- Special shoes with good ankle support and/or ankle/foot orthoses (AFOs) to correct foot drop and aid walking
- Physiotherapy to preserve flexibility
- In approximately 9% of individuals, surgery to correct severe pes cavus deformity (Table 2) [Kessali et al 1997, Guyton & Mann 2000, Colomer et al 2006]
Pain and cramps
- Neuropathic pain can be treated with antiepileptic drugs (AEDs) (e.g., pregabalin, gabapentin).
- Mechanical pain can generally be managed with a combination of physiotherapy and orthopedic treatment.
- Cramps can be controlled with quinine. However, quinine is known to induce tinnitus and reversible high-tone hearing loss.
Other
- Some individuals require forearm crutches or canes for gait stability; some need wheelchairs.
- Exercise to help the individual remain physically active according to his/her abilities is encouraged.
Prevention of Secondary Complications
Daily heel cord stretching exercises help prevent Achilles' tendon shortening.
Physical activity (e.g., swimming, bicycling, stretching) adapted to the abilities of each individual by a physiotherapist is useful to prevent contractures.
Individuals with diabetes mellitus need excellent foot care to avoid foot ulceration and necrosis.
Surveillance
Scoliosis needs to be closely followed. Monitoring four times a year is recommended.
Hand function and foot strength should be evaluated by an orthopedist every six months starting from the date of diagnosis.
Agents/Circumstances to Avoid
Obesity is to be avoided because it makes walking more difficult.
Medications which are toxic or potentially toxic to persons with CMT comprise a range of risks ranging from definite high risk to negligible risk. See the Charcot-Marie-Tooth Association website (pdf) for an up-to-date list.
Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic older and younger sibs of an affected individual in order to identify as early as possible those who would benefit from initiation of preventive measures. Evaluations can include:
- Molecular genetic testing if the pathogenic variants in the family are known;
- Consideration of motor nerve conduction velocities and nerve biopsy if the pathogenic variants in the family are not known.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
Pregnancy Management
CMT appears to be an independent risk factor for complications during pregnancy and delivery.
- The symptoms of CMT can worsen during pregnancy; in particular: cramps, subjective sensitivity (e.g., paresthesias), difficulty walking, and fatigue.
- In rare cases, crises occurring during pregnancy do not subside post partum.
- A retrospective study in Norway between 1967 and 2002 comparing 108 births to mothers with CMT with 2.1 million births to mothers without CMT determined that mothers with CMT more frequently needed interventions during delivery [Hoff et al 2005]. Bleeding post partum was also more common in mothers with CMT.
- It has been postulated that fetal presentation tends to be abnormal because of the combination of CMT in the mother and fetus [Rayl et al 1996, Hoff et al 2005].
Therapies Under Investigation
See Grandis & Shy [2005].
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder
Other
Career and employment may be influenced by persistent weakness of hands and/or feet.
Anesthesia. Relatively few studies reported in the literature address risks of anesthesia in patients with CMT. No complications were observed after anesthesia in a large cohort followed in specialized consultation, but the advice of the anesthesiologist should be followed.
- Although it had no adverse effects in 41 persons with CMT [Antognini 1992], use of succinylcholine for general anesthesia is usually contraindicated.
- Blockers of the neuromuscular junction should be used with caution.
- Local-regional anesthesia, especially epidural analgesia at child birth, has been used without problems in CMT. This use of anesthesia should be discussed on a case-by-case basis with the anesthesiologist.