Myotonia Congenita (MC) is a rare inherited neuromuscular disorder in which the muscles are not able to relax after contraction. This results in muscle stiffness, which hinders movement. It is a neuromuscular channelopathy that affects Chloride channels.1Lossin C, George AL Jr. Myotonia congenita. Adv Genet. 2008;63:25-55. doi: 10.1016/S0065-2660(08)01002-X. PMID: 19185184. These channels are located on the muscle cell membrane, known as the sarcolemma. It’s important to note that the condition generally preserves the intact structure of muscle fibers. MC usually presents in early childhood.
What Are The Types of Myotonia Congenita?
There are two types of the disease: Becker’s disease and Thompsen’s disease.
Becker’s disease:
It has an autosomal recessive inheritance pattern and is more severe. Hence, For Becker’s disease, the child must inherit the defective gene from both parents. However, it is the more common variant. Symptoms in Becker’s appear at around four years of age. These patients have repeated attacks of severe muscle weakness.
Thomsen’s disease:
It is an autosomal dominant condition and is considered milder. Hence, Thomsen’s disease occurs when the child inherits the defective gene from only one parent. Research has shown that Thomsen is rarer, and symptoms appear earlier in childhood, relative to Becker.2Sun C, Tranebjaerg L, Torbergsen T, Holmgren G, Van Ghelue M. Spectrum of CLCN1 mutations in patients with myotonia congenita in Northern Scandinavia. Eur J Hum Genet. 2001 Dec;9(12):903-9. doi: 10.1038/sj.ejhg.5200736. Erratum in: Eur J Hum Genet. 2010 Feb;18(2):264. PMID: 11840191.
What Is The Cause Of Myotonia Congenita?
Myotonia Congenita happens because of mutations in the CLCN1 gene.3Conravey A, Santana-Gould L. Myotonia congenita and myotonic dystrophy: surveillance and management. Curr Treat Options Neurol. 2010 Jan;12(1):16-28. doi: 10.1007/s11940-009-0055-z. PMID: 20842486. The CLCN1 gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. This leads to a problem with the muscle Cl- channel called CIC-1. These channels are important for muscle function, nerve communication (neurotransmitter release), and ion movement.
Mutations in the CLCN1 gene alter the usual structure or function of chloride channels. The altered channels cannot properly regulate ion flow, reducing the movement of chloride ions into skeletal muscle cells. This disruption in chloride ion flow triggers prolonged muscle contractions, which are the hallmarks of myotonia.
The faulty channels inhibit the passage of chloride ions through the muscle cell membrane. This makes the muscle membrane overexcitable, which results in repetitive depolarization and myotonia.
How Common is Myotonia Congenita?
Globally, the frequency of MC is around 1 for every 100,000 people. Thompsen MC occurs in 1 out of every 23,000 people. Becker’s disease occurs in 1 out of every 50,000 people.
Both types of MC are more frequent in Scandinavian countries, where the prevalence is 1 in 10,000. This prevalence is ten times higher than the estimated worldwide occurrence. Males tend to have more severe symptoms.4 Emery AE. Population frequencies of inherited neuromuscular diseases–a world survey. Neuromuscul Disord. 1991;1(1):19-29. doi: 10.1016/0960-8966(91)90039-u. PMID: 1822774. However, women may experience more severe symptoms during pregnancy and menstruation.
What Are The Symptoms of Myotonia Congenita?
Generally, Myotonia Congenita characterizes individuals with difficulty in relaxing muscles after contracting.
Symptoms of Thomsen’s start earlier than Becker’s. Clinical signs for Thomsen generally affect the arms and face. Symptoms of Becker start at the lower extremities.
Symptoms in children may include:
- Problems in chewing, speaking, and swallowing food. The swallowed food may also get stuck and result in choking, gagging, and reflux.
- Problems in balance and coordination due to clumsiness and double vision.
- Muscle stiffness, cramps, and weakness may also be present. For example, a child may present with difficulty opening eyes after prolonged crying.
- Repetitive movements or exercise that temporarily relieves muscle stiffness. This is known as the “warm-up phenomenon.”
Becker’s disease also has a more athletic appearance than Thomsen’s due to more muscle hypertrophy. This is especially noticeable in the large muscle groups of the lower limbs.5Lakraj AA, Miller G, Vortmeyer AO, Khokhar B, Nowak RJ, DiCapua DB. Novel mutations in the CLCN1 gene of myotonia congenita: 2 case reports. Yale J Biol Med. 2013 Mar;86(1):101-6. Epub 2013 Mar 12. PMID: 23483815; PMCID: PMC3584487.6Dunø M, Colding-Jørgensen E, Grunnet M, Jespersen T, Vissing J, Schwartz M. Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype. Eur J Hum Genet. 2004 Sep;12(9):738-43.
How Is Myotonia Congenita Diagnosed?
Healthcare providers typically diagnose Myotonia Congenita during childhood. They may inquire about symptoms and family history, as well as conduct a physical examination to test for muscle stiffness. The exams generally include:
- Rapid opening and closing of the patient’s eyes. Additionally, repeated tapping of a muscle induces myotonia.7Hahn C, Salajegheh MK. Myotonic disorders: A review article. Iran J Neurol. 2016 Jan 05;15(1):46-53.
- Assessing patient’s grip release time. This can involve asking the patient to clench and open their fist.
- Superficial and deep reflexes.
If the physician suspects Myotonia Congenita, then the following tests may be ordered.
- Blood testing: Blood is tested for elevated levels of CK MB. Muscle cells release CK MB due to excessive use. Myotonia Congenita has exhibited levels three to four times higher than normal.
- Electromyography(EMG): An electromyogram measures electronic discharges of muscles. It can be used to differentiate between nerve conduction disorders and muscle disorders. However, it cannot differentiate between different channelopathies. Myotonia congenita may show diffuse electronic discharges and spontaneous activity.
- Muscle Biopsy: Rarely performed, a muscle biopsy involves examining a muscle tissue sample under a microscope. Myotonia congenita may present with heterogeneous muscle fibers, the absence of type 2B fibers, and the presence of multiple nuclei.
- Genetic testing: Genetic testing is considered the gold standard for diagnosis. Initially, the laboratory performs a multigene panel, which includes CLCN1 and other relevant genes. If the multigene panel does not identify a causal mutation, the laboratory may employ more comprehensive genomic methods such as exome sequencing and mitochondrial sequencing.
How Is Myotonia Congenita Treated?
Treatment generally revolves around physiotherapy. This is to ensure muscle function maintenance. Doctors may prescribe pharmacological treatments that block sodium channels in muscles. Mexiletine is commonly used for this purpose. However, the QT interval must be monitored by ECG during use. It is associated with tremors, dizziness, and ataxia.8Hoffman EP, Kaminski HJ. Mexiletine for treatment of myotonia: a trial triumph for rare disease networks. JAMA. 2012 Oct 3;308(13):1377-8. doi: 10.1001/jama.2012.12906. PMID: 23032555; PMCID: PMC4352340.
Lifestyle modifications can help reduce morbidity. These include avoiding known triggers such as stress and cold temperatures and engaging in regular exercise, which can temporarily alleviate symptoms. Adjustments in diet to include foods that are easier to swallow may also help reduce the risk of choking.
What Is The Outlook Of Myotonia Congenita?
The condition doesn’t worsen over time. Patients suffering from the disorder can expect to live a full, healthy life. Becker’s disease may cause lifelong muscle weakness. However, patients thinking of becoming pregnant should consult a specialist for genetic counseling.
Conclusion
In conclusion, Myotonia Congenita, while a rare genetic disorder with different manifestations in its two types, can be managed with a combination of medical interventions, physiotherapy, and lifestyle adjustments. Early diagnosis and appropriate treatment can significantly improve the quality of life for individuals affected by this condition. While challenges may exist, especially in the case of Becker’s disease, many individuals with Myotonia Congenita can lead fulfilling lives with proper care and support.
Refrences
- 1Lossin C, George AL Jr. Myotonia congenita. Adv Genet. 2008;63:25-55. doi: 10.1016/S0065-2660(08)01002-X. PMID: 19185184.
- 2Sun C, Tranebjaerg L, Torbergsen T, Holmgren G, Van Ghelue M. Spectrum of CLCN1 mutations in patients with myotonia congenita in Northern Scandinavia. Eur J Hum Genet. 2001 Dec;9(12):903-9. doi: 10.1038/sj.ejhg.5200736. Erratum in: Eur J Hum Genet. 2010 Feb;18(2):264. PMID: 11840191.
- 3Conravey A, Santana-Gould L. Myotonia congenita and myotonic dystrophy: surveillance and management. Curr Treat Options Neurol. 2010 Jan;12(1):16-28. doi: 10.1007/s11940-009-0055-z. PMID: 20842486.
- 4Emery AE. Population frequencies of inherited neuromuscular diseases–a world survey. Neuromuscul Disord. 1991;1(1):19-29. doi: 10.1016/0960-8966(91)90039-u. PMID: 1822774.
- 5Lakraj AA, Miller G, Vortmeyer AO, Khokhar B, Nowak RJ, DiCapua DB. Novel mutations in the CLCN1 gene of myotonia congenita: 2 case reports. Yale J Biol Med. 2013 Mar;86(1):101-6. Epub 2013 Mar 12. PMID: 23483815; PMCID: PMC3584487.
- 6Dunø M, Colding-Jørgensen E, Grunnet M, Jespersen T, Vissing J, Schwartz M. Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype. Eur J Hum Genet. 2004 Sep;12(9):738-43.
- 7Hahn C, Salajegheh MK. Myotonic disorders: A review article. Iran J Neurol. 2016 Jan 05;15(1):46-53.
- 8Hoffman EP, Kaminski HJ. Mexiletine for treatment of myotonia: a trial triumph for rare disease networks. JAMA. 2012 Oct 3;308(13):1377-8. doi: 10.1001/jama.2012.12906. PMID: 23032555; PMCID: PMC4352340.
