Myotonia Congenita

Written by: Dr Jeremy Steinberg – created: 8 March 2023; last modified: 12 March 2023

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Myotonia Congenita
Inheritance	Autosomal dominant (Thomsen) or recessive (Becker)
Genetics	CLC1N pathogenic variant

Myotonia Congenita is a genetic disease characterised by skeletal muscle stiffness from childhood. It sits in a group of disorders known as nondystrophic myotonias to differentiate them from the myotonic dystrophies as the tissues are not dystrophic. It is also known as chloride channel myotonia because it is a chloride channelopathy. The nondystrophic myotonias can be painful and so the Musculoskeletal Physician should be aware of them.

Genetics

There is a loss of function mutation in the CLCN1 gene. Myotonia Congenita can be autosomal dominant which is called Thomsen disease or autosomal recessive which is called Becker disease. The same pathogenic variant can be associated with both forms.

Epidemiology

The prevalence is 1 in 100,000.

Clinical Features

Patients have episodes of muscle stiffness (myotonia) or cramping that typically begins in childhood. However the age of onset is highly variable. AR myotonia congenita typically occurs later than the AD form, but in both forms the age of onset can be as late as ones 20s to 30s.

The AR form typically has more severe manifestations including progressive, minor distal weakness, and transient weakness with movement following a period of rest. The stiffness is often alleviated by brief exercise which is called the "warm-up" effect.

Pain is common but usually not as severe as in myotonic dystrophy type 2.

Unlike with Myotonic Dystrophy, systemic manifestations do not generally occur. However a minority may have cardiac conduction defects.

On examination there may be percussion myotonia. All skeletal muscle groups can be affected including the eyes, face, and tongue. The muscles may appear hypertrophic.

Clinical Features of AR vs AD Myotonia Congenita

Feature	AR Myotonia Congenita	AD Myotonia Congenita
Age of onset	Early childhood	Early infancy
Muscle stiffness	Generalized, legs>arms	Generalized, arms>legs
Muscle hypertrophy	Generalized	Generalized
Pain	Very common	Common
Transient muscle weakness	Common	Not present
Distal muscle weakness	Rarely	Not present
Proximal muscle weakness	Rarely	Not present

Investigations

CK is typically elevated <3-4 times the upper limit of normal. EMG may show myotonic bursts.

Diagnosis

The diagnosis is made through molecular genetics by finding a heterozygous pathogenic variant or biallelic pathogenic variants of the CLCN1 gene. There are no clinical diagnostic criteria.

Differential Diagnosis

The following are all the myotonic disorders. The presence of muscle wasting and systemic manifestations suggests myotonic dystrophy.

Myotonia Differential Diagnosis

• Myotonic dystrophy
  • DM type 1 (DMPK)
  • DM type 2 (CNBP)
• Non-dystrophic myotonias
  • Chloride channelopathies (CLCN1)
    • Thomsen myotonia congenita
    • Becker myotonia congenita
  • Sodium channelopathies (SCN4A)
    • Sodium channel myotonia
    • Paramyotonia congenita
    • Hyperkalaemic periodic paralysis
  • Chondrodystrophic myotonia
• Drug induced (statins, fibrates, cyclosporine, chloroquine, terbutaline, formoterol, propranolol)
• Isolated electrical myotonia: Pompe Disease, Polymyositis, Myotubular congenital myopathy, hypothyroidism, malignant hyperpyrexia, severe denervation.

Treatment

Mexiletine has the best documented effect, which is a sodium channel blocker.

Resources

GeneReviews - Myotonia Congenita

Nondystrophic myotonias guidelines - Stunnerberg 2020 - 2.05 MB (f)

Literature Review

Literature Review

Reviews from the last 7 years: review articles, free review articles, systematic reviews, meta-analyses, NCBI Bookshelf

Articles from all years: PubMed search, Google Scholar search.

TRIP Database: clinical publications about evidence-based medicine.

Other Wikis: Radiopaedia, Wikipedia Search, Wikipedia I Feel Lucky, Orthobullets,