The exact mechanisms of these diseases are not well understood. GNE/MNK a key enzyme in the sialic acid biosynthetic pathway, and loss-of-function mutations in GNE/MNK may lead to a lack of sialic acid, which in turn could affect sialoglycoproteins. GNE knockout mice show problems similar to people with IBM and in people with IBM dystroglycan has been found to lack sialic acid. However, the part of the dystroglycan that is important in muscle function does not seem to be affected. Another protein, neural cell adhesion molecule is under-sialyated in people with IBM, but as of 2016 it had no known role in muscle function.

The different forms have different mutations and inheritance patterns. See the detailed OMIM descriptions for details (given above).

Inclusion body myositis (IBM) is an inflammatory muscle disease characterized by slowly progressive weakness and wasting of both distal and proximal muscles, most apparent in the muscles of the arms and legs. There are two types: sporadic inclusion body myositis (sIBM), which is more common, and hereditary inclusion body myopathy (hIBM).

In sporadic inclusion body myositis [MY-oh-sigh-tis], two processes, one autoimmune and the other degenerative, appear to occur in the muscle cells in parallel. The inflammation aspect is characterized by the cloning of T cells that appear to be driven by specific antigens to invade muscle fibers. The degeneration aspect is characterized by the appearance of holes in the muscle cell vacuoles, deposits of abnormal proteins within the cells and in filamentous inclusions (hence the name inclusion body myositis).

Weakness comes on slowly (over months or years) and progresses steadily and usually leads to severe weakness and wasting of arm and leg muscles. It is more common in men than women. Patients may become unable to perform activities of daily living and most require assistive devices within 5 to 10 years of symptom onset. sIBM is not considered a disorder, but the risk of serious injury due to falls is increased. One common and potentially fatal complication is dysphagia. There is no effective treatment for the disease.

sIBM is a rare yet increasingly prevalent disease and is the most common cause of inflammatory myopathy in people over age 50. Recent research from Australia indicates that the incidence of IBM varies in different populations and ethnic groups. The authors found that the current prevalence was 14.9 per million in the overall population, with a prevalence of 51.3 per million population in people over 50 years of age. As seen in these numbers, sIBM is an age-related disease – its incidence increases with age and symptoms usually begin after 50 years of age. It is the most common acquired muscle disorder seen in people over 50, although about 20% of cases display symptoms before the age of 50.

The Roussy–Lévy syndrome is not a fatal disease and life expectancy is normal. However, due to progressive muscle wasting patients may need supportive orthopaedic equipment or wheelchair assistance.

A 2006 study followed 223 patients for a number of years. Of these, 15 died, with a median age of 65 years. The authors tentatively concluded that this is in line with a previously reported estimate of a shortened life expectancy of 10-15 years (12 in their data).

The cause of IBM is unknown. IBM likely results from the interaction of a number of genetic and environmental factors.

There are two major theories about how sIBM is caused. One hypothesis suggests that the inflammation-immune reaction, caused by an unknown trigger – likely an undiscovered virus or an autoimmune disorder– is the primary cause of sIBM and that the degeneration of muscle fibers and protein abnormalities are secondary features. Despite the arguments "in favor of an adaptive immune response in sIBM, a purely autoimmune hypothesis for sIBM is untenable because of the disease's resistance to most immunotherapy."

The second school of thought advocates the theory that sIBM is a degenerative disorder related to aging of the muscle fibers and that abnormal, potentially pathogenic protein accumulations in myofibrils play a key causative role in sIBM (apparently before the immune system comes into play). This hypothesis emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, proteosome inhibition, and endoplasmic reticulum (ER) stress.

One review discusses the "limitations in the beta-amyloid-mediated theory of IBM myofiber injury."

Dalakas (2006) suggested that a chain of events causes IBM—some sort of virus, likely a retrovirus, triggers the cloning of T cells. These T cells appear to be driven by specific antigens to invade muscle fibers. In people with sIBM, the muscle cells display “flags” telling the immune system that they are infected or damaged (the muscles ubiquitously express MHC class I antigens) and this immune process leads to the death of muscle cells. The chronic stimulation of these antigens also causes stress inside the muscle cell in the endoplasmic reticulum (ER) and this ER stress may be enough to cause a self-sustaining T cell response (even after a virus has dissipated). In addition, this ER stress may cause the misfolding of protein. The ER is in charge of processing and folding molecules carrying antigens. In IBM, muscle fibers are overloaded with these major histocompatibility complex (MHC) molecules that carry the antigen protein pieces, leading to more ER stress and more protein misfolding.

A self-sustaining T cell response would make sIBM a type of autoimmune disorder. When studied carefully, it has not been impossible to detect an ongoing viral infection in the muscles. One theory is that a chronic viral infection might be the initial triggering factor setting IBM in motion. There have been a handful of IBM cases—approximately 15—that have shown clear evidence of a virus called HTLV-1. The HTLV-1 virus can cause leukemia, but in most cases lies dormant and most people end up being lifelong carriers of the virus. One review says that the best evidence points towards a connection with some type of retrovirus and that a retroviral infection combined with immune recognition of the retrovirus is enough to trigger the inflammation process.

- amyloid protein

- The hypothesis that beta amyloid protein is key to IBM has been supported in a mouse model using an Aβ vaccine that was found to be effective against inclusion body myositis in mouse models. Although this vaccine is likely not safe for human use, it still shows that attacking Aβ has efficacy in mice against IBM.

- Following up on earlier leads, the Greenberg group report finding that the protein TDP-43 is a very prominent and highly sensitive and specific feature of IBM. This protein is normally found within the nucleus but in IBM is found in the cytoplasm of the cell. This important advance should help develop a new screening technique for IBM and may provide clues in terms of a therapeutic approach

New research resources have become available for the NM community, such as the CMDIR (registry) and the CMD-TR (biorepository). These two resources connect families and individuals interested in participating in research with the scientists that aim to treat or cure NM. Some research on NM seeks to better understand the molecular effects the gene mutations have on muscle cells and the rest of the body and to observe any connections NM may have to other diseases and health complications.

Muscular atrophy decreases qualities of life as the sufferer becomes unable to perform certain tasks or worsen the risks of accidents while performing those (like walking). Muscular atrophy increases the risks of falling in conditions such as inclusion body myositis (IBM) . Muscular atrophy affects a high number of the elderly.

There are many diseases and conditions which cause a decrease in muscle mass, known as atrophy, including activity, as seen when a cast is put on a limb, or upon extended bedrest (which can occur during a prolonged illness); cachexia - which is a syndrome that is a co-morbidity of cancer and congestive heart failure; chronic obstructive pulmonary disease; burns, liver failure, etc., and the wasting Dejerine-Sottas syndrome (HMSN Type III). Glucocorticoids, a class of medications used to treat allergic and other inflammatory conditions can induce muscle atrophy by increasing break-down of muscle proteins. Other syndromes or conditions which can induce skeletal muscle atrophy are liver disease, and starvation.

Some horse organizations have instituted rules to attempt to eliminate this widespread disease. The American Quarter Horse Association (AQHA) mandates testing for foals descended from Impressive if both of the foal's parents were not homozygous negative (N/N) for the gene, and, since 2007, has not registered foals homozygous (H/H) for the gene. Since 2007, the Appaloosa Horse Club (ApHC) has required foals descended from Impressive to be tested, so that the results may be recorded on its certificate. The American Paint Horse Association (APHA) mandated that, after 2017, stallions must be tested for HYPP so that mare owners may make an informed decision before choosing a stallion for breeding to their mare.

dHMN V has a pattern of autosomal dominance, meaning that only one copy of the gene is needed for the development of the disease. However, there is incomplete penetrance of this disorder, meaning that some individuals with the disease-causing mutations will not display any symptoms. Mutations on chromosome 7 have been linked to this disease. It is allelic (i.e., caused by mutations on the same gene) with Charcot–Marie–Tooth disease and with Silver’s Syndrome, a disorder also characterized by small muscle atrophy in the hands.

Another rare form of dHMN V is associated with a splicing mutation in REEP-1, a gene often associated with hereditary spastic neuroplegia.

Distal hereditary motor neuropathy type V (dHMN V) is a particular type of neuropathic disorder. In general, distal hereditary motor neuropathies affect the axons of distal motor neurons and are characterized by progressive weakness and atrophy of muscles of the extremities. It is common for them to be called "spinal forms of Charcot-Marie-Tooth disease (CMT)", because the diseases are closely related in symptoms and genetic cause. The diagnostic difference in these diseases is the presence of sensory loss in the extremities. There are seven classifications of dHMNs, each defined by patterns of inheritance, age of onset, severity, and muscle groups involved. Type V (sometimes notated as Type 5) is a disorder characterized by autosomal dominance, weakness of the upper limbs that is progressive and symmetrical, and atrophy of the small muscles of the hands.

In northern Scandinavia, the prevalence of myotonia congenita has been estimated at 1:10,000.

Myotonia congenita is estimated to affect 1 in 1,000,000 people worldwide.

Both Thomsen and Becker myotonia have high phenotype variability. Severity of symptoms can vary greatly between individuals and throughout the lives of the individuals themselves. This may be partly because there are over 130 currently known different mutations that can cause the disorder, each with their own specifics, and also because myotonia congenita is an ion channel disorder, and ion channels are sensitive to internal and external environmental factors. It has been shown that pregnancy and the use of diuretics aggravate myotonia, and both these conditions are linked to the loss of divalent cations such as magnesium and calcium. It has further been shown that in pharmacological induced myotonia in isolated rat muscle, myotonia could be dampened by increasing the magnesium and calcium content of the extracellular medium. This has also been shown for isolated human muscle.

Adrenaline/epinephrine is well known to make myotonia worse in most individuals with the disorder, and a person with myotonia congenita may experience a sudden increase in difficulty with mobility in a particularly stressful situation during which adrenaline is released.

Due to the invisible nature of the disorder, the fact that those with myotonia congenita often appear very fit and able bodied, the general lack of knowledge about the disorder by the general and medical community, and often by the individual themselves, and the potential for inconsistency with the symptoms, many people with myotonia congenita have experienced a degree of social persecution at one time or another because of the effects of their disorder.

Paramyotonia congenita is considered an extremely rare disorder, though little epidemiological work has been done. Prevalence is generally higher in European-derived populations and lower among Asians. Epidemiological estimates have been provided for the German population. There, it was estimated that the prevalence of PC is between 1:350,000 (0.00028%) and 1:180,000 (0.00056%). However, the German population of patients with PC is not uniformly distributed across the country. Many individuals with PC herald from the Ravensberg area in North-West Germany, where a founder effect seems to be responsible for most cases. The prevalence here is estimated at 1:6000 or 0.017%.

Roussy–Lévy syndrome, also known as Roussy–Lévy hereditary areflexic dystasia, is a rare genetic disorder of humans that results in progressive muscle wasting. It is caused by mutations in the genes that code for proteins necessary for the functioning of the myelin sheath of the neurons, affecting the conductance of nerve signals and resulting in loss of muscles' ability to move.

The condition affects people from infants through adults and is inherited in an autosomal dominant manner. Currently, no cure is known for the disorder.

X-linked myopathy with excessive autophagy (XMEA) is a rare childhood onset disease characterized by slow progressive vacuolation and atrophy of skeletal muscle. There is no known cardiac or intellectual involvement.

Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. Some cases are seriously disabling while others are less disabling and are compatible with a productive and full life. The majority of individuals with HSP have a normal life expectancy.

In 1994, researchers at the University of Pittsburgh, with a grant from horse organizations, isolated the genetic mutation responsible for the problem and developed a blood test for it. Using this test, horses may be identified as:

- H/H, meaning they have the mutation and it is homozygous. These horses always pass on the disease.

- N/H, meaning they have the mutation and it is heterozygous. These horses are affected to a lesser degree and pass on the disease 50% of the time.

- N/N, meaning they do not have the mutation and cannot pass it on, even if they are descendants of Impressive.

In the case of the horse Impressive, the muscles were always contracting which was equivalent to a constant work-out. Thus the development of an "impressive" musculature.

Nemaline myopathy (also cake called rod myopathy or nemaline rod myopathy) is a congenital, hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout one's life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy.

"Myopathy" means muscle disease. Muscle fibers from a person with nemaline myopathy contains thread-like rods, sometimes called nemaline bodies. While the rods are diagnostic of the disorder, they are more likely a byproduct of the disease process rather than causing any dysfunction on their own. People with nemaline myopathy (NM) usually experience delayed motor development, or no motor development in severe cases, and weakness may occur in all of the skeletal muscles, such as muscles in the arms, legs, torso, neck flexors, throat, and face. The weakness tends to be more severe in the proximal muscles rather than the distal muscles. The ocular muscles are normally spared.

The disorder is often clinically categorized into groups with wide ranges of overlapping severity, from the most severe neonatal form which is incompatible with life, to a form so mild that it may not be diagnosed since the person appears to function at the lowest end of normal strength and breathing adequacy. Sporadic late onset nemaline myopathy (SLONM) is not a congenital disorder and is considered a different muscle disease from NM, which has its onset at birth or early childhood. Respiratory problems are usually a primary concern for people with all forms of NM, and respiratory infections are quite common. NM shortens life expectancy, particularly in the more severe forms, but aggressive and proactive care allows most individuals to survive and even lead active lives.

Nemaline myopathy is one of the neuromuscular diseases covered by the Muscular Dystrophy Association in the United States.

Central core disease is inherited in an autosomal dominant fashion. Most cases have demonstrable mutations in the ryanodine receptor type 1 ("RYR1") gene, which are often "de novo" (newly developed). People with CCD are at risk for malignant hyperthermia (MH) when receiving general anesthesia.

There is no specific treatment but triggering anesthetics are avoided and relatives are screened for "RYR1" mutations as these may make them susceptible to MH.

HSP is a group of genetic disorders. It follows general inheritance rules and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. Over 70 genotypes had been described, and over 50 genetic loci have been linked to this condition. Ten genes have been identified with autosomal dominant inheritance. One of these SPG4 accounts for ~50% of all genetically solved cases cases, or approximately 25% of all HSP cases. Twelve genes are known to be inherited in an autosomal recessive fashion. Collectively this latter group account for ~1/3 cases.

Most altered genes have known function, but for some the function haven’t been identified yet. All of them are listed in the gene list below, including their mode of inheritance. Some examples are spastin (SPG4) and paraplegin (SPG7) are both AAA ATPases.

Facioscapulohumeral muscular dystrophy (FSHMD, FSHD or FSH)—originally named Landouzy-Dejerine—is a usually autosomal dominant inherited form of muscular dystrophy (MD) that initially affects the skeletal muscles of the face (facio), scapula (scapulo) and upper arms (humeral). FSHD is the third most common genetic disease of skeletal muscle. Orpha.net lists the prevalence as 4/100,000 while a 2014 population-based study in the Netherlands reported a significantly higher prevalence of 12 in 100,000.

Symptoms may develop in early childhood and are usually noticeable in the teenage years, with 95% of affected individuals manifesting disease by age 20 years. A progressive skeletal muscle weakness usually develops in other areas of the body as well; often the weakness is asymmetrical. Life expectancy can be threatened by respiratory insufficiency, and up to 20% of affected individuals become severely disabled, requiring use of a wheel chair or mobility scooter. In a Dutch study, approximately 1% of patients required (nocturnal or diurnal) ventilatory support. Non-muscular symptoms frequently associated with FSHD include subclinical sensorineural hearing loss and retinal telangiectasia.

In more than 95% of known cases, the disease is associated with contraction of the D4Z4 repeat in the 4q35 subtelomeric region of Chromosome 4. Seminal research published in August 2010 now shows the disease requires a second mechanism, which for the first time provides a unifying theory for its underlying genetics. The second mechanism is a "toxic gain of function" of the DUX4 gene, which is the first time in genetic research that a "dead gene" has been found to "wake up" and cause disease.

Building on the 2010 unified theory of FSHD, researchers in 2014 published the first proposed pathophysiology definition of the disease and four viable therapeutic targets for possible intervention points.

Myotubular myopathy, also known as centeronuclear myopathy, is recognized by pain during exercise and difficulty walking. People affected by this disease typically are wheel-chair-bound by middle adulthood, have weakness in the muscles involved in eye movement, nerve function disorders, and some form of intellectual disability. Myotubular myopathy is very rare, with less than 50 families currently affected.

Genetically, myotubular myopathy can have two causes: autosomal dominant and autosomal recessive. When caused by a mutation in the DNM2 gene, the disorder is autosomal dominant, meaning it can be passed on by one mutated gene. When the mutation takes place in the BIN1 gene, the disease is instead autosomal recessive, and both genes must be mutated for the disease to be inherited. Autosomal recessive onset is most common.