Myotonia Congenita
Myotonia Congenita is a genetic disease characterised by skeletal muscle stiffness from childhood. It is also known as chloride channel myotonia.
Genetics
The relevant gene is CLCN1. 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.
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.
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
- Myotonic dystrophy type 1 and 2
- Myotonia congenita
- Cold induced myotonia (paramyotonia)
- Hyperkalaemic periodic paralysis
- Chondrodystrophic myotonia
- Drug induced (statins, fibrates, cyclosporine, chloroquine)
Treatment
Mexiletine has the best documented effect, which is a sodium channel blocker.
Resources
GeneReviews - Myotonia Congenita
References
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,