Rehabilitation Program

Physical Therapy

Daily heel-cord stretching exercises are desirable to prevent Achilles tendon shortening. Special shoes with good ankle support may be needed. Physical therapy can assist with ambulation and provide necessary evaluation and training with orthoses, such as an ankle-foot orthosis (AFO).^{[11, 72]}

Patients often require an AFO to correct foot drop and to aid walking.^[73]It is important to address the biomechanical needs of a CMT patient, since there may be bilateral strength differences due to progression of the disease. Optimizing the mechanical characteristics of the AFO to patient needs can be challenging. One strategy is to design AFOs of varying stiffness and allow patients to experience range energy storage and release characteristics prior to selecting the stiffness they prefer.

Patients with CMT discard AFOs because they highlight their disability, are not essential for their limited daily walking, and are uncomfortable. Prescription of AFOs should be accompanied by psychological support, with note made that research into more comfortable and cosmetically acceptable solutions for the problem of footdrop in CMT is ongoing.^[74]

In an email survey by Zuccarino et al regarding AFO satisfaction in persons with CMT, more than one third of participants responded negatively, with patients disliking the appearance of AFOs and suffering from discomfort, abrasions or irritation, and pain.^[75]

Custom carbon-fiber composite AFOs have been reported to improve gait of CMT patients^[76]AFO prescription appears relevant for improving balance and gait performance in CMT patients, particularly when the model adequately compensates for specific muscle deficits. Custom polypropylene AFOs have shown to improve walking speed and gait parameters in patients with CMT.^{[77, 78]}

Transcutaneous electrical nerve stimulator (TENS) units can be used to improve muscle functions in patients with CMT.^[12]

Some patients require the use of forearm crutches or a cane for improved gait stability, but fewer than 5% of patients need wheelchairs. Advise patients with Charcot-Marie-Tooth disease (CMT) about weight management, because obesity makes ambulation more difficult. Encourage exercise within each individual patient's capability.^[79]Most patients with CMT usually remain physically active.

A literature review by Sman et al suggested that even though studies have shown exercise-related strength and function changes in patients with CMT, these results should be considered cautiously, since few such studies are available and their quality of evidence is only moderate.^[80]

A multicenter, prospective, randomized, single-blind, controlled study by Mori et al of patients with CMT-1A found that an objective benefit could be obtained from stretching and proprioceptive exercise and from treadmill training. Moreover, this could be accomplished without overwork weakness, with the investigators also reporting a low dropout rate and no deterioration in motor performance.^[81]

Occupational Therapy

An occupational therapist may recommend the use of adaptive equipment for activities of daily living (ADL) and self-care. Fitting of a proper orthosis and keeping the wrist and hand in functional position may be required. Vocational and avocational training regarding the importance of career and employment implications may be needed because of persistent weakness of the hands and/or feet.^{[36, 37]}

Medical Issues/Complications

In Charcot-Marie-Tooth disease (CMT), no treatment currently exists to reverse or slow the natural disease process for the underlying disorder. Nothing can correct the abnormal myelin, prevent the myelin's degeneration, or prevent axonal degeneration.

Stem-cell and gene-transfer therapies are the most promising forms of treatment for the cure of CMT.^[82]Some promising results have been reported for antiprogesterone therapy and ascorbic acid treatment for CMT-1A in animal CMT-1A models. Progesterone-receptor antagonists have reduced PMP-22 overexpression and clinical severity in a CMT-1A rat model. Furthermore, ascorbic acid treatment reduced premature death and demyelination in a CMT-1A mouse model. (A literature review by Gess et al, however, suggested that ascorbic acid does not improve outcomes in adults with CMT-1A, as measured by the neuropathy score at 12 months.^[83]) There is also the prospect of developing drugs to reduce the effects of PMP-22 overexpression in gene duplications by down-regulation via the promoter. Improved understanding of the genetics and biochemistry of the disorder offers hope for an eventual treatment.

Charcot-Marie-Tooth disease increases the risk for complications during delivery, which is linked to a higher occurrence of emergency interventions during birth.^[84]

Patients often are evaluated and managed symptomatically by a team that includes a physiatrist, a neurologist, an orthopedic surgeon, and physical and occupational therapists.

Surgical Intervention

Orthopedic surgery may be required to correct severe pes cavus deformities, scoliosis, and other joint deformities.^{[13, 14, 15]}

Consultations

Consult a specialist in neurogenetics to order specific genetic tests and proper genetic counseling.

Medication

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Media Gallery

Foot deformities in a 16-year-old boy with Charcot-Marie-Tooth disease type 1A.
Charcot-Marie-Tooth disease type 1A DNA test showing duplication in the short arm of chromosome 17 (A) compared with normal (B).
Nerve conduction study showing decreased nerve conduction velocity in the median nerve in an 18-year-old woman with Charcot-Marie-Tooth disease type 1.
Foot of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.
Hands of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.
Right ulnar motor nerve conduction study in a 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.
Left ulnar motor nerve conduction study in 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.

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Table. Charcot-Marie-Tooth Disorders: Genetic and Clinical Feature Comparison

Table. Charcot-Marie-Tooth Disorders: Genetic and Clinical Feature Comparison

CMT Type	Chromosome; Inheritance Pattern	Age of Onset	Clinical Features	Average NCVs^§
CMT-1A (PMP-22^¶ dupl.)	17p11.2; AD*	First decade	Distal weakness	15-20 m/s
CMT-1B (P₀ -MPZ)**	1q23.3; AD	First decade	Distal weakness	< 20 m/s
CMT-1C (non-A, non-B) (LITAF)	16p13.13;AD	Second decade	Distal weakness	26-42 m/s
CMT-1D (EGR-2)^#	10q21.3; AD	First decade	Distal weakness	15-20 m/s
CMT-1E (PMP22)	17p11.2; AD	First decade	Distal weakness, deafness	15-20 m/s
CMT-1F (NEFL)	8p21.2; AD	First decade	Distal weakness	15-20 m/s
CMT-X (connexin-32)^{[51, 52, 53, 54]}	Xq13; XD^‡	Second decade	Distal weakness	25-40 m/s
CMT-2A	1p36; AD	10 y	Distal weakness	>38 m/s
CMT-2B	3q21; AD	Second decade	Distal weakness, sensory loss, skin ulcers	Axon loss; Normal
CMT-2C	12q23-q24, AD	First decade	Vocal cord, diaphragm, and distal weakness	>50 m/s
CMT-2D	7p14; AD	16-30 y	Distal weakness, upper limb predominantly	Axon loss; N^††
CMT-2E	8p21; AD	10-30 y	Distal weakness, lower limb predominantly	Axon loss; N
CMT-2F	7q11-q21; AD	15-25 y	Distal weakness	Axon loss; N
CMT-2G	12q12-q13; AD	9-76 y	Distal weakness	Axon loss; N
CMT-2H	8q21; AD	15-25 y	Distal weakness, pyramidal features	Axon loss; N
CMT-2I	1q23; AD	47-60 y	Distal weakness	Axon loss; N
CMT-2J	1q23; AD	40-50 y	Distal weakness, hearing loss	Axon loss; N
CMT-2K	8q13-q21; AD	< 4 y	Distal weakness	Axon loss; N
CMT-2L	12q24; AD	15-25 y	Distal weakness	Axon loss; N
CMT–R-Ax (Ouvrier)	AR	First decade	Distal weakness	Axon loss; N
CMT–R-Ax (Moroccan)	1q21; AR	Second decade	Distal weakness	Axon loss; N
Cowchock syndrome	Xq24-q26	First decade	Distal weakness, deafness, mental retardation	Axon loss; N
HNPP^\|\| (PMP-22 deletion)^[55] or tomaculous neuropathy	17p11; AD	All ages	Episodic weakness and numbness	Conduction Blocks
Dejerine-Sottas-syndrome (DSS) or HMSN-3^[56]	P₀; AR PMP-22; AD 8q23; AD	2 y	Severe weakness	< 10 m/s
Congenital hypomyelination (CH)	P₀, EGR-2 or PMP-22 AR	Birth	Severe weakness	< 10 m/s
CMT-4A^[57]	8q13; AR	Childhood	Distal weakness	Slow
CMT-4B (myotubularin- related protein 2)^{[58, 59]}	11q23; AR	2-4 y	Distal and proximal weakness	Slow
CMT-4C	5q23; AR	5-15 y	Delayed walking	14-32 m/s
CMT-4D (Lom) (N-myc downstream- regulated gene 1)	8q24; AR	1-10 y	Distal muscle wasting, foot and hand deformities	10-20 m/s
CMT-4E (EGR-2)	10q21; AR	Birth	Infant hypotonia	9-20 m/s
CMT-4G	10q23.2; AR	8-16 years	Distal weakness	9-20 m/s
CMT-4H	12p11.21-q13.11; AR	0-2 years	Delayed walking	9-20 m/s
CMT-4F	19q13; AR	1-3 y	Motor delay	Absent
Autosomal dominant †Autosomal recessive ‡X-linked dominant §Nerve conduction velocities \|\|Hereditary neuropathy with liability to pressure palsy ¶Peripheral myelin protein #Early growth response *Myelin protein zero ††Normal