Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Myotonic syndromes

Last updated: July 14, 2021

Summary

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.

Dystrophic myotonic syndromes

Epidemiology ^[1]^[2]

One of the most common forms of adult-onset muscular dystrophy

Etiology

Autosomal dominant conditions
Type 1: CTG trinucleotide repeat expansion in the DMPK gene → changes in myotonin protein kinase expression
Type 2: CCTG tetranucleotide repeat expansion of the ZNF9 gene (CNBP gene)

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	Myotonia: delayed muscle relaxation following normal muscle contraction Skeletal muscle weakness(due to muscle atrophy) Myalgia Arrhythmia Cataracts Testicular atrophy or features of ovarian insufficiency (i.e., infertility) Frontal balding Hypogammaglobulinemia Features of insulin resistance Cognitive impairment
Clinical features	Myopathic facies Long, narrow face Hollowed cheeks, and high arched palate Ptosis Sternocleidomastoid muscle atrophy 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	Mild clinical myotonia Uncommon symptoms: respiratory muscle involvement, dysphagia, dysarthria, irritable bowel-like symptoms (e.g., abdominal pain, bloating), impaired sleep, daytime somnolence
Typical location	The distal sections of extremities: face, neck, forearm, foot dorsiflexor, intrinsic muscles of the hand.	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]

Electromyography (EMG): allows for the identification of myotonia
Genetic diagnostics: (confirmatory test) detection of trinucleotide repeat expansion mutation in leukocytes
Biopsy: to distinguish between an inflammatory and a metabolic cause of the myopathy
Other supportive tests
- ↑ CK, IgG and IgM hypogammaglobulinemia, ↑ FSH, and ↓/normal testosterone
- ECG: to exclude cardiac arrhythmias and other abnormalities
- MRI: signs of global atrophy

Treatment ^[1]^[2]

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

Prognosis

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

Nondystrophic myotonic syndromes

Epidemiology ^[4]

Rare disorders (prevalence < 1:100,000)

Etiology and clinical features ^[5] ^[4]

	Myotonia congenita (Thomsen disease)	Myotonia congenita (Becker disease)	Paramyotonia congenita (Eulenburg disease)
Inheritance	Autosomal dominant	Autosomal recessive	Autosomal dominant
Pathophysiology	Loss of function mutation in the CLCN gene → defective chloride channel in skeletal muscle		SCN4A gene mutation → defective sodium channel in skeletal muscle sarcolemma
Symptom onset	Childhood (first decade of life)	5–35 years	Congenital
Typical location	Legs, eyes, tongue, and jaw	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)	Same as Thomsen disease but symptoms are more severe	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]

Mild cases
- Usually no treatment necessary
- Avoid precipitating factors, e.g., strenuous exercise.
Severe cases
- Sodium channel blocker (e.g., mexiletine, carbamazepine, tocainide)
- Acetazolamide

Prognosis

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

Differential diagnoses

Differential diagnoses of myotonic syndromes ^[1]
		Onset	Pathophysiology	Clinical features
Myotonic dystrophies	Type 1 (DM1)	Congenital, juvenile, or adult-onset	Autosomal dominant CTG trinucleotide repeat in the region of: DM1: DMPK gene (a gene that encodes dystrophia myotonica protein kinase) DM2: ZNF9 gene (CNBP gene) Myotonin-protein kinase in skeletal and heart muscle, gonads, and the brain	Myalgia Arrhythmias Cataracts Testicular atrophy or features of ovarian insufficiency (i.e., infertility) Frontal balding	Severe disease Skeletal muscle weakness and myotonia More common in the distal muscles of the extremities: face, neck, forearm, foot dorsiflexor, intrinsic muscles of the hand Myopathic facies
Myotonic dystrophies	Type 2 (DM2)	Adulthood			Mild disease Skeletal muscle weakness and myotonia is more common in proximal muscles: neck flexors, hip flexors, elbow flexors, finger flexors
Nondystrophic myotonic syndromes	Thomsen disease	From childhood	Autosomal dominant Defective chloride channel	No atrophy, but hypertrophy Initial difficulties in muscle relaxation Primarily affected muscles: Legs, eyes, tongue, jaw In Becker disease: possibly upper extremities
	Becker disease	5–35 years	Autosomal recessive Defective chloride channel
	Eulenburg disease	From infancy	Autosomal dominant Defective sodium channel	Paradoxical myotonia (worsens with exercise) Muscle weakness exacerbated by cold temperatures
Duchenne muscular dystrophy		2–5 years of age	X-linked recessive Chromosomal defect affects the dystrophin gene on the short arm of the X chromosome (Xp21) → frameshift mutation Complete impairment (DMD) of the dystrophin protein	Paresis and atrophy starting in the proximal lower limbs, later spreading to the upper body and distal areas Weak reflexes Bilateral Trendelenburg sign Gower maneuver Calf pseudohypertrophy
Becker muscular dystrophy		Usually > 15 years of age	X-linked recessive Chromosomal defect affects the dystrophin gene on the short arm of the X chromosome (Xp21) → in-frame mutation Partial impairment (DMD) of the dystrophin protein	Symptoms identical to those of Duchenne muscular dystrophy, but less severe Slower progression Heart involvement is more common compared to DMD.

The differential diagnoses listed here are not exhaustive.

References

Thornton CA. Myotonic dystrophy. Neurol Clin. 2014; 32 (3): p.705-719. doi: 10.1016/j.ncl.2014.04.011 . | Open in Read by QxMD
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
Myotonic syndromes. https://www.ncbi.nlm.nih.gov/pubmed/12351998. Updated: October 1, 2002. Accessed: April 2, 2017.
Trivedi JR, et al.. Nondystrophic Myotonia: Challenges and Future Directions. Experimental Neurology. 2013 .
Matthews E., et al.. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain. 2009 .

Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Myotonic syndromes

Summary

Dystrophic myotonic syndromes

Epidemiology [1][2]

Etiology

Clinical features [1]

Diagnostics [1][3]

Treatment [1][2]

Prognosis

Nondystrophic myotonic syndromes

Epidemiology [4]

Etiology and clinical features [5] [4]

Diagnostics

Treatment [5]

Prognosis

Differential diagnoses

References

Epidemiology ^[1]^[2]

Clinical features ^[1]

Diagnostics ^[1]^[3]

Treatment ^[1]^[2]

Epidemiology ^[4]

Etiology and clinical features ^[5] ^[4]

Treatment ^[5]