Myotonia Congenita

Key Points:

  • Myotonia congenita is caused by a mutation in a gene (CLCN1) that encodes a skeletal muscle chloride channel, which leads to delayed relaxation of skeletal muscles following voluntary action, mechanical stimulation, or emotional stimulation 
  • Patients may initially be seen for a primary complaint of frequent falls, which puts them at increased risk for traumatic injuries
  • Treatment is usually focused on symptom management, although there are some pharmacological treatment options

Description:

  Myotonia congenita affects the entire voluntary musculature, causing abnormal delay in muscle relaxation following voluntary forceful contraction or mechanical or emotional stimulation (Lossin, 2008; George, 1993). It is caused by mutations in the gene CLCN1, which encodes skeletal muscle chloride channel C1C-1. While chloride ions do not actively set the resting potential across skeletal muscle fiber cell membranes, or sarcolemma, they do respond to any change in the membrane potential. Therefore, in skeletal muscle, chloride conductance is important as an electrical buffer to stabilize the resting potential and promote repolarization after an action potential. Thus, when chloride conductance in myotonic muscle is reduced or absent, persistent muscle contraction and delayed relaxation after voluntary movement will result (Lossin, 2008).

Epidemiology:

  Myotonia congenita is inherited as an autosomal-dominant trait in Thomsen Disease or recessive trait in recessive generalized myotonia (RGM), or Becker myotonia. The best estimate for the prevalence is 1:23,000 for Thomsen Disease and 1:50,000 for RGM. 

Clinical Findings:

  Patients with Thomsen myotonia have symptoms starting at birth, while those with RGM present later in infancy or early childhood.  Neither disease is progressive over time. They may initially present being described as “clumsy” or having frequent fall (Lossin, 2008). They may report difficulty with the initiation of activity or stiffness after rest (Karol, 2014). Interestingly, the stiffness experienced usually remits with several repetitions of the same movement, which has been described as the “warm-up” phenomenon (Lossin, 2008). While the severity of symptoms in Thomsen disease can range from mild to moderate, with severe symptoms being rare, those with RGM have a more severe myotonia and can experience transient periods of muscle weakness, especially when initiating movement after rest (Lossin, 2008). The myotonia can be tested with a reflex hammer; any skeletal muscle that is struck will contract and maintain this contraction for several seconds before relaxing (Karol, 2014). Otherwise, individuals with myotonia congenita will not have any underlying muscle weakness and their neurological examination is normal. In fact, hypertrophy of muscles develops, either early in childhood or over time, leading to a “Herculean” appearance. Patients have a normal life expectancy (Lossin, 2008).

Imaging Studies:

  Imaging studies are not required in myotonia congenita unless a fall from a myotonic event raises concern for injury.

Etiology:

  Thomsen disease is most often caused by a heterozygous missense mutation, although there are exceptions. RGM can be caused by missense, nonsense, and frameshift mutations. Unique mutations occur in families or in isolated incidences. Additionally, there may be incomplete penetrance or variable expressivity that explain variable severity. (Lossin, 2008)

Treatment:

  Most patients do not require treatment and instead avoid situations or activities that trigger myotonic episodes (Lossin, 2008). Nonpharmalogical therapies such as relaxation techniques can be beneficial. Most of the pharmacological therapies that have been used act by use-dependent block of voltage-gated sodium channels. To date, there have been no controlled drug trials for myotonia congenita to evaluate the efficacy and tolerance of these drugs. 

Complications:

  Patients have a compromised ability for self-righting following loss of balance (Lossin, 2008). Furthermore, with transient weakness, patients may feel a “wave” of weakness or muscle failure affecting muscles involved in a task (Karol, 2014). This may put patients at an increased risk of falls or trauma.

Laboratory Findings:

Pathology of muscle fibers will show hypertrophy, but no dystrophic changes. EMGs will also show myotonia. However, serum CK and aldolase levels are normal. (Karol, 2014)

References:

  1. George AL, Crackower MA, et al. (1993). Molecular basis of Thomsen’s disease (autosomal dominant myotonia congenita). Nature Genetics, 3(4), 305-310.
  2. Karol LA. Muscle Diseases: Metabolic Diseases of Muscle. In: Herring, JA. (ed): Tachdjian’s Pediatric Orthopaedics: From the Texas Scottish Rite Hospital for Children (5th ed). Philadelphia: Elsevier, 2014. pp. 349-351.
  3. Lossin C & George AL. Chapter 2 Myotonia Congenita. In: Advances in Genetics. 2008; Vol 63. Pp. 25-55.

Top Contributors:

Erin Honcharuk MD
Dominick Tuason MD