Myotonia Congenita

Daube JR, Cascino GD, Dotson RM, Silber MH, Westmoreland BF. Electromyography and nerve conduction studies. Continuum Lifelong Learning Neurol 1998;4(5):101-102.

and

Saperstein DS. Muscle channelopathies. Continuum Lifelong Learning Neurol 2006;12(3): 121-125.

1. General Information

Myotonia congenita is a channelopathy due to a point mutation in the muscle chloride channel gene CLCN1 on chromosome 7. Over 50 mutations have been described.  Abnormal chloride ion conductance in the muscle membrane is thought to be responsible for the spontaneous prolonged and repetitive firing of muscle fibers, which may be seen at rest or after voluntary activity.  The spontaneous activity manifests as myotonic discharges, muscle fiber action potentials that wax and wane in amplitude and frequency due to the muscle membrane abnormality.  The variable discharge frequency of 40 to 100 per second accounts for the characteristic sound during EMG needle testing, likened to a bomber aircraft diving toward its target.

2. Symptoms and Signs

Myotonia is the consequence of impaired muscle relaxation and may cause nonspecific cramping or muscle pain, particularly after activation.  Muscles may tighten or “lock-up” on attempting sudden activity and falls may occur on first trying to walk or sprint.  Eye closure myotonia may be seen as delayed eyelid opening after forceful eye closure, for example in infants after a crying spell.  In severe cases myotonia may impair chewing and swallowing.  Difficulty releasing a grip (grip myotonia) is commonly experienced such as after turning a doorknob, grasping a handle or after a handshake.  A warm-up phenomenon is seen with improvement in myotonia upon continued repetitive activity.  Reduction in myotonia after several repetitions is consistent with the warm-up phenomenon.  Percussion myotonia is commonly tested by tapping the thenar eminence with a reflex hammer.  This generally results in thumb elevation/abduction and slow relaxation over a few seconds.  Percussion of the extensor digitorum communis muscle while the forearm is extended and the wrist is hanging down may elicit sustained reflex extension of the wrist and fingers for a second or more.  The severity of myotonia may fluctuate within an individual and vary among affected family members.

There are two forms of myotonia congenita, an autosomal dominant (Thomsen disease) and an autosomal recessive (Becker disease which should not to be confused with the dystrophinopathy).  Age of onset is earlier in the dominant form, usually within the first 2 years of life, as compared to between 4 to 12 years in the recessive form.  The recessive form tends to be associated with more severe symptoms and gradually progresses in the first two decades of life. Limb stiffness tends to be worse in the legs and to a greater degree proximal than distal.  After a severe bout of myotonia, transient muscle weakness may occur, especially in the hands.  Some individuals develop mild fixed weakness with a distal predominance.  Muscle weakness is unusual in Thomsen disease as opposed to myotonic dystrophy.

3. Diagnosis

The diagnosis of myotonia congenita is based on the clinical history, the findings of myotonia without prominent weakness, and supportive electrodiagnostic evidence of myotonic discharges both at rest and with volitional activity.  Serum CK levels are usually normal or slightly elevated.  Electrical myotonia is not unique to myotonia congenita and can be seen in other conditions including myotonic dystrophy, paramyotonia, hyperkalemic periodic paralysis, polymyositis, acid maltase deficiency and toxic myopathies.  Serum creatine kinase levels may be mildly elevated but are usually normal.  Chloride channel gene testing is commercially available to confirm the diagnosis and to help guide genetic counseling.

4. Treatment

Most patients with myotonia congenita do not require symptomatic treatment with medication.  When myotonia is severe, antiarrhythmic or antiepileptic medications that interfere with sodium channel function may be beneficial, but these have not been well-studied in prospective trials.  Mexiletine is often used as it reduces myotonia and may prevent the transient weakness that can occur in Becker form of the disease.  An electrocardiogram should be obtained prior to use of mexiletine and periodically after to ensure there are no cardiac conduction abnormalities.  A cardiologist should be consulted if the latter are found.  Dantrolene may also be helpful in reducing muscle stiffness by acting to block the release of calcium from the sarcoplasmic reticulum.

5. Remember

Neurophysiology in MC:

Routine NCS are normal.  Needle EMG shows myotonic discharges at rest and during volitional activity. It may be difficult to appreciate MUAPs as myotonic discharges may obscure the voluntary MUAPs, but morphology and recruitment is usually normal.  Short duration, small amplitude MUAPs may be occasionally seen in weak muscles.  SFEMG reveals normal fiber density but slightly increased jitter.  On RNS, a decrement is appreciated when a prolonged train of stimuli are delivered at 10 Hz or more.  The CMAP amplitude may decrease to 65% of normal and even to more percentage of decrement if stimulation is given at higher rates.  The SET is associated with a decrease in CMAP amplitude immediately after exercise and return to baseline after 20-40 seconds, in 48-80% of individuals with MC.  The reduction in CMAP amplitudes is lesser with repeated trials of SET corresponding to the clinical warm-up phenomena.  This is called Fournier pattern II.  A greater than 40% decrement of SET is specific for MC.  It is seen in AR forms (Becker's) MC, while the AD (Thomsen) MC is not associated with significant change.  However, performing the SET in a cooled limb in these patients (AD form) may result in drop of CMAP amplitude that later improves with repeated SET (normal converted to type II with cold).  In AR form of MC, there is no difference in results when SET is performed in a warm or cool limb (remains type II).  PEMPs (post-exercise repetitive discharges) are seen in 1/3 of MC after short exercise but disappear within 10-30 seconds after exercise.  LET is usually normal.