• Clinical science

Myotonic syndromes

Summary

Myotonic syndromes are a heterogenous group of inherited disorders with similar pathological mechanisms. 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

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: Classically manifests as difficulty releasing a handshake.
  • 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

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.

References:[1]

Diagnostics

References:[3][1]

Differential diagnoses

Myotonic dystrophies Duchenne muscular dystrophy Becker muscular dystrophy
Type 1 (DM1; Curschmann-Steinert disease) Type 2 (DM2; Proximal Myotonic Myopathy, PROMM)
Onset
  • Congenital, juvenile, or adult-onset
  • Adulthood
  • 2–3 years of age
  • Usually > 15 years of age
Genetics
Defect
  • 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
  • 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

  • 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

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