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Charcot-Marie-Tooth Disease in a High School Tennis Player

Teresa S. Stadler, MD
David Ross, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 30 - NO. 10 - OCTOBER 2002


In Brief: A high school tennis player had recurrent ankle sprains that were initially attributed to incomplete rehabilitation. A closer look revealed subtle symptoms of Charcot-Marie-Tooth disease (CMT), a common, inherited neuromuscular disorder. This case underscores the importance of a wide differential diagnosis when encountering recurrent conditions. Early diagnosis of CMT is imperative so that appropriate injury-prevention measures can be taken.

The underlying cause of recurrent ankle sprains may be improper rehabilitation; however, other, less apparent, conditions may be the source. A comprehensive history and physical examination may lead to the diagnosis of Charcot-Marie-Tooth (CMT) disease, as in the following case. Awareness of this fairly common condition may lead to early diagnosis and prevent recurrent ankle injuries in an otherwise healthy patient.

Case Report

A 16-year-old male varsity tennis player came to our sports medicine clinic with persistent right ankle pain 2 days after he had an inversion injury while sidestepping in a tennis match. He was able to walk off the court but was not able to continue playing that day. The ankle did not swell.

History. The patient had a history of ankle sprains, usually related to tennis or running, occurring five to eight times per year in the previous 4 years. He had been playing tennis competitively for 8 years.

In the previous 3 years, he had been evaluated by two family medicine physicians, a podiatrist, and an orthopedist. On each of these occasions, the diagnosis was ankle sprain. Conservative treatment and physical therapy were recommended. Each time, the patient complied with physical therapy recommendations for only 1 to 2 weeks. Most of his sprains were treated at home with relative rest, ice, compression, and elevation for a few days. He was usually pain free and able to return to play in 4 to 5 days.

His medical and surgical history were unremarkable. Both parents and all grandparents are living and well. He has one 15-year-old brother who had recently been put in "special education" for hand weakness that makes him write very slowly. No family history of foot or ankle problems exists. The patient had no known drug allergies and denied the use of tobacco, alcohol, or recreational drugs. He and his parents were unaware of any exposure to chemicals or toxic agents.

Physical exam. Physical examination was positive for a mild reduction of muscle volume in his hands and a significant reduction of muscle volume in his feet and lower legs. Maximal circumference at the calf was 38.5 cm, and minimal circumference just above the maleoli was 19.5 cm, bilaterally. Marked pes cavus (figure 1) and hammertoes of the third and fourth digits were seen bilaterally (figure 2). Mild tenderness to palpation was noted only over the right anterior talofibular ligament.

Review of systems was positive only for hand tremor at rest. Ligamentous testing revealed that the anterior drawer was 2+ and talar tilt was 1+ bilaterally. Proximal tibiofibular compression did not produce ankle pain. Flexibility testing with the sit-and-reach test was 30 cm from the third fingertip to the wall. The patient's gait demonstrated bilateral foot drop.

His range of motion and strength were normal for ankle plantar flexion and inversion and for great toe flexion bilaterally. The patient was unable to actively dorsiflex the ankles or extend the great toe on either foot. Passively, he could obtain 10° of dorsiflexion and great toe extension bilaterally. Active eversion was decreased at 10° on both ankles (see figure 2). Eversion strength testing was stage 1/5 (muscle flicker but no movement) on both sides. The patient could walk on the balls of his feet without difficulty; however, he was unable to walk on his heels.

His upper- and lower-extremity sensation was intact to pinprick, light touch, vibration, and temperature. Deep tendon reflexes and pulses were normal. Proprioception testing revealed that he could balance with eyes closed for 7 seconds on the right foot and 1 second on the left foot.

Based on his history and physical exam, an underlying neuromuscular disease was suspected for the recurrent ankle sprains. The patient was referred to a neurologist for further evaluation. The differential diagnosis included spinal stenosis, motor neuron diseases, CMT disease, lead or mercury toxicity, and amyloidosis.

Lab tests. Laboratory studies for complete blood count, electrolytes, renal function, liver function, and vitamin B12 and folate levels were normal. No variants of hemoglobin were noted. Testing for lead, mercury, and ceruloplasmin levels showed no significant abnormalities. Nerve conduction studies revealed peripheral sensorimotor slowing that was worse in the lower extremities than in the upper extremities. An electromyogram showed chronic reinnervation changes. Genetic testing was negative for CMT type 1 (CMT1) and subtypes X1 and 1B. No test for CMT type 2 (CMT2) is available; therefore, genetic tests would not have detected nor ruled out CMT2 in the differential diagnosis.

Diagnosis. Based on clinical presentation and electrodiagnostic studies, the patient was diagnosed as having CMT2. On examination, the patient's brother had marked upper-extremity weakness, marked pes cavus, and hammertoes. Subsequent workup of the patient's brother also led to the diagnosis of CMT2.

Treatment and follow-up. Ankle-foot orthoses, aggressive physical therapy for strength and proprioception, and continued moderate activity were recommended. The patient complied with our recommendations for physical therapy, but he did not want to try orthoses. He continues to play tennis four times per week. In the 10 months since he began vigorous rehabilitation, he has had only one ankle sprain.

More About CMT

CMT, the most common inherited neurologic disorder, affects 1 in 2,000 people worldwide.1,2 It is just as common as multiple sclerosis or amyotropic lateral sclerosis (Lou Gehrig's disease), but it is usually not life-threatening.3 Progressive weakness and sensory deficits are noted first in the feet and legs. Upper-extremity findings generally appear later in the clinical course of disease or may not appear at all. CMT does not affect lifespan or intellectual function and is not associated with any systemic disorder.

Peroneal weakness may be the earliest finding. Such weakness allows for frequent ankle inversion injuries that result in chronically lax ligaments. CMT has been called peroneal muscular atrophy because of the early effect on peroneal muscles. A third, more recent name—hereditary motor and sensory neuropathy—has many overlapping and poorly defined subdivisions.2 Multiple detailed classifications, based on mode of inheritance, exist as well.4

Subtle indications. At initial presentation, the typical CMT patient is 12 to 20 years old and complains of frequent tripping over carpets or objects when a dropped foot gets caught during the swing phase of gait. A parent may have noticed a change in gait, such as raising knees unusually high to compensate for foot drop. Patients should be asked about problems with walking, running, and balance. Patients who have CMT usually do not report tremor; however, when specifically asked, about 40% of patients will respond affirmatively.5

The patient may have a history of loss of balance or strength, frequent tripping, and ankle sprains. Several doctors may already have seen them. Because CMT may be exacerbated by high doses of several medicines (table 1), history taking should include all medications.3

TABLE 1. Drugs That May Be Toxic to Patients
Who Have Charcot-Marie-Tooth Disease

Drugs That Are Contraindicated

Alcohol
Amiodarone hydrochloride
Chloramphenicol palmitate
Chloramphenicol sodium succinate
Cis-platinum, cisplatin
Dapsone
Diphenylhydantoin
Disulfiram
Doxorubicin hydrochloride
Glutethimide
Gold sodium thiomalate
Hydralazine hydrochloride
Isoniazid
Megadoses* of vitamin A, D, & B6 (pyridoxine)
Metronidazole
Nitrofurantoin monohydrate
Nitrous oxide (chronic repeated inhalation)
Paclitaxel
Penicillin (large intravenous doses)
Perhexiline maleate
Vincristine sulfate

Drugs That Should Be Used With Caution

Lithium carbonate
Lithium citrate
Misonidazole
Selective serotonin-reuptake inhibitor antidepressants (SSRIs)†


*Megadose is defined as 10 times the dietary recommended allowance.
†Warning: Combining SSRIs and over-the-counter cold remedies can cause excessive serotonergic activity and a possibly fatal reaction.
Table adapted with permission from the Charcot-Marie-Tooth Association.3

Looking for signs. The physical signs of the lower extremity include pes cavus, hammertoes, corns over plantar metatarsal heads, and decreased vibration sensation in the stocking distribution. Bilateral pes cavovarus is the most common pathologic foot deformity seen.2 Deep tendon reflexes are normal in the early stages of CMT. Stance and gait should be evaluated with the patient barefoot. Marked pes cavus is apparent early in the disease. The earliest objective gait abnormality is the inability to walk on the heels. Lower-leg atrophy results in the classic "inverted champagne bottle" appearance.

Areflexia is usually seen first in the ankle and progresses to the patella and finally to the upper extremity. If the disease affects the upper extremities, the patient may exhibit weakness and atrophy of intrinsic muscles of the hand, especially the thenar eminence. The patient may report difficulty using shirt buttons, zippers, utensils, or writing with a pencil. A complete physical and neurologic examination should be performed, focusing on peripheral motor and sensory deficits.

Genetics. CMT includes two main subtypes: CMT1 (demyelinating) and CMT2 (axonal).6 It is inherited in an autosomal-dominant (CMT1 and possibly CMT2), recessive, or X-linked fashion (CMTX1); autosomal dominant is the most common form.7 Several genes are known to be responsible for CMT1, but the specific genes that cause CMT2 are still being described. DNA testing is available for CMT1 and subtypes X1 and 1B, but not for CMT2; therefore, diagnosis of CMT2 is based on clinical presentation and electrodiagnostic studies, as in this case report. A more detailed discussion of the mechanisms of CMT inheritance is a current research topic beyond the scope of this article.

Genetic expression of CMT is highly variable, and generation skipping is not uncommon. Family history is positive in only 65% of cases.8 The degree of severity varies among patients and even within the same family. Clinical expression is complete by the time the patient is 30 years old. Patients who have CMT2 generally have a later onset than those who have CMT1 but are more likely to have an affected relative. To determine the pattern of inheritance, consultation with a genetic counselor may be necessary.

Many patients are surprised by their diagnosis even though CMT may have been in their family for generations. In our patient, the extended family history was initially negative. It was not until his fourth office visit that repeated questioning revealed that his 15-year-old brother had upper-extremity peripheral weakness.

Although the condition had gone undiagnosed for 3 years, our patient found the CMT2 diagnosis helpful. He was relieved to know he wasn't "just clumsy." Because the disease often develops between the ages of 12 and 20, self-esteem issues, depression, and feelings of failure are common. We discussed psychological counseling, but our patient did not pursue it. He felt that physical therapy made him stronger, and that this in turn made him mentally stronger.

Diagnosis. Strict clinical criteria for the diagnosis of CMT are nonexistent. Instead, diagnosis is based on findings of pes cavus, slowed nerve conduction velocities, and peripheral weakness, particularly of the anterior and lateral leg.9-11 Our patient met these criteria.

Treatment. No cure or quick palliative treatment is available for CMT. Physical therapy and moderate activity are recommended to maintain strength, endurance, and balance.7 Gait training, with or without leg braces, may help reduce the energy expenditure of walking.3 Ankle sprains may be lessened in severity and frequency with stirrup braces or splints, orthoses, or custom shoes. Patients who have CMT should understand the medications they are taking and be given a list of medications that worsen their condition.4 This list should be shared with all treating physicians.

Surgical correction of foot and toe deformities may be helpful as a last resort. Flexion deformity, early soft-tissue release, and tendon transfers may help prevent or delay more extensive bony procedures.2 Because CMT is progressive, an initially good surgical result may deteriorate with changing motor function.9

Preventing Injury

CMT is not currently preventable. Early diagnosis may help other family members as well as the patient. By beginning physical therapy for strength and proprioception as soon as possible, the physician may spare the patient needless pain from sprains or falls. Orthoses and ankle braces may also be helpful.

References

  1. Marti RK, van Dijk N: Ankle sprains, in Baker CL Jr, Flandry F, Henderson JM (eds): The Hughston Clinic Sports Medicine Book. Baltimore, Williams & Wilkins, 1995, p 586
  2. Holmes JR, Hansen ST Jr: Foot and ankle manifestations of Charcot-Marie-Tooth disease. Foot Ankle 1993;14(8):476-486
  3. The Charcot-Marie-Tooth Association: Medical Alert page. Available at https://www.charcot-marie-tooth.org. Accessed August 21, 2002
  4. De Jonghe P, Timmerman V, Nelis E, et al: Charcot-Marie-Tooth disease and related peripheral neuropathies. J Peripher Nerv Syst 1997;2(4)370-387
  5. Cardoso FE, Jankovic J: Hereditary motor-sensory neuropathy and movement disorders. Muscle Nerve 1993;16(9):904-910
  6. Gemignani F, Marbini A: Charcot-Marie-Tooth disease (CMT): distinctive phenotypic and genotypic features in CMT type 2. J Neurol Sci 2001:184(1):1-9
  7. Skre H: Genetic and clinical aspects of Charcot-Marie-Tooth's disease. Clin Genet 1974;6(2):98-118
  8. Charcot JM, Marie P: Sur une forme particulière d'atrophie musculaire progressive, souvent familiale débutant par les pieds et les jambes et atteignant plus tard les mains. Rev de Med 1886;6:97-138
  9. Guyton GP, Mann RA: The pathogenesis and surgical management of foot deformity in Charcot-Marie-Tooth disease. Foot Ankle Clin 2000;5(2):317-326
  10. Parry GJ (ed): Charcot-Marie-Tooth Disorders: A Handbook for Primary Care Physicians. Upland, Pennsylvania, The Charcot-Marie-Tooth Association, 1995, pp 43-56, 103-117
  11. Pareyson D: Guidelines for the diagnosis of Charcot-Marie-Tooth disease and related neuropathies. Ad hoc Working Group of the Peripheral Nervous System Study Group, Italian Neurological Society. Ital J Neurol Sci 1999;20(4):207-216 [published erratum in Ital J Neurol Sci 1999;20(6):400]


Dr Stadler is a primary care sports medicine physician in the department of orthopedic surgery at Scott & White Memorial Hospital and Clinic at the Texas A&M University Health Science Center College of Medicine in Temple, Texas. Dr Ross is a primary care sports medicine physician at Methodist Hospitals of Dallas. Address correspondence to Teresa S. Stadler, MD, Dept of Orthopedic Surgery, Scott & White Memorial Hospital and Clinic, Texas A&M University Health Science Center College of Medicine, 2401 South 31st St, Temple, TX 76508; e-mail to [email protected].

Disclosure information: Drs Stadler and Ross disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.


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