Patients usually begin to notice symptoms in their 50s and the course is usually slowly progressive. Common features include peripheral neuropathy, cardiomyopathy, and hemolytic anemia. Other features include limb chorea, facial tics, other oral movements (lip and tongue biting), seizures, a late-onset dementia, and behavioral changes.

Endocardial fibroelastosis (EFE) is a rare heart disorder usually occurring in children two years old and younger. It may also be considered a reaction to stress, not necessarily a specific disease.

It should not be confused with endomyocardial fibrosis.

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.

The incidence of this disease is not precisely known but it is considered to be rare (< 1/10 population). It has been reported in 15 families to date mostly from Canada, Finland and France.

This disease usually presents between the ages of 5 to 10 years old. The usual picture is with weakness involving the upper legs and affects activities such as running and climbing stairs. As the condition progresses, patients tend to experience weakness in their lower legs and arms. Some remain able to walk in advanced age, while others require assistance in adulthood.

Like other mitochrondrial diseases, "MNGIE is a multisystem disorder". MNGIE primarily affects the gastrointestinal and neurological systems. Gastrointestinal symptoms may include gastrointestinal dysmotility, due to inefficient peristalsis, which may result in pseudo-obstruction and cause malabsorption of nutrients. Additionally, gastrointestinal symptoms such as borborygmi, early satiety, diarrhea, constipation, gastroparesis, nausea, vomiting, weight loss, and diverticulitis may be present in MNGIE patients. Neurological symptoms may include diffuse leukoencephalopathy, peripheral neuropathy, and myopathy. Ocular symptoms may include retinal degeneration, ophthalmoplegia, and ptosis. Those with MNGIE are often thin and experience continuous weight loss. The characteristic thinness of MNGIE patients is caused by multiple factors including inadequate caloric intake due to gastrointestinal symptoms and discomfort, malabsorption of food from bacterial overgrowth due to decreased motility, as well as an increased metabolic demand due to inefficient production of ATP by the mitochondria.

EFE is characterized by a thickening of the innermost lining of the heart chambers (the endocardium) due to an increase in the amount of supporting connective tissue and elastic fibres. It is an uncommon cause of unexplained heart failure in infants and children, and is one component of HEC syndrome. Fibroelastosis is strongly seen as a primary cause of restrictive cardiomyopathy in children, along with cardiac amyloidosis, which is more commonly seen in progressive multiple myeloma patients and the elderly.

Subjects' symptoms from non-compaction cardiomyopathy range widely. It is possible to be diagnosed with the condition, yet not to have any of the symptoms associated with heart disease. Likewise it possible to have severe heart failure, which even though the condition is present from birth, may only manifest itself later in life. Differences in symptoms between adults and children are also prevalent with adults more likely to have heart failure and children from depression of systolic function.

Common symptoms associated with a reduced pumping performance of the heart include:

- Breathlessness

- Fatigue

- Swelling of the ankles

- Limited physical capacity and exercise intolerance

Two conditions though that are more prevalent in noncompaction cardiomyopathy are: tachyarrhythmia which can lead to sudden cardiac death and clotting of the blood in the heart.

This form differs from the infantile principally in the relative lack of cardiac involvement. The onset is more insidious and has a slower progression. Cardiac involvement may occur but is milder than in the infantile form. Skeletal involvement is more prominent with a predilection for the lower limbs.

Late onset features include impaired cough, recurrent chest infections, hypotonia, progressive muscle weakness, delayed motor milestones, difficulty swallowing or chewing and reduced vital capacity.

Prognosis depends on the age of onset on symptoms with a better prognosis being associated with later onset disease.

McLeod syndrome (or McLeod phenomenon; ) is an X-linked recessive genetic disorder that may affect the blood, brain, peripheral nerves, muscle, and heart. It is caused by a variety of recessively inherited mutations in the XK gene on the X chromosome. The gene is responsible for producing the Kx protein, a secondary supportive protein for the Kell antigen on the red blood cell surface.

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.

The onset of FAC caused by aggregation of the V122I mutation and wild-type TTR, and senile systemic amyloidosis caused by the exclusive aggregation of wild-type TTR, typically occur after age 60. Greater than 40% of these patients present with carpal tunnel syndrome before developing ATTR-CM. Cardiac involvement is often identified with the presence of conduction system disease (sinus node or atrioventricular node dysfunction) and/or congestive heart failure, including shortness of breath, peripheral edema, syncope, exertional dyspnea, generalized fatigue, or heart block. Unfortunately, echocardiographic findings are indistinguishable from those seen in AL amyloidosis, and include thickened ventricular walls (concentric hypertrophy, both right and left) with a normal-to-small left ventricular cavity, increased myocardial echogenicity, normal or mildly reduced ejection fraction (often with evidence of diastolic dysfunction and severe impairment of contraction along the longitudinal axis), and bi-atrial dilation with impaired atrial contraction. Unlike the situation in AL amyloidosis, the ECG voltage is often normal, although low voltage may be seen (despite increased wall thickness on echocardiography). Marked axis deviation, bundle branch block, and AV block are common, as is atrial fibrillation.

Males

In males the symptoms of Danon Disease are more severe. Features of Danon Disease in males are:

- An early age of onset of muscle weakness and heart disease (onset in childhood or adolescence)

- Some learning problems or intellectual disability can be present

- Muscle weakness can be severe and can affect endurance and the ability to walk

- Heart disease (cardiomyopathy) can be severe and can lead to a need for medications. It usually progress to heart failure, commonly complicated by atrial fibrillation and embolic strokes with severe neurological disability, leading to death unless heart transplant is performed.

- Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease.

- Symptoms are usually gradually progressive

- Some individuals may have visual disturbances, and/or retinal pigment abnormalities

- Danon Disease is rare and unfamiliar to most physicians. It can be mistaken for other forms of heart disease and/or muscular dystrophies, including Pompe disease.

Females

In females the symptoms of Danon Disease are less severe. Common symptoms of Danon Disease in females are:

- A later age of onset of symptoms. Many females will not have obvious symptoms until late adolescence or even adulthood.

- Learning problems and intellectual disability are usually ABSENT

- Muscle weakness is often absent or subtle. Some females will tire easily with exercise

- Cardiomyopathy) is often absent in childhood. Some women will develop this in adulthood. Cardiomyopathy can be associated with atrial fibrillation and embolic strokes.

- Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease.

- Symptoms in females progress more slowly than in males.

- Some females may have visual disturbances, and/or retinal pigment abnormalities

- Danon Disease is rare and unfamiliar to most physicians. The milder and more subtle symptoms in females can make it more difficult to diagnose females with Danon Disease

The infantile form usually comes to medical attention within the first few months of life. The usual presenting features are cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%), respiratory distress (78%), muscle weakness (63%), feeding difficulties (57%) and failure to thrive (50%).

The main clinical findings include floppy baby appearance, delayed motor milestones and feeding difficulties. Moderate hepatomegaly may be present. Facial features include macroglossia, wide open mouth, wide open eyes, nasal flaring (due to respiratory distress), and poor facial muscle tone. Cardiopulmonary involvement is manifested by increased respiratory rate, use of accessory muscles for respiration, recurrent chest infections, decreased air entry in the left lower zone (due to cardiomegaly), arrhythmias and evidence of heart failure.

Median age at death in untreated cases is 8.7 months and is usually due to cardiorespiratory failure.

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.

An individual displaying MERRFs syndrome will manifest not only a single symptom, but regularly patients display more than one affected body part at a time. It has been observed that patients with MERRF syndrome will primarily display Myoclonus as a first symptom, along with it they can also manifest seizures, cerebellar ataxia and myopathy. Secondary features include dementia, optic atrophy, bilateral deafness, peripheral neuropathy, spasticity or multiple lipomata. Additional symptoms include dementia, optic atrophy, bilateral deafness and peripheral neuropathy, spasticity, lipomatosis, and/or cardiomyopathy with wolff parkinson-white syndrome. Most patients will not exhibit all of these symptoms, however more than one of these symptoms will be present in a patient who has been diagnosed with MERRFS disease. Due to the multi-symptoms presented by the individual, the severity of the syndrome is very difficult to evaluate. Mitochondrial disorders may present at any age, and this holds truth for MERRS, since it forms part of them. Therefore, if a patient is presenting some of these symptoms, the doctor is able to narrow it down to MEERF mitochondrial disorder.

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)

Danon disease (or glycogen storage disease Type IIb) is a metabolic disorder.Danon disease is an X-linked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability.

Non-compaction cardiomyopathy (NCC), also called spongiform cardiomyopathy, is a rare congenital cardiomyopathy that affects both children and adults. It results from the failure of myocardial development during embryogenesis.

During development, the majority of the heart muscle is a sponge-like meshwork of interwoven myocardial fibers. As normal development progresses, these trabeculated structures undergo significant compaction that transforms them from spongy to solid. This process is particularly apparent in the ventricles, and particularly so in the left ventricle. Noncompaction cardiomyopathy results when there is failure of this process of compaction. Because the consequence of non-compaction is particularly evident in the left ventricle, the condition is also called left ventricular noncompaction. Other hypotheses and models have been proposed, none of which is as widely accepted as the noncompaction model.

Symptoms range greatly in severity. Most are a result of a poor pumping performance by the heart. The disease can be associated with other problems with the heart and the body.

Familial Amyloid Cardiomyopathy (FAC), or Transthyretin Amyloid Cardiomyopathy (ATTR-CM) results from the aggregation and deposition of mutant and wild-type transthyretin (TTR) protein in the heart. TTR amyloid fibrils infiltrate the myocardium, leading to diastolic dysfunction from restrictive cardiomyopathy, and eventual heart failure. Both mutant and wild-type transthyretin comprise the aggregates because the TTR blood protein is a tetramer composed of mutant and wild-type TTR subunits in heterozygotes. Several mutations in TTR are associated with FAC, including V122I, V20I, P24S, A45T, Gly47Val, Glu51Gly, I68L, Gln92Lys, and L111M. One common mutation (V122I), which is a substitution of isoleucine for valine at position 122, occurs with high frequency in African-Americans, with a prevalence of approximately 3.5%. FAC is clinically similar to senile systemic amyloidosis, in which cardiomyopathy results from the aggregation of wild-type transthyretin exclusively.

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.

The symptoms of Freeman–Sheldon syndrome include drooping of the upper eyelids, strabismus, low-set ears, a long philtrum, gradual hearing loss, scoliosis, and walking difficulties. Gastroesophageal reflux has been noted during infancy, but usually improves with age. The tongue may be small, and the limited movement of the soft palate may cause nasal speech. Often there is an H- or Y-shaped dimpling of the skin over the chin.

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).

Patients with acquired non-inflammatory myopathy typically experience weakness, cramping, stiffness, and tetany, most commonly in skeletal muscle surrounding the limbs and upper shoulder girdle.

The most commonly reported symptoms are:

- Muscle fatigue

- Pain

- Muscle spasms and cramps

- Tingling

- Numbness

- Tetany

- Loss of coordination and balance

- Lack of fine and gross motor control

- Muscular wasting and atrophy

Mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) is a rare autosomal recessive mitochondrial disease. It has been previously referred to as polyneuropathy, ophthalmoplegia, leukoencephalopathy, and POLIP syndrome. The disease presents in childhood, but often goes unnoticed for decades. Unlike typical mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, MNGIE is caused by mutations in the TYMP gene, which encodes the enzyme thymidine phosphorylase. Mutations in this gene result in impaired mitochondrial function, leading to intestinal symptoms as well as neuro-ophthalmologic abnormalities. "A secondary form of MNGIE, called MNGIE without leukoencephalopathy, can be caused by mutations in the POLG gene".

Congenital myopathy is a very broad term for any muscle disorder present at birth. This defect primarily affects skeletal muscle fibres and causes muscular weakness and/or hypotonia. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. As a whole, congenital myopathies can be broadly classified as follows:

- A distinctive abnormality in skeletal muscle fibres on the cellular level; observable via light microscope

- Symptoms of muscle weakness and hypotonia

- Is a congenital disorder, meaning it occurs during development and symptoms present themselves at birth or in early life.

- Is a genetic disorder.