What is Myotonia Congenita?Myotonia Congenita is a genetic disorder that is characterised by the inability of skeletal muscle to relax after voluntary movement, people with this condition experience periods of sustained muscle tensing.[1] Myotonia effects any skeletal muscle including muscles of the face and tongue, however it occurs most often in the legs.There are two forms of Myotonia Congenita: Becker disease and Thompson disease. Becker disease causes more severe muscle stiffness, particularly in males. Sudden attacks of muscle weakness is often experienced by people with Becker disease.[1] They may also develop mild, permanent muscle weakness over time. In contrast, muscle weakness is not experienced by people with Thomsen disease.
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Figure 2: inheritance pattern of Thomsen disease Figure 3: inheritance pattern of Becker disease
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Currently there are over 130 known mutations that can cause the myotonia congenita, each with their own specifics.[3] Worldwide population prevalence in humans is 1:100,00 [4]. The Becker form of disease, which is the most severe, is inherited in an autosomal recessively manner, meaning both copies of the CLCN1 gene in each cell are mutated. The children of two individuals who are carriers of a the mutated CLCN1 but are unaffected themseleves have a 20% chance of being affected, a 50% chance of being a carrier and a 25% of being unaffected and not a carrier. [] Shown in figure 2 The Thomsen form is inherited in an autosomal dominant manner, which means one copy of the mutated CLCN1 is sufficient to cause the disorder. Each child of an individual with Thomsen form has a 50% chance of inheriting the disease.[] However three cases have reported who were diagnosed with Thomsen's myotonia and proved on genetic testing not to have mutations in the chloride gene but rather in SCN4A gene that codes for the alpha-subunit of the voltage gated sodium channel. |
The CLCN1 (cholride voltage-gated channel 1) is a critical aspect in the function of skeletal muscle cells. The protein produced from this gene controls the flow of negatively charged chloride ions into these cells for charge equalisation to prevent the abnormal contraction of muscles. This chloride channel is responsible for up to 80% of the resting sarcolemmal conductance.[7,[8],[9]. It is located at 7q34, which is the long arm of chromosome 7 at position 34. A mutation within the CLCN1 gene causes alterations in the structure and function of the chloride channel. This reduces the flow of chloride ions into skeletal muscle cells which induces prolonged muscle contractions.
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