Myotonia congenita is a rare genetic disorder characterized by a delay in muscle relaxation after a voluntary contraction resulting in muscle stiffness, in addition to muscle hypertrophy. It manifests during childhood and is often inherited, although the exact age at which this occurs and the associated symptoms can depend on which type of myotonia congenita you have.
Myotonia describes the inability to relax muscles quickly after they have been voluntarily contracted. In some cases, myotonia can be painful and feel like muscles are tight, locked, stiff, or cramping. Myotonia can be experienced in all skeletal muscles but most commonly in the legs.1 Congenita describes that this is a trait that exists from birth - in this instance because myotonia congenita is a genetic condition.
Myotonia congenita is the most common non-dystrophic myotonia because in this condition the muscle tissue structure is not part of the pathology.2 Individuals with myotonia congenita do not have reduced life expectancy and the condition does not progress, although it may disrupt basic walking, chewing, swallowing, and grasping functions.3 It is recommended that individuals with the condition should have genetic counselling, especially to increase awareness to make more informed decisions during family planning.4
Skeletal muscles are the muscles in the body that you can voluntarily control such as facial muscles, leg muscles, and arm muscles. This is in contrast to muscles that are not voluntarily controlled such as the heart muscle and muscles that help move food through our gut. Myotonia congenita affects the skeletal muscles.
Skeletal muscles in the body are able to contract and relax because of charges moving in and out of the muscle - like electricity. To allow some of these charges to move between the inside of the muscle and the outside of the muscle, there is a gateway called the voltage-gated chloride channel (CIC-1). CIC-1 is very important for letting the chemical changes in the muscle allow the muscle to relax. In myotonia congenita, the CIC-1 does not function as it does in a healthy individual - the dysfunctional CIC-1 results in inappropriate hyperexcitability of the muscle, resulting in myotonia. The CIC-1 is dysfunctional because the gene that is responsible for making CIC-1 is faulty, so CIC-1 is not in its normal shape to let the charge pass.
The dysfunctional CIC-1 makes the charges on the outside and inside of the muscle unusual, resulting in the muscle being more excitable and more likely to contract.
Forms of myotonia congenita
Historically, there have been two main types of myotonia congenita: Becker myotonia and Thomsen myotonia. However, other forms have emerged, such as Issac myotonia, paramyotonia congenita, and pseudomyotonia.5 These more recent forms have been classed with the advent of more accessible genetic testing and identification of different forms of the faulty gene that codes for CIC-1– there are over 200 pathogenic mutations of this gene.6,7 Also, because of this, the distinction between all these forms is becoming more blurred with overlap seen between some of these and their clinical manifestations. This article will focus on Becker myotonia and Thomsen myotonia in more depth.
Becker myotonia is an autosomal recessive condition. The disease manifests between 4 to 12 years of age with symptoms in the lower limbs, at first.8 Becker myotonia displays severe myotonia. A transient weakness may also develop and it is possible that this weakness may become progressive. Additionally, Becker myotonia is associated with muscle hypertrophy which is particularly evident in the lower limbs.9
Thomsen myotonia is an autosomal dominant condition and is rarer than Becker myotonia. The disease manifests between ages 2 to 3 years old with symptoms usually in the upper limbs and face at first.10 The eyelids, hands, and legs are the places most affected by myotonia.11 Abnormal muscle enlargement can be observed from infancy.12 The symptoms of Thomsen myotonia are generally milder than those associated with Becker myotonia and there is no weakness associated with this form of myotonia congenita.13 However, identical inherited mutations of the gene in different individuals can result in various extents of symptoms in the individuals.14
- Delayed relaxation after muscle contraction, resulting in muscle stiffness (most commonly legs, less commonly face)
- Hypertrophy of skeletal muscles (“athletic” / ”herculean” / ”body-builder” appearance)
- Skeletal muscle strengthening
- Temporary attacks of muscle weakness (especially in the arms and hands)
- Mild but permanent muscle weakness
In early childhood, symptoms also include:21
- Feeding difficulties
- Reflux after feeding
- Difficulty opening eyes after crying
A clinical examination to assess myotonia may involve asking an individual to open and close their eyes or their fists and observing how the muscles respond, observing whether a warm-up phenomenon can be observed.25
Diagnosis can be done through electromyography and genetic testing, and sometimes muscle biopsy.26 Muscle biopsy is not necessary to diagnose myotonia congenita due to the widespread availability of genetic testing. Electromyography is the most useful diagnostic tool although it does have the disadvantages of being uncomfortable and time-consuming.27 Ultimately, genetic analysis should be used to reveal the mutation associated with the myotonia congenita and from there the type of myotonia congenita can be decided.
Generally, individuals with myotonia congenita do not need specific medicinal treatment and the treatment that is provided is primarily supportive such as physical therapy and rehabilitation which aim to improve muscle function.28,29 Lifestyle changes may also help to reduce the symptoms of myotonia. Exercise is said to help reduce the symptoms of myotonia whilst avoiding the cold and stress may also provide some relief.30
When symptoms are more severe, membrane-stabilising drugs may be recommended by the doctor. These medications include quinine, 1b antiarrhythmic drugs or anticonvulsant drugs.31,32 Anti-myotonic drugs show a high success rate in patients (76.2%).33 Side effects include tremor, dizziness, ataxia, and gastrointestinal disturbances but these are usually reversible and dose-dependent.34
Myotonia Congenita is a genetic condition which is inherited. Therefore, an individual who has parents who possess the pathogenic gene variant, whether or not they show symptoms of myotonia congenita, will have an increased risk of getting the disorder. It is important for adults with the genetic variant to undergo genetic counselling, especially during decisions on family planning, for this reason. To inherit the Thomsen myotonia autosomal dominant form, a child must inherit just one pathogenic gene variant from one parent. To inherit the Becker myotonia autosomal recessive form, a child must inherit two pathogenic gene variants, one from the mother and one from the father.
How common is myotonia congenita?
1 in 100,000 people have myotonia congenita.35
Are there associated complications?
Some medications are associated with adverse events in individuals with myotonia congenita. These adverse events include but are not limited to profound muscle spasms, myopathy, and difficulties in ventilation.36 Additionally, extra care must be taken for patients who are also pregnant because pregnancy worsens the symptoms of myotonia congenita.37
Medications that should be used with great caution:38
- Beta antagonists
What makes myotonia worse?
- After exercise
- Cold weather
- At the start of an activity
- After sitting still for a long time
- Menstruation (supposed association between CIC-1 and sex hormone changes)
- Being male assigned at birth
Does this condition progress?
Myotonia congenita does not progress (making it different to myotonic dystrophy). It is possible for individuals with the condition to do well in sports requiring strength rather than agility.41
What is the warm-up phenomenon?
The warm-up phenomenon of myotonia congenita describes the situation in which the symptoms of myotonia decrease when the muscles are being used continuously or rhythmically.42 This explains why starting a movement may be more difficult for people with myotonia congenita and how exercise can lessen the effects of myotonia.
Myotonia congenita is a rare inherited genetic disorder caused by a pathogenic genetic variant of the gene that encodes for a muscle channel called CIC-1 which makes the skeletal muscle more excitable and more likely to contract. Myotonia congenita is characterised by muscle stiffness, due to the inability of skeletal muscles to relax after they contract, and muscle hypertrophy. The onset of symptoms and their severity depends on the type of myotonia congenita, and ultimately the exact pathogenic gene variant present. Fortunately, this condition is not life-limiting and many individuals lead a happy and fulfilling life. Additionally, for most people, only supportive treatments, physical therapy and rehab, are required as their symptoms are manageable. Further lifestyle changes can help to relieve symptoms too. However, for those whose symptoms are more severe, anti-myotonic drugs can help and have been successful in large proportions of patients.
- Bryan ES, Alsaleem M. Myotonia congenita. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Jul 31]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK562335/.
- NHS Channelopathy Service [Internet]. Myotonia Congenita. Available from: https://channelopathy.nhs.uk/patients/types-channelopathy/myotonia-congenita/
- National Institute of Neurological Disorders and Stroke [Internet]. [cited 2023 Jul 31]. Myotonia congenita. Available from: https://www.ninds.nih.gov/health-information/disorders/myotonia-congenita
- Myotonic/myotonias | north bristol nhs trust [Internet]. [cited 2023 Jul 31]. Available from: https://www.nbt.nhs.uk/south-west-neuromuscular-operational-delivery-network/about-swnmodn/swnmodn-conditions-covered-3
- Li L, McCall C, Hu X. Editorial: innate immunity programming and memory in resolving and non-resolving inflammation. Front Immunol. 2020;11:177.
- MSD Manual Professional Edition [Internet]. [cited 2023 Jul 31]. Myotonia congenita - pediatrics. Available from: https://www.msdmanuals.com/en-gb/professional/pediatrics/inherited-muscular-disorders/myotonia-congenita
- Myotonia congenita - symptoms, causes, treatment | nord [Internet]. [cited 2023 Jul 31]. Available from: https://rarediseases.org/rare-diseases/myotonia-congenita/
- Muscular Dystrophy Association [Internet]. 2022 [cited 2023 Jul 31]. Signs and symptoms of myotonia congenita (Thomsen disease and becker type) - diseases. Available from: https://www.mda.org/disease/myotonia-congenita/signs-and-symptoms
- Li Y, Li M, Wang Z, Yang F, Wang H, Bai X, et al. Clinical and molecular characteristics of myotonia congenita in China: Case series and a literature review. Channels (Austin). 2022 Dec;16(1):35–46.
- Kuhn E. [Myotonia congenital (Thomsen) and recessive generalized myotonia (Becker)]. Nervenarzt. 1993 Dec;64(12):766–9.
- Dunø M, Vissing J. Myotonia congenita. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Jul 31]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1355/
- Muscular Dystrophy Association [Internet]. 2017 [cited 2023 Jul 31]. Myotonia congenita (Thomsen disease and becker type) - diseases. Available from: https://www.mda.org/disease/myotonia-congenita