• Clinical science

Myotonic syndromes

Abstract

Myotonic syndromes are a heterogenous group of inherited disorders with similar pathological mechanisms. Myotonic syndromes are subdivided into the rare non-dystrophic myotonic syndromes and more common myotonic dystrophies. 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

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Clinical features

Non-dystrophic myotonic syndromes

The predominant symptom in all non-dystrophic myotonic syndromes is painful tension in the muscles caused by prolonged muscle contractions. In general, it is accompanied by a loss of strength (esp. Becker muscular dystrophy); however, this may go unnoticed by the affected person.

  • Thomsen's disease
    • Muscles primarily affected: leg, eyes, tongue, and jaw
    • No atrophy, but hypertrophy (athletic physique, Hercules-like appearance)
    • Initial difficulties in muscle relaxation (e.g., delayed release from a handshake), improvement through repeated contractions (warming up)
  • Becker's disease
    • Myotonia of the legs more pronounced
    • Possibly weakness in the arms
  • Eulenburg's disease
    • Clinical features: Myotonia and flaccid paralysis occur especially in the cold. The weakness of the muscle increases with muscle activity (myotonia paradoxa).
    • Clinical manifestation: from birth

Myotonic dystrophies

Myotonic dystrophy type I

(DM1, Curschmann-Steinert disease)

Myotonic dystrophy type II

(DM2, proximal myotonic myopathy)

  • Most common in the distal sections of extremities: face, neck, forearm, foot dorsiflexor, intrinsic muscles of the hand
  • Myopathic facies
  • Clinical myotonia
  • Respiratory involvement, dysphagia, dysarthria, irritable bowel-like symptoms (e.g., abdominal pain, bloating), impaired sleep, daytime somnolence are common
  • Most common in the proximal muscles: neck flexors, hip flexors, elbow flexors, finger flexors
  • Mild clinical myotonia
  • Uncommon symptoms: respiratory muscle involvement, dysphagia, dysarthria, irritable bowel-like symptoms (e.g., abdominal pain, bloating), impaired sleep, daytime somnolence are uncommon

References:[1]

Diagnostics

Non-dystrophic myotonic syndromes

  • Percussion myotonia: myotonia can be triggered by tapping with a reflex hammer
  • EMG: repetitive discharges that wax and wane in both frequency and amplitude (crescendo-decrescendo sound), synonym: "dive bomber" sound

Myotonic dystrophies

References:[3][1]

Differential diagnoses

Non-dystrophic myotonic syndromes

Myotonic dystrophies Duchenne muscular dystrophy Becker muscular dystrophy

Myotonia congenita Thomsen

(Thomsen's disease)

Myotonia congenita Becker

(Becker's disease)

Paramyotonia congenita Eulenburg

(Eulenburg's disease)

Type 1 (DM1; Curschmann-Steinert disease) Type 2 (DM2; Proximal Myotonic Myopathy, PROMM)
Onset
  • From childhood
  • 5–35 years
  • From infancy
  • Congenital, juvenile, or adult-onset
  • Adulthood
  • 2–3 years of age
  • Usually > 15 years of age
Genetics
Defect
  • Sodium channel
  • Myotonin-protein kinase in skeletal and heart muscle, gonads, and brain
  • Complete impairment (DMD) of the dystrophin protein
  • Partial impairment (DMD) of the dystrophin protein
Clinical features
  • No atrophy, but hypertrophy
  • Initial difficulties in muscle relaxation
  • Primarily affected muscles: legs, eyes, tongue, jaw
  • No atrophy, but hypertrophy
  • Initial difficulties in muscle relaxation
  • Primarily affected muscles: legs, eyes, tongue, jaw
  • Possibly upper extremities affected
  • Muscle weakness in the cold
  • Severe disease
  • Skeletal muscle weakness and myotonia is more common in the distal muscles of all extremities: face, neck, forearm, foot dorsiflexor, intrinsic muscles of the hand
  • Myopathic facies
  • Mild disease
  • Skeletal muscle weakness and myotonia is more common in the proximal muscles: neck flexors, hip flexors, elbow flexors, finger flexors

References:[4][1]

The differential diagnoses listed here are not exhaustive.

Treatment

Non-dystrophic myotonic syndromes

  • Incurable
  • Frequently no need for treatment
  • If necessary, sodium channel blocker (e.g., carbamazepine, tocainide, mexiletine)

Myotonic dystrophies

  • Incurable
  • Symptomatic treatment; (e.g., analgesia, physiotherapy, walking aids, pacemaker, medical therapy for myotonia )
  • Regular monitoring (i.e., of respiratory compromise, dysphagia)
  • Genetic counseling and testing

References:[1][2]

Prognosis

Non-dystrophic myotonic syndromes

  • No progression of symptoms in the course of non-dystrophic myotonic syndromes
  • No effect on lifespan

Myotonic dystrophies

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