What are the symptoms and recommended treatments for Myotonia Congenita?

Myotonia Congenita: Symptoms and Treatment

Myotonia congenita is a genetic muscle disorder caused by CLCN1 gene mutations that presents with muscle stiffness (delayed relaxation after contraction) and muscle hypertrophy, treated primarily with mexiletine to reduce myotonic symptoms and improve quality of life.

Clinical Symptoms

Primary Manifestations

• Muscle stiffness and delayed relaxation after voluntary contraction, particularly when rising from chairs, starting to climb stairs, or after forceful grip 1, 2
• Warm-up phenomenon: symptoms improve with repeated muscle activity and exercise 1, 2
• Generalized muscle hypertrophy, with pronounced hypertrophy of calf muscles creating an "athletic" appearance 1, 3
• Proximal muscle weakness may be present, particularly in the recessive (Becker) form 1, 3

Age of Onset and Inheritance Patterns

• Becker type (autosomal recessive): onset typically between 2-15 years of age, more severe phenotype with proximal weakness 4
• Thomsen type (autosomal dominant): onset between 4-20 years of age, generally milder presentation 4
• Both forms affect males and females equally 4

Functional Impact

• Muscle stiffness worsens after periods of rest 1
• Can lead to school or work absenteeism due to functional limitations 1
• No cardiac involvement (distinguishing it from myotonic dystrophy) 1

Diagnostic Confirmation

Electromyography

• Myotonic discharges producing characteristic "dive-bomber sound" on needle insertion 1, 2
• Myopathic changes with polyphasic motor unit action potentials of short duration and low amplitude 5

Genetic Testing

• Mutations in CLCN1 gene encoding the voltage-gated chloride channel ClC-1 1, 4, 6
• Over 200 CLCN1 mutations identified, predominantly missense mutations 4, 6
• In Chinese populations, exon 8 variants are most prevalent, with c.892G>A (p.A298T) being a potential founder mutation 2
• Next-generation sequencing or targeted gene panel testing confirms diagnosis 1, 2

Treatment Approach

First-Line Pharmacotherapy

Mexiletine is the primary treatment for symptomatic myotonia congenita, providing significant relief of muscle stiffness 1, 3

• Mexiletine acts as a sodium channel blocker to reduce myotonic discharges
• Patients show significant improvement in muscle stiffness and functional capacity 1, 3
• Regular monitoring is required during treatment 1

Treatment Outcomes

• Pharmacotherapy with proper monitoring can remarkably improve quality of life 1
• Patients on regular mexiletine therapy demonstrate sustained improvement on follow-up 1, 3
• Treatment is relatively simple compared to other neuromuscular disorders and provides significant symptomatic relief 1

Important Clinical Considerations

Distinguishing from Myotonic Dystrophy

• Myotonia congenita does NOT involve cardiac complications, unlike myotonic dystrophy types 1 and 2 which have 80% cardiac involvement 7, 5
• No progressive multisystem involvement (cataracts, intellectual impairment, endocrine abnormalities) seen in myotonic dystrophy 7
• Muscle hypertrophy is prominent in myotonia congenita, whereas myotonic dystrophy causes progressive muscle wasting 7

Genetic Counseling

• Parents with consanguinity have higher risk of autosomal recessive (Becker) form 3
• Antenatal diagnosis should be offered for future pregnancies in affected families 3
• Intrafamilial phenotypic variability can occur, with incomplete penetrance in some Thomsen families 4

Pitfalls to Avoid

• Do not overlook myotonia congenita in children presenting with "athletic build" and exercise-related complaints 1
• Always test for myotonia clinically (delayed hand relaxation after forceful grip) in children with proximal weakness 1
• Do not assume cardiac screening is necessary as in myotonic dystrophy—cardiac involvement does not occur in myotonia congenita 1