Some early signs of HIBMs includes:

- Difficulty walking on heels, and difficulty running;

- Weak index finger;

- Frequent loss of balance.

- On muscle biopsy, the typical finding includes inclusion bodies, rimmed vacuoles and accumulation of aberrant proteins similar to those found in senile plaques of Alzheimer's disease (amyloid beta, hyperphosphorylated tau, amongst others)

Common symptoms of the disease are weakness and atrophy in the distal muscles of the lower limbs which progresses to the hands and arms, then to the trunk, neck and face. Respiratory impairment often follows.

Hereditary inclusion body myopathies (HIBM) are a heterogeneous group of very rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.

HIBMs are a group of muscle wasting disorders, which are uncommon in the general world population. One autosomal recessive form of HIBM is known as IBM2 or GNE myopathy, which is a common genetic disorder amongst people of Iranian Jewish descent. IBM2 has also been identified in other minorities throughout the world, including people of Asian (Japanese and others), European, and South American origin, as well as Muslim people in the Middle Eastern, Palestinian, and Iranian origin. In Japan and many East Asian countries, this disorder is known as Distal Myopathy with Rimmed Vacuoles (DMRV).

IBM2 causes progressive muscle weakness and wasting. Muscle wasting usually starts around the age of 20 – 30 years, although young onset at 17 and old onset at 52 has been recorded. As such, it affects the most productive times of our lives. It can progress to marked disability within 10 – 15 years, confining many people with IBM2 to a wheelchair. The weakness and severity can vary from person to person. In some, weakness in the legs is noticed first. In few others, the hands are weakened more rapidly than the legs. Weakness is progressive, which means the muscle becomes weaker over time. IBM2 does not seem to affect the brain, internal organs or sensation. The quadriceps are relatively spared, and remain strong until the late stages of disease, which is the reason IBM2 is often referred to as Quadriceps Sparing Myopathy (QSM).

The symptoms of CCD are variable, but usually involve hypotonia (decreased muscle tone) at birth, mild delay in child development (highly variable between cases), weakness of the facial muscles, and skeletal malformations such as scoliosis and hip dislocation.

Symptoms may be present at birth or may appear at any stage of life. There appears to be a growing number of people who do not become symptomatic until adulthood to middle age. While generally not progressive, again there appears to be a growing number of people who do experience a slow clinically significant progression of symptomatology. These cases may hypothetically be due to the large number of gene mutations of ryanodine receptor malfunction, and with continued research may in fact be found to be clinical variants.

The onset of this disease can begin even before birth but is more commonly in childhood or later into adult life. The progression is slow, with symptoms of weakness and walking difficulties sometimes not presenting until middle age. Early symptoms include Gower's sign ("climbing" up the thighs with the hands when rising from the floor) and tiptoe-walking caused by the beginning of contractures.

Bethlem myopathy affects about 1 in 200,000 people. Contractures of the fingers are a typical symptom of Bethlem myopathy but not of the related Ullrich's myopathy (which does include contractures of arms and legs, as does Bethlem myopathy). Serum creatine kinase is elevated in Bethlem myopathy, as there is ongoing muscle cell death. Patients with Bethlem myopathy may expect a normal life span and continued mobility into adulthood. There is currently no cure for this disorder, but the contractures of the legs can be alleviated with heel-cord surgery followed by bracing and regular physical therapy. Repeated surgeries to lengthen the heel cords may be needed as the child grows to adulthood.

Physical expression of nemaline myopathy varies greatly, but weakness is usually concentrated in the proximal muscles, particularly respiratory, bulbar and trunk muscles. People with severe NM show obvious symptoms at birth, while those with intermediate or mild NM may initially appear unaffected. Babies with NM are frequently observed to be "floppy" and hypotonic. Children born with NM often gain strength as they grow, though the effect of muscle weakness on body features may become more evident with time. Adults with NM typically have a very slender physique.

Multicore myopathy, also referred to as minicore myopathy, is associated with small areas of decreased oxidative activities, resulting in areas that appear in this histology as “cores”. These appear through microscopy very similar to central core, however the cores are typically smaller in multicore myopathy. As with congenital fiber type disproportion, patients have a greater number of type 1 fibers. Overall, approximately half of diagnosed individuals report no progression of muscle weakness, while half report a very slow progression.

Bulbar (throat) muscle weakness is a main feature of nemaline myopathy. Most individuals with severe NM are unable to swallow and receive their nutrition through feeding tubes. Most people with intermediate and mild NM take some or all of their nutrition orally. Bulbar muscle impairment may also lead to difficulty with communication. People with NM often have hypernasal speech as a result of poor closure of the velopharyngeal port (between the soft palate and the back of the throat). Communicative skills may be enhanced through speech therapy, oral prosthetic devices, surgery, and augmentative communication devices. Individuals with NM are usually highly sociable and intelligent, with a great desire to communicate.

There are three major types of inheritance for this disease: Autosomal dominant, autosomal recessive and de novo.

- The most severe form is autosomal recessive and it also has the earliest onset. It usually involves all three muscle tissues and leads to cardiac and respiratory failure as well as intestinal obstruction.

- Autosomal Dominant inheritance shows a later onset and slower progression. It usually involves only one or two of the muscle tissues.

- De novo diseases occur when a new mutation arises in the person that was not inherited through either parent. This form has a wide range of symptoms and varies depending on the mutation made.

Congenital fiber type disproportion affects skeletal muscle, typically causing weakness in the shoulders, upper arms, thighs, and hips. Skeletal muscle is made up of two kinds of fiber, type 1 and type 2. In congenital fiber type disproportion, type 1 fibers are not only smaller but often more abundant than type 2 fibers. This leads to affected individuals being able to maintain an active lifestyle, though they usually have lower levels of stamina.

Severity with this disease varies greatly, but people typically present symptoms by the age of one. Individuals do not usually worsen with time, and cases have even been reported of improvements.

Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery.

Symptoms of CNM include severe hypotonia, hypoxia-requiring breathing assistance, and scaphocephaly. Among centronuclear myopathies, the X-linked myotubular myopathy form typically presents at birth, and is thus considered a congenital myopathy. However, some centronuclear myopathies may present later in life.

Central core disease (CCD), also known as central core myopathy, is an autosomal dominant congenital myopathy (inborn muscle disorder). It was first described by Shy and Magee in 1956. It is characterized by the appearance of the myofibril under the microscope.

In terms of the signs (and symptoms) of oculopharyngeal muscular dystrophy would be consistent with the following:

Though the aforementioned signs/symptoms are the most common, there have been cases though rare, where the peripheral nervous system has had involvement with significant reduction of myelinated fibers

In homozygous cases, this muscular dystrophy is severe and starts earlier in the affected individuals life.

Common symptoms include muscle weakness, cramps, stiffness, and tetany.

Bethlem myopathy is an autosomal dominant myopathy, classified as a congenital form of muscular dystrophy, that is caused by a mutation in one of the three genes coding for type VI collagen. These include COL6A1, COL6A2, and COL6A3.

As with other myopathies, the clinical manifestations of MTM/CNM are most notably muscle weakness and associated disabilities. Congenital forms often present with neonatal low muscle tone, severe weakness, delayed developmental milestones (particularly gross motor milestones such as head control, crawling, and walking) and pulmonary complications (presumably due to weakness of the muscles responsible for respiration). While some patients with centronuclear myopathies remain ambulatory throughout their adult life, others may never crawl or walk and may require wheelchair use for mobility. There is substantial variability in the degree of functional impairment among the various centronuclear myopathies. Although this condition only affects the voluntary muscles, several children have suffered from cardiac arrest, possibly due to the additional stress placed on the heart.

Other observed features have been high arched palate, long digits, bell shaped chest and long face.

Myotubular myopathy only affects muscles and does not impact intelligence in any shape or form.

X-linked myotubular myopathy was traditionally a fatal condition of infancy, with life expectancy of usually less than two years. There appears to be substantial variability in the clinical severity for different genetic abnormalities at that same MTM1 gene. Further, published cases show significant differences in clinical severity among relatives with the same genetic abnormality at the MTM1 gene. Most truncating mutations of MTM1 cause a severe and early lethal phenotype, while some missense mutations are associated with milder forms and prolonged survival (up to 54 years).

Centronuclear myopathies typically have a milder presentation and a better prognosis. Recently, researchers discovered mutations at the gene dynamin 2 (DNM2 on chromosome 19, at site 19p13.2), responsible for the autosomal dominant form of centronuclear myopathy. This condition is now known as dynamin 2 centronuclear myopathy (abbreviated DNM2-CNM). Research has indicated that patients with DNM2-CNM have a slowly progressive muscular weakness usually beginning in adolescence or early adulthood, with an age range of 12 to 74 years.

Individuals with KSS present initially in a similar way to those with typical CPEO. Onset is in the first and second decades of life.

The first symptom of this disease is a unilateral ptosis, or difficulty opening the eyelids, that gradually progresses to a bilateral ptosis. As the ptosis worsens, the individual commonly extends their neck, elevating their chin in an attempt to prevent the eyelids from occluding the visual axis. Along with the insidious development of ptosis, eye movements eventually become limited causing a person to rely more on turning the head side to side or up and down to view objects in the peripheral visual field.

At DeathMlg

None as systemic causes; mainly hereditary

Onset in childhood

Inflammatory myopathies – dermatomyositis, polymyositis (rarely)

Infectious myopathies

Endocrine and metabolic disorders – hypokalemia, hypocalcemia, hypercalcemia

Onset in adulthood

Inflammatory myopathies – polymyositis, dermatomyositis, inclusion body myositis, viral (HIV)

Infectious myopathies

Endocrine myopathies – thyroid, parathyroid, adrenal, pituitary disorders

Toxic myopathies – alcohol, corticosteroids, narcotics, colchicines, chloroquine

Critical illness myopathy

Metabolic myopathies

Paraneoplastic myopathy

Symptoms typically begin in childhood and are progressive, often resulting in death by early adulthood. Symptoms of PKAN begin before middle childhood, and most often are noticed before ten years of age. Symptoms include:

- dystonia (repetitive uncontrollable muscle contractions that may cause jerking or twisting of certain muscle groups)

- dysphagia & dysarthria due to muscle groups involved in speech being involved

- rigidity/stiffness of limbs

- tremor

- writhing movements

- dementia

- spasticity

- weakness

- seizures (rare)

- toe walking

- retinitis pigmentosa, another degenerative disease that affects the individual’s retina, often causing alteration of retinal color and progressive deterioration of the retina at first causing night blindness and later resulting in a complete loss of vision.

25% of individuals experience an uncharacteristic form of PKAN that develops post-10 years of age and follows a slower, more gradual pace of deterioration than those pre-10 years of age. These individuals face significant speech deficits as well as psychiatric and behavioral disturbances.

Being a progressive, degenerative nerve illness, PKAN leads to early immobility and often death by early adulthood. Death occurs prematurely due to infections such as pneumonia, and the disease in itself is technically not life limiting.

KSS results in a pigmentation of the retina, primarily in the posterior fundus. The appearance is described as a "salt-and-pepper" appearance. There is diffuse depigmentation of the retinal pigment epithelium with the greatest effect occurring at the macula. This is in contrast to retinitis pigmentosa where the pigmentation is peripheral. The appearance of the retina in KSS is similar to that seen in myotonic dystrophy type 1 (abbreviated DM1). Modest night-blindness can be seen in patients with KSS. Visual acuity loss is usually mild and only occurs in 40–50% of patients.

Limb girdle syndrome is a term to describe several distinct medical conditions including polymyositis, myopathy associated with endocrine disease, metabolic myopathy, drug-induced myopathy and limb-girdle muscular dystrophy.

Limb girdle syndrome is weakness located and concentrated around the proximal limb muscles. There are many causes, manifestations and treatments.

Distal muscular dystrophy (or distal myopathy) is a group of disorders characterized by onset in the hands or feet. Many types involve dysferlin, but it has been suggested that not all cases do.

Types include:

DYSF is also associated with limb-girdle muscular dystrophy type 2B.

Distal muscular dystrophy is a type of muscular dystrophy that affects the muscles of the extremities, the hands, feet, lower arms, or lower legs. The cause of this dystrophy is very hard to determine because it can be a mutation in any of at least eight genes and not all are known yet. These mutations can be inherited from one parent, autosomal dominant, or from both parents, autosomal recessive. Along with being able to inherit the mutated gene, distal muscular dystrophy has slow progress therefore the patient may not know that they have it until they are in their late 40’s or 50’s. There are eight known types of distal muscular dystrophy. They are Welander’s distal myopathy, Finnish (tibial) distal myopathy, Miyoshi distal myopathy, Nonaka distal myopathy, Gowers–Laing distal myopathy, hereditary inclusion-body myositis type 1, distal myopathy with vocal cord and pharyngeal weakness, and ZASP-related myopathy. All of these affect different regions of the extremities and can show up as early as 5 years of age to as late as 50 years old. Doctors are still trying to determine what causes these mutations along with effective treatments.

Symptoms typically are onset in the adult years, although, childhood cases have also been observed. Common symptoms include a loss of coordination which is often seen in walking, and slurred speech. ADCA primarily affects the cerebellum, as well as, the spinal cord. Some signs and symptoms are:

The prolonged muscle contractions, which occur most commonly in the leg muscles in recessive mutations, and more commonly in the hands, face, and eyelids in dominant mutations, are often enhanced by inactivity, and in some forms are relieved by repetitive movement known as "the warm-up effect". This effect often diminishes quickly with rest. Some individuals with myotonia congenita are prone to falling as a result of hasty movements or an inability to stabilize themselves after a loss of balance. During a fall, a person with myotonia congenita may experience partial or complete rigid paralysis that will quickly resolve once the event is over. 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.

The two major types of myotonia congenita are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease, and causes more severe myotonia, muscle stiffness and transient weakness. Although myotonia in itself is not normally associated with pain, cramps or myalgia may develop. 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. This muscle weakness is not observed in people with Thomsen disease. However, in recent times, as more of the individual mutations that cause myotonia congenita are identified, these limited disease classifications are becoming less widely used.

Early symptoms in a child may include:

- Difficulty swallowing

- Gagging

- Stiff movements that improve when they are repeated

- Frequent falling

- Difficulties opening eyelids after strenuous contraction or crying (von Graefe's sign)

Possible complications may include:

- Aspiration pneumonia (caused by swallowing difficulties)

- Frequent choking or gagging in infants (also caused by swallowing difficulties)

- Abdominal muscle weakness

- Chronic joint problems

- Injury due to falls

Patients with CED complain of chronic bone pain in the legs or arms, muscle weakness (myopathy) and experience a waddling gait. Other clinical problems associated with the disease include increased fatigue, weakness, muscle spasms, headache, difficulty gaining weight, and delay in puberty. Some patients have an abnormal or absent tibia, may present with a flat foot, or scoliosis.

This disease may also cause bones to become abnormally hardened which is referred to as sclerosis. This hardening may affect the bones at the base of the skull or those in the hands, feet, or jaw. This causes ongoing pain and aching within the body parts that are affected. The pain has been described as either a hot electric stabbing pain, an ever-increasing pressure sensation around the bones (especially before electrical storms) or as a constant ache that radiates through several long bones at once. Pain may also occur in the hips, wrists, knees and other joints as they essentially just 'lock-up' (often becoming very stiff, immobile and sore), mostly when walking up or down staircases, writing for extended periods of time, or during the colder months of the year. Those with the disease tend to have a very characteristic walk medically diagnosed as a 'waddling gait'. This is observed by the broad-based gait with a duck-like waddle to the swing phase, the pelvis drops to the side of the leg being raised, notable forward curvature of the lumbar spine and a marked body swing.

The pain is especially severe during a 'flare-up', these can be unpredictable, exhausting and last anywhere from a few hours to several weeks. This is a common occurrence for several CED patients, often causing myopathy and extensive sleep deprivation from the chronic, severe and disabling pain. Patients may even require the use of a wheelchair (or additional carer's help with getting dressed, showering, mobility/shopping, preparing meals or lifting heavy items) especially when bedridden or housebound for days or weeks at a time. 'Flare-ups' may be attributed to, or exacerbated by growth spurts, stress, exhaustion, exercise, standing or walking for too long, illness, infection, being accidentally knocked/hurt or injured, after surgery/anaesthetics, cold weather, electrical storms, and sudden changes in barometric pressure.

CED may also affect internal organs, the liver and spleen, which may become enlarged. A loss of vision and/or hearing can occur if bones are adversely affected by the hardening in the skull. Hence proactive specialist check-ups, X-rays, diagnostic tests/scans, and regular blood tests are recommended on an annual basis to monitor the CED bony growth and secondary medical issues that may arise from this condition.