The two types of myotonia congenita share clinical similarities but also have few differences.

Thomsen

Symptoms of this form become apparent in infancy or toddler ages. The features are not progressive. The degree of severity can differ from one family member to another while males have a more serious clinical picture. Also, it is thought that cool temperatures may exacerbate symptoms in these patients.

This disease predominantly affects the muscles of the legs, hands and/ or eyelids [7]. These individuals experience challenges with releasing of a hand grip, walking, running, and transitioning from lying or sitting positions to standing.

Further characteristics of the disease include spasms of muscles such as those of the face, trunk, and other parts of the body. When the extraocular muscles are involved, the patients develop acute episodes of diplopia or strabismus. Also, myotonia of the throat muscles causes trouble with swallowing, chewing and speaking following a period of rest.

On physical exam, the patients will likely have normal muscle strength and little to none weakness.

Becker

The symptoms associated with the Becker variant become visible between the ages of 4 to 12 years old. However, there have been later onset cases reported. This disease is progressive and more severe, which is in contrast to the Thomsen type. Another difference from the other form is that cold exposure does not worsen symptoms.

These patients initially experience myotonia in the leg muscles, but the disease eventually progresses to involve the arms, trunk, and face [8].

On the physical examination, there is profound hypertrophy, and therefore, the individuals typically present with the "body-builder" physical appearance. They tend to exhibit muscle hypertrophy. Also, muscle weakness may be seen in such patients.

• Hemophilia A

  ENLARGEMENT (GINGIVAL OVER GROWTH, GUM HYPERTROPHY) GLYCOGEN STORAGE DISEASE (GSD) GRANULOMA GYNECOMASTIA GUM HYPERTROPHY (see GINGIVAL ENLARGEMENT) H HAND-FOOT-AND-MOUTH DISEASE HEMANGIOMAS AND CAPILLARY VASCULAR MALFORMATIONS HEMATOMA HEMIHYPERTROPHY HEMOPHILIA [euro-libris.ro]

• Weakness

  People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. [ghr.nlm.nih.gov]

  There is no weakness in Thomsen disease, but Becker disease is associated with transient weakness after prolonged rest and sometimes with progressive weakness. [msdmanuals.com]

  Nineteen had transient weakness. In the upper extremities, onset age of transient weakness was usually in the early teens. [ncbi.nlm.nih.gov]

  […] by a marked worsening of myotonia by cold and by the presence of clear episodes of weakness; Group 2 Sodium channel myotonia—notable for the absence of episodic weakness but may have cold sensitivity. [medscape.com]

  Episodes of weakness or paresis that do not necessarily coincide with exposure to cold temperatures or myotonia may occur. Weakness may be induced by administration of potassium. The disorder is not associated with muscle wasting or hypertrophy. [accessanesthesiology.mhmedical.com]

• Pain

  Children start off by experiencing mild bouts of pain and muscle stiffness. The pain can remain at a low level. However, myotonia congenita can be as severe and interfere with any type of movement. [sites.psu.edu]

  If propofol is used, prevention of pain on injection is mandatory because pain can induce a myotonic reaction of the limb or even of the whole body. Neither regional anesthesia nor muscle relaxation can control myotonic contractions. [accessanesthesiology.mhmedical.com]

  We present a family with dominantly inherited myotonia congenita and painful, electrically silent muscle contractions after exertion. [ncbi.nlm.nih.gov]

  Injections that might cause pain and the use of volatile anesthetic agents and depolarizing muscle relaxants are contraindicated as their use can precipitate a myotonic crisis. [doi.org]

• Fatigue

  Episodes of prolonged muscle contraction in those with Thomsen disease can also result in subsequent muscle weakness or fatigue. [manchesterneurophysio.co.uk]

  Identifier NOVEL_Cogan_28-11 Title Myopathies - Myotonia Congenita (Thomsen) Subject Eye Movement Recordings; Myopathies, Congenital; Lid Lag; Thomsen Disease History Presenting Symptom: lid lag reminiscent of fatigue. 28 year old man; chief complaint [collections.lib.utah.edu]

  Westerblad, Skeletal Muscle Fatigue: Cellular Mechanisms, Physiological Reviews, 88, 1, (287), (2008). Gregg D. [doi.org]

  The prolonged recovery of excitability following sustained muscle contraction is likely to be a contributing factor to symptoms of weakness and fatigue experienced by RMC patients. [ncbi.nlm.nih.gov]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 14, 2019 [patientslikeme.com]

• Falling

  Patients having myotonia congenita often are the ones who fall due to hasty movements as they get more prone to such disability due to the inability of stabilizing themselves which causes them to lose balance. [samrx.com]

  Close monitoring for falls is crucial if M.N.’s healthcare team does decide to initiate these in the future. [raftpubs.com]

  However, a fall into cold water may render the person unable to move for the duration of submergence. As with myotonic goats, children are more prone to falling than adults, due to their impulsivity. [en.wikipedia.org]

  Case 1 Frequent falls and difficulty walking appeared in the older brother at four years of age. [dovepress.com]

  Early symptoms may include: Difficulty swallowing Gagging Stiff movements that improve when they are repeated Shortness of breath or tightening of the chest at the beginning of exercise Frequent falls Difficulty opening eyes after forcing them closed [nlm.nih.gov]

• Difficulty Getting Out of Bed

  Now after 18 months of therapy these children have no difficulty getting out of bed in the morning; the difficulty in releasing grip and in initiating walking is mild; the girl no longer falls while walking; but the difficulty in climbing stairs persists [indianpediatrics.net]

• Dysphagia

  […] congenita, see there; also known as Thomsen disease. myotonia congenita Thomsen's disease Neurology An AD or AR condition characterized by deficiency of true cholinesterase Clinical Inability of muscles to relax quickly, resulting in myotonia, gagging, dysphagia [medical-dictionary.thefreedictionary.com]

  Other clinical signs were excitement-induced upper airway stridor and oropharyngeal dysphagia. [nmd-journal.com]

  […] hypertrophy Increased skeletal muscle cells 0003712 Percent of people who have these symptoms is not available through HPO Autosomal dominant inheritance 0000006 Autosomal recessive inheritance 0000007 Childhood onset Symptoms begin in childhood 0011463 Dysphagia [rarediseases.info.nih.gov]

• Gagging

  Early symptoms may include: Difficulty swallowing Gagging Stiff movements that improve when they are repeated Shortness of breath or tightening of the chest at the beginning of exercise Frequent falls Difficulty opening eyes after forcing them closed [nlm.nih.gov]

  Early symptoms in a child may include: Gagging Difficulty swallowing Stiff movements that improve when they are repeated Possible complications may include: Aspiration pneumonia (caused by swallowing difficulties) Frequent choking or gagging in infants [blouw.moneomed.com]

• Muscle Rigidity

  Other case reports of diffuse muscle rigidity with no signs of rhabdomyolysis following succinylcholine have been published. [accessanesthesiology.mhmedical.com]

  Affected individuals have difficulty relaxing certain muscles after contracting them (myotonia), muscle stiffness (rigidity), and associated symptoms. Such symptoms tend to occur when attempting to move certain muscles after rest. [mda.org.au]

  We report a family in which two sisters with myotonia congenita (MyC) were referred for malignant hyperthermia (MH) evaluation after each developed muscle rigidity with anesthesia. [ncbi.nlm.nih.gov]

  In the two sisters described, exposure to succinylcholine resulted in generalized muscle rigidity without a rise in body temperature. [rarediseases.org]

• Choking

  Complications may include: Aspiration pneumonia caused by swallowing difficulties Frequent choking, gagging, or trouble swallowing in an infant Long-term (chronic) joint problems Weakness of the abdominal muscles Call your provider if your child has symptoms [nlm.nih.gov]

  Early symptoms in a child may include: Gagging Difficulty swallowing Stiff movements that improve when they are repeated Possible complications may include: Aspiration pneumonia (caused by swallowing difficulties) Frequent choking or gagging in infants [blouw.moneomed.com]

• Masseter Spasm

  The clinical picture can range from severe myotonic reactions (e.g., masseter spasm, opisthotonus) to attacks of weakness and paralysis. [experts.umn.edu]

  Symptoms include delayed relaxation of the muscles after voluntary contraction (myotonia), and may also include stiffness, hypertrophy (enlargement), transient weakness in some forms of the disorder (from certain genetic mutations), severe masseter spasm [dbpedia.org]

  However, depolarizing muscle relaxants must be avoided because they may cause exaggerated contracture, masseter spasm, and laryngospasm, thus complicating extubation [3, 7]. [link.springer.com]

• Myopathy

  Myopathy Myopathy may develop in some patients with non-dystrophic myotonia (Becker, 1977; Plassart et al., 1996; Nagamitsu et al., 2000). [medscape.com]

  Other rare myopathies include autophagic vacuolar myopathy, cap disease, congenital myopathy with arrest of myogenesis, myosin storage (hyaline body) myopathy and zebra body myopathy. [mayoclinic.org]

  Myopathies - Myotonia Congenita (Thomsen) Your browser does not support the video tag. [collections.lib.utah.edu]

  Heterozygotes are often asymptomatic but for some mutations heterozygosity is sufficient to cause pronounced myotonia, although without weakness and myopathy. [ncbi.nlm.nih.gov]

  G71.20 Congenital myopathy, unspecified G71.22 Centronuclear myopathy G71.220 X-linked myotubular myopathy G71.228 Other centronuclear myopathy G71.29 Other congenital myopathy Reimbursement claims with a date of service on or after October 1, 2015 require [icd10data.com]

• Myalgia

  Early reports suggested that patients with myoadenylate deaminase deficiency had various forms of myalgia, and exercise intolerance. [ncbi.nlm.nih.gov]

• Muscle Cramp

  A sporadic Japanese case of myotonia congenita with painful muscle cramps is reported. [ncbi.nlm.nih.gov]

  Myotonia congenita can also increase the size of your muscles and cause muscle cramping. Myotonia congenita affects the chloride channels on your muscle membrane. [my.clevelandclinic.org]

  Myotonia congenita symptoms can include muscle stiffness and muscle weakness. It also includes muscle weakness during movement after rest, which is called myotonia. Myotonia causes muscle cramps and pain in some people. [webmd.com]

  DISCUSSION In 1978, Fishbein et al. described MAD deficiency in skeletal muscle of 5 patients with exercise-related muscle cramps, and myalgias2. [scielo.br]

• Muscle Spasm

  We describe a previously healthy 32-year-old woman who developed a life-threatening muscle spasm and secondary ventilation difficulties following a preoperative injection of suxamethonium. [ncbi.nlm.nih.gov]

  […] tone, frequently including muscle spasm or rigidity [...] [collinsdictionary.com]

  Symptoms may include the following: Abnormal enlargement of muscles Muscle stiffness or rigidity Difficulty with walking or running, getting up from a seat, or loosening the handgrip Muscle spasms in the face or other body parts Temporary double vision [webmd.com]

  Affected dogs usually present with non-painful muscle spasms, stridor, dyspnea, dysphonia, stiff-stilted gait, bunny-hopping and collapse associated with exercise and activity. [vetbook.org]

  Myotonia Congenita is a hereditary disorder affecting the tone and contraction of skeletal muscle. The characteristic symptom of Myotonia Congenita is muscle spasm whereby muscles are unable to relax quickly after contracting. [scirp.org]

• Long Arm

  The reason for these processes lies in the CLCN1 gene mutations, located on the long arm of chromosome 7 (7q35). This gene encodes an essential for normal function of skeletal muscle cells protein. [ivami.com]

  Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. Therefore, “7q35” refers to band 35 on the long arm of chromosome 7. [rarediseases.org]

• Strabismus

  To determine the genetic basis of myotonia congenita (MC) and strabismus in a large Caucasian family. Seven patients making up four generations of a family with MC and strabismus were recruited. [ncbi.nlm.nih.gov]

  Ophthalmic history and exam revealed eyelid myotonia and strabismus. Age of onset with strabismus was between 3-6 year old. Sequencing results revealed a c. 1333G>A; p. Val445Met mutation in the SCN4A gene in all affected patients. [iovs.arvojournals.org]

  When the extraocular muscles are involved, the patients develop acute episodes of diplopia or strabismus. Also, myotonia of the throat muscles causes trouble with swallowing, chewing and speaking following a period of rest. [symptoma.com]

  Multiple cases of bilateral adduction restriction have been reported, as well as those with divergent strabismus and convergence paralysis. The abducting eye does not present with nystagmus. [eyewiki.aao.org]

  For example, involvement of muscles that control movements of the eyeballs (extraocular muscles) may lead to temporary episodes of double vision or abnormal deviation of one eye in relation to the other (strabismus). [rarediseases.org]

• Diplopia

  When the extraocular muscles are involved, the patients develop acute episodes of diplopia or strabismus. Also, myotonia of the throat muscles causes trouble with swallowing, chewing and speaking following a period of rest. [symptoma.com]

  Aggarwal PGY 4 Neurology 2 Teen aged male admitted with acute onset generalized weakness for 1 day duration Woke up with diffuse weakness; no anti gravity strength in arms, unable to get out of bed Proximal > distal weakness; bilaterally symmetrical Denied diplopia [slideplayer.com]

• Paresis

  Ouabain infusion did not affect the recovery from transient paresis or the accompanying electromyographic changes, indicating that the warming-up phenomenon in generalized myotonia is not mediated by Na(+)-K(+)-ATPase. [ncbi.nlm.nih.gov]

• Seizure

  الصفحة 68 - Provisional Committee on Quality Improvement, Subcommittee on Febrile Seizures. Practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. ‏ الصفحة 196 - Absence seizures. In: Wyllie E, ed. [books.google.com]

  He is currently responding well to levetiracetam and has not suffered a seizure since its initiation. [raftpubs.com]

  The patient, a 24-years old man, an adoptive son without data about his relatives, showed, at the age of 8 months, difficulty in opening hands after grasp and a history of generalized seizures since he was 1-year old. [moh-it.pure.elsevier.com]

  He was prescribed calcium replacement and the anticonvulsant was withheld with no more episodes of seizure. [ncbi.nlm.nih.gov]

  […] for depression: nefazodone for HIV: nelfinavir (Viracept), ritonavir (Norvir), lopinavir and ritonavir (Kaletra), indinavir (Crixivan), saquinavir (Invirase). for tuberculosis (TB): rifampin (Rifadin), rifabutin (Mycobutin), rifapentine (Priftin) for seizures [clinicaltrials.gov]

• Clumsiness

  Parents describe weakness or clumsiness in their children, as well as stiffness. Myotonic symptoms lessen with age but do not disappear, and they are most noticeable after a period of rest. [msdmanuals.com]

  I was called clumsy, lazy, and a hypochondriac. Once we asked a family physician why I was having so much trouble swallowing, and he said I had "Eve's Curse"... a little bit of the forbidden fruit stuck in my throat. [myotoniacongenita.org]

  Clumsiness and frequent falls. Difficulty chewing, swallowing (dysphagia) or talking. Double vision or a lazy eye. Enlarged muscles (hypertrophy), leading to an athletic appearance. [my.clevelandclinic.org]

  Children may appear clumsy and fall frequently, even after walking is established. Patients may also exhibit difficulty in opening eyes during prolonged contraction, such as crying. [ncbi.nlm.nih.gov]

• Dysarthria

  Case Report We describe the case of a 33-year-old patient of Scandinavian background who was diagnosed with MC at age of 12 when she presented with dysarthria. [jcgo.org]

  Teen aged male admitted with acute onset generalized weakness for 1 day duration Woke up with diffuse weakness; no anti gravity strength in arms, unable to get out of bed Proximal > distal weakness; bilaterally symmetrical Denied diplopia, dysphagia, dysarthria [slideplayer.com]

  Orofacial strength, dysarthria, and dysphagia in congenital myotonic dystrophy. Muscle Nerve 2018;58(3):413-7. PMID 29901230 09 Bossen EH, Shelbourne JD, Verkauf BS. Respiratory muscle involvement in infantile myotonic dystrophy. [medlink.com]

  Periodic paralysis was not associated with dyspnea or dysarthria. Her father (V: 7) was definitively diagnosed with hypokalemic periodic paralysis in his twenties. Her mother (V: 6) suffered from myotonia and muscle hypertrophy from childhood. [journals.plos.org]

  Especially orbicularis oris Clinical test Opposition of lips Ask patient to pucker lips Functional changes Eyes: Often early in disease course Lid closure: Incomplete Sleeping: With eyes open Bulbar dysfunction Using straws Blowing up balloons Speech: Dysarthria [neuromuscular.wustl.edu]

• Neonatal Hypotonia

  Diagnostic profile of neonatal hypotonia: an 11-year study. Pediatr Neurol. 2001; 25:32–37. 20. Kim ES, Jung KE, Kim SD, Kim EK, Chae JH, Kim HS, et al. [synapse.koreamed.org]

The evaluation of the patient includes a thorough personal and family history along with a comprehensive physical exam. The workup further consists of specialized studies.

Genetic counseling

The clinician should offer genetic counseling to the family members and the patients themselves when of appropriate age. Genetic testing may be an option as well. However, since certain mutations are implicated in both dominant and recessive traits, special consideration should be applied while interpreting the molecular analysis [9].

Physical exam

The physical exam reveals characteristic findings such as difficulty with relaxing a hand grip following the closing of the hand. Also, another positive clinical test is percussion myotonia, which is the persistent contraction that results after tapping the muscle.

Electromyography

This test will confirm the diagnosis. An EMG records the electrical activity of the skeletal muscle during rest and contraction [10]. Specifically, the results are characterized by repetitive action potentials which develop after myotonic discharges or forceful contractions.

Of note, asymptomatic Becker disease carriers will also demonstrate myotonic discharges. This is especially observed in males.

Muscle biopsy

Some patients will be assessed with muscle biopsy, in which a sample of skeletal muscle tissue is obtained and submitted for analysis. The results reveal hypertrophic changes.

Other

Additional studies may be performed to exclude similar diseases and to help confirm the diagnosis of myotonia congenita.

Finally, there is a rare study in which a sample of the muscle tissue is exposed to halothane. This in vitro testing will show a contracture response that mimics a picture similar to that of malignant hyperthermia.

• Hypercapnia

  Ventilatory response to carbon dioxide is reduced and chronic hypercapnia is a common finding.(c)Cardiac: Conduction defects are common in patients with DM [31]. [hindawi.com]

  Hormone (FSH) may be increased Growth hormone: Reduced release Insulin resistance Pregnancy: Frequent fetal loss & major complications Insulin-like growth factor-1 (IGF-1): Reduced Hypertriglyceridemia (67%) Respiratory Reduced response to hypoxia; Hypercapnia [neuromuscular.wustl.edu]

The therapeutic approach of myotonia congenita will depend on the overall clinical picture, which varies from one patient to another.

The management of this disorder may involve pediatricians, orthopedists, physical and occupation therapists, psychologists, and other professionals to assist in social and vocational services. Furthermore, early intervention can allow the patients to overcome the symptoms.

Medications

The treatment for both types is usually symptomatic and supportive especially in those with stiffness and cramping. Studies have shown that stabilizers of the skeletal muscle membranes are the superior drugs. The myotonic features are treated with antiseizure medications such as carbamazepine, phenytoin [11], and acetazolamide [12].

Additionally, muscle relaxants may be helpful; these include dantrolene sodium and quinine sulfate. A sodium channel inhibitor called mexiletine may be used. Finally, the antihistamine, trimeprazine, can be beneficial. Since all of these medications are associated with side effects, the clinician should weigh the risks and benefits.

Other

Physical therapy techniques are essential as well. Certain exercises using the affected muscles can loosen the rigidity and stiffness.

Genetic counseling is important for patients and their family members. They should be provided with information on modes of transmission, the probability of having affected and carrier offspring, and other details as well.

Myotonia congenita is not a progressive disease. These patients are not associated with significant morbidity. In fact, their quality of life is excellent as individuals lead productive lives and even play strength demanding sports. Furthermore, they also have a normal life expectancy.

In Thomsen disease, the inheritance pattern is autosomal dominant [3], while the Becker form is transmitted through an autosomal recessive trait [4]. The identified mutations are in the CLCN1 gene, which plays a pivotal role in the function of chloride ion channels.

Both variants are referred to as "ion channel diseases" since they emerge from the abnormal conductance of ions across the cell membranes of the skeletal muscles [5].

The estimated prevalence of myotonia congenita ranges from 1 to 10 per population of 100,000. Also, the onset can occur in infancy, early childhood, or even adulthood. If this disease manifests in early infancy, typically the family members recognize the abnormalities in the patient.

Both Thomsen and Becker myotonia congenita are associated with mutations in the CLCN1 gene. The mutations are located on the long arm of chromosome 7 (7q35) [6]. CLCN1 is a gene that plays a role in the function of chloride ion channels in the cell membranes of skeletal muscles.

The chloride channels are responsible for the regulation of the electric excitability of the cell membranes. Hence, a defect in the CLCN1 gene will diminish the numbers of the channels and/or affect their function. These changes lead to decreased chloride flow and the resultant electrical instability accounts for the findings observed in myotonia congenita.

The sodium channel may also be involved in the pathogenesis of this disease. It is thought to participate in the hyperexcitability of the muscles seen with myotonia congenita.

Since myotonia congenita is a genetic disease, it cannot be prevented. However, patients and family members can seek genetic counseling and receive education to guide them in family planning. Moreover, they may be offered prenatal genetic testing as well.

Myotonia congenita is an inherited disorder in which involved skeletal muscles cannot relax after hyperexcitability or an enhanced response to a stimulus. The mutations responsible for this condition are found in the CLCN1 gene, which has two modes of transmission- autosomal dominant or autosomal recessive. Additionally, there are two forms of the condition: Thomsen disease [1], which is autosomal dominant, and Becker disease [2], which is autosomal recessive.

This rare disorder presents in early infancy, early childhood, or slightly later depending on the type. The symptoms are myotonia and rigidity, along with other associated features. Additionally, patients may experience difficulty with moving affected muscles following a period of rest. With regards to appearance, individuals may exhibit enlargement of the muscles and resemble a "herculean" appearance.

The diagnosis is achieved through assessment of the patient's personal and family history, key observations on physical examination, and specific findings on the electromyogram (EMG). Further studies may be warranted to exclude similar diseases.

The therapeutic approach is usually symptomatic and supportive as there are medications that can help alleviate the myotonia and stiffness. Other important components in the treatment involve physical exercises.

Overall, the prognosis of myotonia congenita is generally good.

Myotonia congenita is an inherited disorder that affects the relaxation of skeletal muscle cells. This occurs because of a mutation, or a change in the gene that controls the function of specific proteins that allow ions to travel across the cells. Symptoms may appear during the first few months, early childhood, or early adulthood.

Causes

There are two forms of this condition, and each one is inherited differently. One type is known as Thomsen myotonia congenital which is autosomal dominant. The other type is the Becker myotonia congenita, which is inherited in an autosomal recessive pattern.

Symptoms

The main symptom is that the skeletal muscles cannot relax quickly after the episode of contraction. This is observed when the patients cannot pull their hand right away after a handshake. It is a slow process to relax the muscle. Since the muscles have difficulty relaxing, this results in the stiffness known as myotonia.

Patients may also have difficulty with activities like walking, running, or changing positions. They may experience trouble with chewing, swallowing and talking. Some patients may suffer from shortness of breath or chest tightness at the beginning of the physical exercise.

Diagnosis

The steps in diagnosis include taking detailed personal and family history, physical exam, and an electromyogram. For example, the clinician tests the patient by assessing whether the patient can release the grip quickly after closing his or her hand. Also, the doctor may tap a muscle and check for a prolonged contraction.

The electromyogram tests the electrical impulses from the affected muscles. The abnormal repetitive impulses can confirm this disease.

Note that these patients may have a "body builder" type of body with enlarged muscles.

Treatment

Treatment of myotonia congenita involves a multidisciplinary approach that consists of pediatricians, orthopedics, physical therapists, and other healthcare professionals. The earlier the intervention, the better for the children.

Specific drug therapies aim to relieve the symptoms such as stiffness and cramping. For example, muscle relaxants and anticonvulsants can be useful. Phenytoin, quinine, and mexiletine are the examples of drugs commonly prescribed for this condition .

Special physical exercises are recommended to help relieve stiffness in these patients.

Note that individuals affected with myotonia congenita can lead a relatively normal life. They also have a normal life expectancy.

1. Thomsen J. Tonische Krampfe in willkurlich beweglichen Muskeln in Folge von ererbter psychischer Disposition. Arch Psychiatr Nervenkrankheiten. 1876; 6: 702–18.
2. Becker PE. Myotonia congenita and syndromes associated with myotonia Stuttgart: Georg Thieme Verlag. 1977.
3. Ptacek LJ, Johnson KJ, Griggs RC. Genetics and physiology of the myotonic muscle disorders. N Engl J Med. 1993; 328:482–489.
4. Fialho D, Schorge S, Pucovska U, et al. Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions. Brain. 2007; 130(Pt 12): 3265–74.
5. Steinmeyer K, Ortland C, Jentsch TJ. Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel. Nature. 1991; 354(6351): 301–304.
6. Jurkat-Rott K, Lerche H, Lehmann-Horn F. Skeletal muscle channelopathies. J Neurol. 2002; 249(11):1493–1502.
7. Wakeman B, Babu D, Tarleton J, et al. Extraocular muscle hypertrophy in myotonia congenita. J AAPOS. 2008; 12 (3): 294–6.
8. Becker PE, Knussmann R, Kühn E. Myotonia congenita and syndromes associated with myotonia: clinical-genetic studies of the nondystrophic myotonias. Thieme. 1977; ISBN 978-3-13-224801-4.
9. Dutzler R, Campbell EB, Cadene M, et al. X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity. Nature. 2002; 415(6869): 287–294.
10. Fournier E, Viala K, Gervais H, et al. Cold extends electromyography distinction between ion channel mutations causing myotonia. Ann Neurol. 2006; 60(3): 356-365.
11. Aichele R, Paik H, Heller AH. Efficacy of phenytoin, procainamide, and tocainide in murine genetic myotonia. ‎Exp Neurol. 1985; 87(2): 377–81.
12. Trudell RG, Kaiser KK, Griggs RC. Acetazolamide-responsive myotonia congenita. Neurology. 1987; 37(3): 488–91.