This is part of Rare diseases.
Diagnosis: Congenital myotonia
Synonyms: Myotonia congenita, Thomsen disease, Becker myotonia
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Date of publication: 2010-07-01
Version: 3.0
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Congenital myotonia is an inherited form of muscle stiffness. The disease presents as attacks of muscle stiffness brought on by physical activity immediately after a period of rest. In some cases the stiffness is accompanied by temporary muscle weakness. There are two types of congenital myotonia: Thomsen disease and Becker myotonia.
The disorder was first described in 1876 by the Danish physician Julius Thomsen. He was affected by the condition himself, as were more than twenty of his relatives over several generations. In 1971, the German physician Peter Emil Becker described a variant of congenital myotonia distinguished by more severe symptoms and with a different inheritance pattern.
International medical literature indicates that congenital myotonia affects about 6 individuals per 100,000 population. This means that there are probably over 500 individuals with congenital myotonia in Sweden, although many have not yet received an accurate diagnosis. Becker myotonia is about twice as common as Thomsen disease.
Congenital myotonia is caused by a mutation in a gene which controls the production of (codes for) one of the proteins which makes up the muscle’s chloride ion channel. Gene CLCN is located on chromosome 7 (7q35). The chloride ion channel can be described as a pore consisting of two matching sub-units and is found in the membrane of muscle fibres. This pore normally opens to allow electrically charged chloride ions to pass through into the cell after a muscle contraction. It is essential that chloride ions flow rapidly through the pore in order to restore and maintain the difference in electric charge between the outside and inside of the cell. If the function of the chloride channel is impaired the muscle is not able to relax, leading to stiffness. More than 100 mutations to gene CLCN1 have been identified. Different mutations result in different inheritance patterns and varying degrees of severity of the disease.
The inheritance pattern of Thomsen disease is autosomal dominant, while Becker myotonia is an autosomal recessive disorder.
The inheritance pattern of Thomsen disease is autosomal dominant. This means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disorder and do not pass it on.
The inheritance pattern of Becker myotonia is autosomal recessive. This means that both parents are healthy carriers of a mutated gene. When two healthy carriers have a child, there is a 25 per cent risk that the child will inherit two mutated genes (one from each parent) in which case he or she will have the disease. In 50 per cent of cases the child inherits only one mutated gene (from one parent only) and like both parents, will be a healthy carrier of the mutated gene. In 25 per cent of cases the child will not have the disease and will not be a carrier of the mutated gene.
A person with an inherited autosomal recessive disease has two mutated genes. If this person has a child with a person who is not a carrier of the mutated gene, all the children will inherit the mutated gene but they will not have the disorder. If a person with an inherited autosomal recessive disease has children with a healthy carrier of the mutated gene (who has one mutated gene) there is a 50 per cent risk of the child having the disorder, and a 50 per cent risk of the child being a healthy carrier of the mutated gene.
Symptoms in Becker myotonia usually present before the age of 15, and in Thomsen disease in early childhood. The predominant symptom associated with congenital myotonia is muscle stiffness brought on by strenuous exercise immediately after a period of rest. The stiffness is relieved if the individual continues physical activity or “warms up”. In many cases stiffness is accompanied by transient muscle weakness. Sudden loud noises or other unexpected stimuli may trigger severe myotonia and weakness, sometimes even causing the individual to collapse. Muscle stiffness may also be triggered, or aggravated, by exposure to cold, stress, fasting, and fatigue. Muscle strength is usually normal between attacks, although some individuals may experience mild but prolonged weakness of the neck, the lower arms, and the hands. Myotonic stiffness causes the muscles to tense even when the individual is at rest, and as a result the individual may have larger than normal muscles, particularly in the calves, thighs and buttocks. Muscle pain is common. The symptoms of Thomsen disease and Becker myotonia differ slightly.
Thomsen disease presents early (at between one and two years of age) and is not progressive. The symptoms affect all muscles including the face, tongue, and pharynx.
Becker myotonia has a later onset (between the ages of 5 and 15). The symptoms tend to be more severe than in Thomsen disease and the condition may progress slowly until around the age of thirty when it stabilises. The stiffness is most pronounced in the legs, but may gradually spread to the arms and face. A common symptom which distinguishes Becker myotonia is mild muscle atrophy of the arms.
Muscle stiffness may increase as a result of certain medical treatments, such as some asthma medications (beta-agonists), medications used to treat heart problems and high blood pressure (beta-blockers), diuretics, and muscle relaxants sometimes used in surgical procedures.
For reasons as yet unclear, men tend to have more severe symptoms than women. The severity of the disease may vary greatly within the same family. Women commonly experience an aggravation of symptoms during pregnancy. The myotonia is also worse in cases where the metabolism is abnormally slow (hypothyroidism).
The diagnosis is based on typical symptoms and by confirming muscle stiffness (myotonic reaction) in physical activity after rest. An electromyography (EMG), which measures electrical activity in the muscle, will show characteristics of myotonia and exclude other muscle disorders.
A muscle biopsy, a procedure in which a piece of muscle tissue is removed and examined microscopically, is often performed. In congenital myotonia, the muscle biopsy should be normal or display only minor abnormalities.
In 95 per cent of cases, DNA analysis can confirm the diagnosis. Prenatal testing is possible.
There is currently no cure for the disorder. It is important to learn what triggers attacks of myotonic reaction/muscle stiffness. Physical activities should preferably be carried out at an even pace, and should not be interrupted by long breaks. Long periods without food should also be avoided. As myotonic stiffness is relieved by repetitive muscular activity, it is possible to prepare for more strenuous activities by carefully warming up the muscles. Most individuals with the disorder learn to manage muscle stiffness, for example by avoiding exposure to cold. Since stress can induce myotonic reactions, it is important to avoid stressful situations. Contact with a physiotherapist is necessary for advice on the correct approach to physical activities.
Certain medications can reduce muscle stiffness, and many individuals with congenital myotonia use these drugs regularly or periodically. The most effective one is mexiletine. In Sweden the use of this drug requires authorisation by the Swedish Medical Products Agency.
Under general anaesthesia, some medications used to relax muscles (depolarizing muscle relaxants) may trigger severe myotonia and cause breathing difficulties. It is therefore important that the anaesthetist is informed about the disorder well before a planned surgical intervention.
It is important for children with the disease to be in regular contact with a paediatric neurologist as they are growing up. Habilitation is available for those children who need it, and is planned according to their needs, and in collaboration with those close to the child. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. Support and treatment are provided within the medical, educational, psychological, social and technical fields. Measures may include assessments, treatment, assistance with choice of aids, information about disabilities and counselling. They also include information about support offered by the local authority as well as advice on the way accommodation and other environments can be adapted to the child’s needs.
It is helpful to be well-informed about the disorder when making choices about education and what games and sports to participate in. When deciding on a suitable career, it is important to avoid jobs that require physical exertion, for example heavy lifting or strenuous movements, or being outdoors in cold weather. Career guidance is offered by the Swedish National Labour Market Administration. They also carry out occupational assessments and assist in finding suitable workplaces.
Adults with congenital myotonia should be in contact with a neurologist.
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Neurologists and paediatric neurologists at regional and county hospitals can confirm the diagnosis. At university hospitals in Gothenburg, Linköping, and Stockholm there are units which specialize in neuromuscular diagnostics.
Christopher Lindberg, Senior Physician, Neuromuscular Centre, Sahlgrenska University Hospital/Sahlgrenska, SE-413 45 Gothenburg, Sweden. Tel: +46 31-342 10 00, email: christopher.lindberg@vgregion.se.
Björn Lindvall, Senior Physician, the Muscle Centre at Örebro University Hospital, SE-701 85 Örebro, Sweden. Tel: +46 19 602 10 00, email: bjorn.lindvall@orebroll.se.
Associate Professor Göran Solders, Neurology Clinic, Karolinska University Hospital, SE-141 86 Stockholm, Sweden. Tel: +46 8 585 800 00, email: goran.solders@karolinska.se.
Professor Mar Tulinius, The Queen Silvia Childrens’ Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.
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NHR, The Swedish Association for Persons with Neurological Disabilities, St Eriksgatan 44, 4th floor, Stockholm. Mailing address: Box 490 84, SE-100 28 Stockholm, Sweden. Tel: +46 8 677 70 10, fax: +46 8 24 13 15, email: nhr@nhr.se, www.nhr.se.
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An information leaflet on congenital myotonia that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2010-4-18). Address: SE-120 88 Stockholm, Sweden. Tel: +46 8 779 96 66, fax: +46 8 779 96 67, email: socialstyrelsen@strd.se. Postage will be charged for bulk orders.
Becker PE. Genetic approaches to the nosology of muscle disease. Myotonias and similar disorders. Birth defects, original article series 1971; 7: 52-62.
Colding-Jorgensen E. Phenotypic variability in congenital myotonia. Muscle Nerve 2005; 32: 19-34.
Davies NP, Hanna MG. Neurological channelopathies: diagnosis and therapy in the new millenium. Ann Med 1999; 6: 406-420.
Duno M, Coling-Jorgensen E, Grunnet M, Jespesen T, Vissing J, Schwartz M. Difference in allelic expression of the CLCN1 gene and the possible influenze on the congenital myotonia phenotype. Eur J Hum Genet 2004; 12: 738-743.
Farbu E, Softeland E, Bindoff LA. Anaesthetic complications associated with congenital myotonia: case study and comparison with other myotonic disorders. Acta Anaesthesiol Scand 2003; 47: 630-634.
Hakulinen E. Led själv av en form av myotoni (Mannen bakom syndromet: Julius Thomsen). Läkartidningen 1994; 91: 3178-3180.
Heatwole CR, Moxley RT 3rd. The nondystrophic myotonias. Neurotherapeutics 2007; 4: 238-251.
Koty PP, Pegoraro E, Hobson G, Marks HG, Turel A, Flagler D et al. Myotonia and the muscle chloride channel: Dominant mutations show variable penetrance and founder effect. Neurology 1996; 47: 963-968.
Lacomis D, Gonzales JT, Giuliani MJ. Fluctuating clinical myotonia and weakness from Thomsen’s disease occurring only during pregnancies. Clin Neurol Neurosurg 1999; 101: 133-136.
Lossin C, George AL Jr. Congenital myotonia. Adv Genet 2008; 63: 25-55.
Plassart-Scheiss E, Gervais A, Eymard B, Lagueny A, Pouget J, Warter JM et al. Novel muscle chloride channel (CLCN1) mutations in congenital myotonia with various modes of inheritance including incomplete dominance and penetrance. Neurology 1998; 50: 1176-1179.
Sun C, Tranebjaerg L, Torbergsen T, Holmgren G, Van Ghelue M. Spectrum of CLCN1 mutations in patients with congenital myotonia in Northern Scandinavia. Eur J Hum Genet 2001; 12: 903-909.
Thomsen J. Tonische Krämpfe in willkürlich beweglichen Muskeln in Folge von ererbter psychischer Disposition. (Ataxia muscularis?). Archiv für Psychiatrie und Nervenkrankenheiten 1876; 6: 702-718.
Varkey B, Varkey L. Muscle hypertrophy in congenital myotonia. J Neurol Neurosurg Psychiatry 2003; 74: 338.
OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim
search: congenital myotonia, thomsen disease, becker myotonia
GeneReviews (University of Washington)
www.genetests.org (select Genereviews)
search: congenital myotonia
The Swedish Information Centre for Rare Diseases produced and edited this information material.
The medical expert who wrote the draft of this information material is Associate Professor Göran Solders, Karolinska University Hospital in Stockholm.
The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.
An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.
Date of publication: 2010-07-01
Version: 3.0
Publication date of the Swedish version: 2010-04-26
For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.