The cardinal feature of MC is delayed relaxation of contracted skeletal muscle. It is acknowledged that there is significant variability in the phenotype of both autosomal and recessively inherited MC; this can hinder prompt diagnosis and management. Identical mutations can result in significantly different clinical presentations, and the relationship between genotype and phenotype in these channelopathies is considered to be extremely complex.[13] Conversely, some specific mutations appear to produce a highly reproducible phenotype. Detailed family history is often helpful in elucidating an autosomal or recessive inheritance pattern though this may be absent in sporadic mutations.

In early childhood, symptoms may include feeding difficulties, including dysphagia, reflux, gagging, and choking. 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. These signs may be subtle; therefore, careful history from patients and their caregivers, as well as clinical examination, is essential. Symptoms often progress initially after they first appear and then plateau.[14]

Muscle stiffness observed in MC is often ameliorated by exercise or repetitive movement. This effect is called the “warm-up” phenomenon (though it is quickly lost on cessation of activity). Men appear to be more severely affected by MC than women. In addition, symptoms often worsen during pregnancy and menstruation; these observations imply that sex hormones affect CIC-1 channel function.[15][16] 

MC is classically defined into distinct clinical diseases based on the mode of inheritance. There are subtle differences between the two diseases. Given the phenotypic variability discussed above, the ultimate diagnosis is achieved with genetic testing.

Becker disease (BD): This is autosomally recessive inherited MC. It is associated with moderate to severe myotonia and transient weakness, though in some cases, this may become progressive. BD generally presents later in childhood than Thomsen disease (TD).[17] Muscle hypertrophy is more prominent in BD than TD and may be particularly visible in the larger muscle groups in the lower limbs.

Thomsen disease (TD): Dominantly inherited MC is associated with an earlier onset of symptoms though these are milder than BD. The mild, progressive, permanent weakness described in BD is not associated with TD.[18] The autosomal dominant mutations causative of TD are associated with reduced penetrance, and identical mutations inherited through generations can cause markedly different phenotypes.

Clinical examination: Myotonia can be observed by asking patients to repeatedly open and close their eyes or to open and close their fist. Repeated tapping of a muscle similarly induces myotonia.[19] Patients may struggle to immediately extend fingers following a handshake. The "warm-up effect" may also be demonstrable.

Biochemical investigations are usually unremarkable, although mild elevations of creatinine kinase have been described up to three to four times the upper limit of normal.[19] Electromyography is a useful tool in the diagnosis of MC however, it is time-consuming, uncomfortable, and results in an overlap between the different channelopathies.[20] It may demonstrate a shower of spontaneous electrical activity in diffuse myotonic discharges or "bursts." There is no electromyographical difference between the two types of MC. Given the widespread availability of genetic testing, muscle biopsy is now rarely performed, but it may show heterogeneous muscle fibers with increased numbers of nuclei and absent type 2B fibers.[19] A muscle biopsy is not necessary to establish a diagnosis of MC.

Genetic testing is considered the gold standard. However, in many patients, mutations within the CLCN1 gene are not identified despite significant clinical features correlating with a myotonic picture. A multigene panel is usually performed initially, including the CLCN1 gene, as well as other genes of interest such as SCN4A (discussed in differential diagnoses). Genetic testing and selection of techniques used should be undertaken by specialized centers in order to evaluate variants of unknown significance (VUS), correlate identified mutations with clinical phenotype, and minimize costs. If a multigene panel does not identify an explanatory mutation, genomic techniques, including exome sequencing and mitochondrial sequencing, may be employed.

Pharmacological management of MC is not always indicated, and patients should be evaluated by a neurologist to assess the requirement for medication prior to its initiation.[21] Lifestyle modifications include avoidance of identified triggers such as stress and cold. Exercise, particularly gymnastics, is anecdotally reported to be beneficial in relieving myotonia; however, the effect needs to be further investigated. 

Medications that are used generally aim to reduce hypersensitivity of the muscle membrane by blocking sodium ion flow.[22] Mexiletine is the most commonly prescribed medication but requires ECG monitoring of the QT interval prior to and during use.[23] It is classified as a class 1b antiarrhythmic and is a derivative of the local anesthetic lidocaine. Mexiletine is primarily used in the management of ventricular arrhythmias by blocking the rapid influx of sodium responsible for phase 0 of the action potential (AP), shortening the AP, and prolonging the refractory period.[24] 

Side effects may include tremor, dizziness, ataxia, and gastrointestinal disturbance. These adverse effects are usually dose-dependent and reversible on cessation of medication or dose decrement. Phenytoin and other anticonvulsants are also commonly used.[25] 

Potassium channels are a novel target. The potassium channel activator retigabine has been investigated in murine MC models and demonstrated to significantly improve the severity of myotonia in vivo.[22] However, it is recognized that there remains a paucity of evidence guiding the pharmacological management of MC.[26]

MC is the most common non-dystrophic myotonia (NDM). The condition is non-dystrophic because the muscle tissue is not structurally compromised as part of the disease process, and instead, myotonia is caused by defective ion channels in skeletal muscle resulting in discord within ion conductance. In addition to dysfunctional anion channels seen in MC, mutations within cation channels, namely sodium ion channels, cause paramyotonia congenita (PMC), potassium-aggravated myotonia (PAM), and potassium-sensitive (hyperkalemic) periodic paralysis (HyperPP).[3] 

It is mutations in the SCN4A gene that result in loss of function of these voltage-gated sodium channels. Symptoms are usually worse in the lower limbs in MC (patients often struggle to stand up quickly) whereas, in PAM, the eyes and face are more severely affected. Myotonia associated with HyperPP is mild and particularly associated with eyelids and tongue.[19] 

Distinguishing MC from other disorders is often possible clinically with careful consideration of exacerbating or alleviating factors, presence of extra-muscular disease, and findings on electromyography. The symptoms and features of potassium channel disorders are worsened following the ingestion of potassium-rich foods, and patients may describe their myotonia as painful. This history is not typical of MC. The myotonic dystrophies are also an important differential to consider when investigating muscle weakness and spasticity in early childhood and infancy. Myotonic dystrophy (MD) type I and II are associated with systemic features, including endocrine dysfunction, cardiac conduction defects, and cataract formation. Additionally, the pattern of muscular weakness observed in MD is very different from that observed in MC.

Neither autosomal nor recessively inherited MC are associated with systemic effects and do not limit life expectancy.[21] This prognosis differs significantly from the disease course of myotonic dystrophy therefore, accurate diagnosis is essential. Once symptoms of MC have appeared, this group of diseases do not typically progress. Becker disease is typically considered to be associated with worse symptoms than those seen in Thomsen disease, and permanent weakness may persist over time. Patients with MC must have access to genetic counseling services in order to make informed decisions regarding family planning.

Care must be taken during anesthesia, particularly with depolarizing muscle relaxants, which are associated with adverse events in MC patients such a profound muscle spasm and difficulties in secondary ventilation.[27] Medications that should be avoided or at least used in caution in patients with MC include:

1. Suxamethonium- may produce a profound muscle spasm and ventilation difficulties.
2. Adrenaline and beta-agonists-can cause aggravation of symptoms
3. Beta antagonist-can potentially increase the severity of symptoms.
4. Colchicine- can trigger myopathy, especially in individuals with renal insufficiency.

Pregnancy has been associated with the worsening of MC; therefore, an interprofessional team is essential throughout gestation, birth, and the postpartum period.

Education and support of patients with MC and their families are essential. The physical appearance of myotonia and its effects can be severely debilitating with a profound psychological impact on affected patients.[20] Conversely, due to muscle hypertrophy associated with MC, patients report that they are victimized and discriminated against as they appear able-bodied. Patients may try to "fight" against the myotonia, which can worsen the effect, and stress is a known exacerbator of symptoms. Therefore, coping strategies to enhance functionality with careful attention to psychological health are vital. Adjustments may be required to the home, school, and work environments to diminish the risk of falls and lessen their impact when they occur. Dietary modifications may be required to enhance safe swallowing and decrease the likelihood of aspiration.

MC is a highly variable but potentially devastating condition affecting patients and their families from early childhood throughout their lives. As this is a genetic condition, there is an important role for genetic testing and counseling in order to test other family members and advise family planning. Effective and safe care of MC, therefore, requires coordination of several medical specialties, including pediatrics and clinical genetics, as well as input from physiotherapists, dieticians, occupational therapists, and psychologists. The role of this interprofessional team is now well-established in specialized centers.