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Myotonic syndromes

Last updated: October 12, 2021

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Myotonic syndromes are a heterogeneous group of inherited disorders with similar pathological mechanisms. Myotonic syndromes are subdivided into dystrophic myotonic syndromes and nondystrophic myotonic syndromes. Nondystrophic myotonic syndromes are channelopathies and include Thomsen disease, Becker disease, and Eulenberg disease. The channelopathies are autosomal dominant or autosomal recessive conditions caused by defective ion channels in the skeletal muscle sarcolemma. All three diseases manifest with myotonia, muscle stiffness, and weakness. Thomsen disease and Becker disease are furthermore characterized by muscular hypertrophy. Myotonic dystrophies, the most prevalent myotonic syndromes, are one of the most common forms of adult-onset muscular dystrophy. Both types, myotonic dystrophy type I (Curschmann-Steinert disease) and myotonic dystrophy type II (proximal myotonic myopathy), are autosomal dominant conditions with CTG trinucleotide repeat and CCTG tetranucleotide repeat expansions respectively. Type I is a severe (often life-threatening) form of disease, while type II is usually mild. Both present with skeletal muscle weakness and myotonia, muscle pain, heart conduction defects, cataracts, testicular atrophy, and frontal balding. Electromyography may confirm myotonia that is not identified during clinical examination; however, genetic tests usually confirm the diagnosis. As no curative therapy exists, treatment is symptomatic. Except for DM1, patients with myotonic syndromes have a normal lifespan.

Epidemiology [1][2]

Etiology

Clinical features [1]

Clinical features of myotonic dystrophies

Myotonic dystrophy type I (DM1, Curschmann-Steinert disease)

Myotonic dystrophy type II (DM2, proximal myotonic myopathy)

Clinical features
Typical location
  • The proximal muscles: neck flexors, hip flexors, elbow flexors, finger flexors
Symptom onset
  • Congenital, juvenile, or adult onset
  • Usually adult onset

Myotonic dystrophy type I is caused by a CTG nucleotide repeat expansion and results in Cataracts, Toupee (premature hair loss in men), and Gonadal atrophy.

Diagnostics [1][3]

Treatment [1][2]

Prognosis

  • The course of DM1 is chronic progressive. Cardiac complications reduce life expectancy.
  • DM2 has a milder disease course.

Epidemiology [4]

Etiology and clinical features [5] [4]

Myotonia congenita (Thomsen disease) Myotonia congenita (Becker disease) Paramyotonia congenita (Eulenburg disease)
Inheritance
Pathophysiology
Symptom onset
  • Childhood (first decade of life)
  • 5–35 years
  • Congenital
Typical location
  • Lower extremities more than upper extremities
  • Face, eyes, tongue, and hands are most commonly affected
Clinical features
  • Myotonia (e.g., delayed release from a handshake)
  • Transient muscle weakness
  • Muscle stiffness
  • Warming-up effect: Symptoms improve through repeated contractions.
  • Muscular hypertrophy (athletic physique)
  • Painful myotonia and episodic muscle weakness
  • Precipitating factors
    • Cold temperatures
    • Strenuous exercise (paradoxical myotonia)

Diagnostics

  • Percussion myotonia: percussion of a muscle results in myotonia with delayed muscle relaxation (e.g., tapping the thenar eminence with a reflex hammer causes the thumb to abduct)
  • EMG: repetitive discharges with oscillating frequency and amplitude (crescendo-decrescendo sound )
  • Genetic testing: confirms the diagnosis

Treatment [5]

Prognosis

  • Incurable
  • Varying degree of life-long disability but no effect on life expectancy
  • No symptom progression throughout the course of the disease

Overview of myotonic syndromes

Comparison of myotonic syndromes and muscular dystrophies [1]
Types Onset Pathophysiology Clinical features
Myotonic dystrophies Type 1 (DM1)
  • Congenital, juvenile, or adult-onset
Type 2 (DM2)
  • Adulthood
Nondystrophic myotonic syndromes

Thomsen disease

  • From childhood

Becker disease

  • 5–35 years

Eulenburg disease

  • Paradoxical myotonia (worsens with exercise)
  • Muscle weakness exacerbated by cold temperatures
Duchenne muscular dystrophy
  • 2–5 years of age
Becker muscular dystrophy
  • Usually > 15 years of age

Periodic paralysis (PP)

Overview of periodic paralysis [6][7]
Types Hypokalemic PP Hyperkalemic PP Thyrotoxic PP Andersen-Tawil syndrome
Definition
  • A group of rare muscular conditions characterized by recurrent episodes of muscle weakness that typically develop after strenuous exercise, changes in diet, or medication use
Epidemiology [8]
  • Most common type
  • >
  • 1:100,000
  • Peak age of onset: late childhood and adolescence
  • =
  • 1:200,000
  • Peak age of onset: early childhood
  • =
  • Peak age of onset: > 20 years of age
  • 1:1,000,000
  • Peak age of onset: childhood and adolescence
Etiology
Triggers
  • Potassium-rich meals
  • Rest after exercise
  • Exposure to cold temperatures
  • Fasting
  • Pregnancy
  • Anesthesia
  • Stress
  • Exercise
  • Prolonged periods of rest
Clinical features Common
  • Attacks of focal or generalized flaccid muscle weakness (periodic paralysis)
    • Proximal muscles are more prominently affected; respiratory and facial muscles are generally spared
    • Variable duration (hours to days)
    • Concomitant fatigue, muscle pain, and/or altered state of consciousness during the attacks
  • Neurological examination is usually normal between attacks.
Specific
  • Infrequent attacks of muscle weakness (e.g., transient paraparesis or quadriparesis)
  • Hyporeflexia or areflexia
  • Variable myopathy can develop over time
Diagnostics Laboratory analysis
  • ↓ K+
  • ↔︎/↑ K+
  • ↔︎/↑/↓ K+
EMG
  • Positive sharp waves
  • Repetitive discharges that wax and wane in both frequency and amplitude [9]
Long exercise test
  • Procedure: stimulation of a nerve (e.g., ulnar nerve) and recording of compound muscle action potentials (e.g., of the adductor digiti minimi muscle)
  • Positive test: ≥ 40% reduction in muscle action potential amplitude or > 50% area reduction during or post exercise
  • During an attack, the test is positive in all types of PP.
Muscle biopsy
  • May show normal findings or signs of myopathy (e.g., muscle fiber atrophy, variable muscle fiber sizes, split fibers) [10]
Differential diagnoses
Acute treatment Mild attacks
  • May subside spontaneously or resolve with low-intensity exercise (e.g., walking around a room)
Severe attacks
  • Oral potassium chloride until serum potassium levels normalize
  • N/A
Prevention
  • N/A

The differential diagnoses listed here are not exhaustive.

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  2. Statland JM, Fontaine B, Hanna MG, et al. Review of the Diagnosis and Treatment of Periodic Paralysis. Muscle Nerve. 2017; 57 (4): p.522-530. doi: 10.1002/mus.26009 . | Open in Read by QxMD
  3. Veerapandiyan A, Statland JM, Tawil R, et al. Andersen-Tawil Syndrome. GeneReviews. 1993 .
  4. Fontaine B. Periodic paralysis.. Adv Genet. 2008; 63 : p.3-23. doi: 10.1016/S0065-2660(08)01001-8 . | Open in Read by QxMD
  5. Mills KR. The basics of electromyography. Journal of Neurology, Neurosurgery & Psychiatry. 2005; 76 (suppl_2): p.ii32-ii35. doi: 10.1136/jnnp.2005.069211 . | Open in Read by QxMD
  6. Burakgazi AZ. Delayed diagnosed atypical case of Andersen-Tawil syndrome. Neurology International. 2019; 11 (2). doi: 10.4081/ni.2019.8180 . | Open in Read by QxMD
  7. Matthews E, Fialho D, Tan SV, et al. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain. 2009; 133 (1): p.9-22. doi: 10.1093/brain/awp294 . | Open in Read by QxMD
  8. Myotonic syndromes. https://www.ncbi.nlm.nih.gov/pubmed/12351998. Updated: October 1, 2002. Accessed: April 2, 2017.
  9. Trivedi JR, et al.. Nondystrophic Myotonia: Challenges and Future Directions. Experimental Neurology. 2013 .
  10. Matthews E., et al.. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain. 2009 .