There are rarely any specific tests for the congenital myopathies except for muscle biopsy. Tests can be run to check creatine kinase in the blood, which is often normal or mildly elevated in congenital myopathies. Electromyography can be run to check the electrical activity of the muscle. Diagnosis heavily relies on muscle pathology, where a muscle biopsy is visualised on the cellular level. Diagnosis usually relies on this method, as creatine kinase levels and electromyography can be unreliable and non-specific. Since congenital myopathies are genetic, there have been advancements in prenatal screenings.

A diagnostic test for statin-associated auto-immune necrotizing myopathy will be available soon in order to differentiate between different types of myopathies during diagnosis. The presence of abnormal spontaneous electrical activity in the resting muscles indicates an irritable myopathy and is postulated to reflect the presence of an active necrotising myopathic process or unstable muscle membrane potential. However, this finding has poor sensitivity and specificity for predicting the presence of an inflammatory myopathy on biopsy. Further research into this spontaneous electrical activity will allow for a more accurate differential diagnosis between the different myopathies.

Currently a muscle biopsy remains a critical test, unless the diagnosis can be secured by genetic testing. Genetic testing is a less invasive test and if it can be improved upon that would be ideal. Molecular genetic testing is now available for many of the more common metabolic myopathies and muscular dystrophies. These tests are costly and are thus best used to confirm rather than screen for a diagnosis of a specific myopathy. Due to the cost of these tests, they are best used to confirm rather than screen for a diagnosis of a specific myopathy. It is the hope of researchers that as these testing methods improve in function, both costs and access will become more manageable

The increased study of muscle pathophysiology is of importance to researchers as it helps to better differentiate inflammatory versus non-inflammatory and to aim treatment as part of the differential diagnosis. Certainly classification schemes that better define the wide range of myopathies will help clinicians to gain a better understanding of how to think about these patients. Continued research efforts to help appreciate the pathophysiology will improve clinicians ability to administer the most appropriate therapy based on the particular variety of myopathy.

The mechanism for myopathy in individuals with low vitamin D is not completely understood. A decreased availability of 250HD leads to mishandling of cellular calcium transport to the sarcoplasmic reticulum and mitochondria, and is associated with reduced actomyosin content of myofibrils.

The subtypes of congenital muscular dystrophy have been established through variations in multiple genes. It should be noted that phenotype, as well as, genotype classifications are used to establish the subtypes, in some literature.

One finds that congenital muscular dystrophies can be either autosomal dominant or autosomal recessive in terms of the inheritance pattern, though the latter is much more common

Individuals who suffer from congenital muscular dystrophy fall into one of the following "types":

For the diagnosis of congenital muscular dystrophy, the following tests/exams are done:

- Lab study (CK levels)

- MRI (of muscle, and/or brain)

- EMG

- Genetic testing

The conditions included under the term "congenital myopathy" can vary. One source includes nemaline myopathy, myotubular myopathy, central core myopathy, congenital fiber type disproportion, and multicore myopathy. The term can also be used more broadly, to describe conditions present from birth.

Electrophysiological evidence of denervation with intact motor and sensory nerve conduction findings must be made by using nerve conduction studies, usually in conjunction with EMG. The presence of polyphasic potentials and fibrillation at rest are characteristic of congenital dSMA.

The following are useful in diagnosis:

- Nerve conduction studies (NCS), to test for denervation

- Electromyography (EMG), also to detect denervation

- X-ray, to look for bone abnormalities

- Magnetic resonance imaging (MRI)

- Skeletal muscle biopsy examination

- Serum creatine kinase (CK) level in blood, usually elevated in affected individuals

- Pulmonary function test

During vigorous ischemic exercise, skeletal muscle functions aerobically, generating lactate and ammonia a coproduct of muscle myoadenylate deaminase (AMPD) activity. The forearm ischemic exercise test takes advantage of this physiology and has been standardized to screen for disorders of glycogen metabolism and AMPD deficiency. Patients with a glycogen storage disease manifest a normal increase in ammonia but no change from baseline of lactate, whereas in those with AMPD deficiency, lactate levels increase but ammonia levels do not. If ischemic exercise testing gives an abnormal result, enzyme analysis must be performed on muscle to confirm the putative deficiency state because false-positive results can occur.

The diagnosis of Emery–Dreifuss muscular dystrophy can be established via single-gene testing or genomic testing, and clinically diagnosed via the following exams/methods:

DMD is carried by an X-linked recessive gene. Males have only one X chromosome, so one copy of the mutated gene will cause DMD. Fathers cannot pass X-linked traits on to their sons, so the mutation is transmitted by the mother.

If the mother is a carrier, and therefore one of her two X chromosomes has a DMD mutation, a 50% chance exists that a female child will inherit that mutation as one of her two X chromosomes, and be a carrier. If that carrier has a male child, there is a 50% chance that he will inherit the X chromosome with the mutation, and will have DMD. Prenatal tests can tell whether the unborn child has the most common mutations. Many mutations are responsible for DMD, and some have not been identified, so genetic testing only works when family members with DMD have an identified mutation.

Prior to invasive testing, determination of the fetal sex is important; while males are sometimes affected by this X-linked disease, female DMD is extremely rare. This can be achieved by ultrasound scan at 16 weeks or more recently by free fetal DNA testing. Chorion villus sampling (CVS) can be done at 11–14 weeks, and has a 1% risk of miscarriage. Amniocentesis can be done after 15 weeks, and has a 0.5% risk of miscarriage. Fetal blood sampling can be done around 18 weeks. Another option in the case of unclear genetic test results is fetal muscle biopsy.

Since the early 2000s, genetic testing that measures the size of the D4Z4 deletions on 4q35 has become the preferred mechanism for confirming the presence of FSHD. As of 2007, this test is considered highly accurate but is still performed by a limited set of labs in the US, such as Athena diagnostics under test code 405. However, because the test is expensive, patients and doctors may still rely on one or more of the following tests, all of which are far less accurate and specific than the genetic test:

- Creatine kinase (CK) level: This test measures the Creatine kinase enzyme in the blood. Elevated levels of CK are related to muscle atrophy.

- electromyogram (EMG): This test measures the electrical activity in the muscle

- nerve conduction velocity (NCV): This test measures the how fast signals travel from one part of a nerve to another. The nerve signals are measured with surface electrodes (similar to those used for an electrocardiogram), and the test is only slightly uncomfortable.

- muscle biopsy: Through outpatient surgery a small piece of muscle is removed (usually from the arm or leg) and evaluated with a variety of biochemical tests. Researchers are attempting to match results of muscle biopsies with DNA tests to better understand how variations in the genome present themselves in tissue anomalies.

In terms of diagnosis of Fukuyama congenital muscular dystrophy, serum creatine kinase concentration and muscle biopsies can be obtained to help determine if the individual has FMCD. FKTN molecular genetic testing is used to determine a mutation in the FKTN gene after a serum creatine kinase concentration, muscle biopsies, and/or MRI imaging have presented abnormalities indicative of FCMD, the presence of the symptoms indicates Fukuyama congenital muscular dystrophy. The available genetic test include:

- Linkage analysis

- Deletion analysis

- Sequence analysis - exons

- Sequence analysis - entire coding region

If DNA testing fails to find the mutation, a muscle biopsy test may be performed. A small sample of muscle tissue is extracted using a biopsy needle. The key tests performed on the biopsy sample for DMD are immunocytochemistry and immunoblotting for dystrophin, and should be interpreted by an experienced neuromuscular pathologist. These tests provide information on the presence or absence of the protein. Absence of the protein is a positive test for DMD. Where dystrophin is present, the tests indicate the amount and molecular size of dystrophin, helping to distinguish DMD from milder dystrophinopathy phenotypes. Over the past several years, DNA tests have been developed that detect more of the many mutations that cause the condition, and muscle biopsy is not required as often to confirm the presence of DMD.

The usual initial investigations include chest X ray, electrocardiogram and echocardiography. Typical findings are those of an enlarged heart with non specific conduction defects. Biochemical investigations include serum creatine kinase (typically increased 10 fold) with lesser elevations of the serum aldolase, aspartate transaminase, alanine transaminase and lactic dehydrogenase. Diagnosis is made by estimating the acid alpha glucosidase activity in either skin biopsy (fibroblasts), muscle biopsy (muscle cells) or in white blood cells. The choice of sample depends on the facilities available at the diagnostic laboratory.

In the late onset form, the findings on investigation are similar to those of the infantile form with the caveat that the creatinine kinases may be normal in some cases. The diagnosis is by estimation of the enzyme activity in a suitable sample.

On May 17, 2013 the Secretary's Discretionary Advisory Committee on Heritable Diseases in Newborns and Children (DACHDNC) approved a recommendation to the Secretary of Health and Human Services to add Pompe to the Recommended Uniform Screening Panel (RUSP). The HHS secretary must first approve the recommendation before the disease is formally added to the panel.

The types of Emery–Dreifuss muscular dystrophy are distinguished by their pattern of inheritance: X-linked, autosomal dominant, and autosomal recessive.

- Autosomal dominant "Emery–Dreifuss muscular dystrophy" individuals experience heart problems with weakness (and wasting) of skeletal muscles and Achilles tendon contractures.

- X-linked "Emery–Dreifuss muscular dystrophy" is the result of the EMD gene, with cardiac involvement and some mental retardation.

- Autosomal recessive individuals with this type of the disorder demonstrate cardiac issues, such as arrhythmia. Individuals who acquire EDMD via the autosomal recessive route have an incidence of 1 in 300,000.

Congenital dSMA has a relatively stable disease course, with disability mainly attributed to increased contractures rather than loss of muscle strength. Individuals frequently use crutches, knee, ankle, and/or foot orthoses, or wheelchairs. Orthopaedic surgery can be an option for some patients with severely impaired movement. Physical therapy and occupational therapy can help prevent further contractures from occurring, though they do not reverse the effects of preexisting ones. Some literature suggests the use of electrical stimulation or botulinum toxin to halt the progression of contractures.

The diagnosis is made on the combination of typical symptoms and the appearance on biopsy (tissue sample) from muscle. The name derives from the typical appearance of the biopsy on light microscopy, where the muscle cells have cores that are devoid of mitochondria and specific enzymes.

Respiratory insufficiency develops in a small proportion of cases. Creatine kinase and electromyography (EMG) tend to be normal.

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.

A genetic test is available for Type 1 PSSM. This test requires a blood or hair sample, and is less-invasive than muscle biopsy. However, it may be less useful for breeds that are more commonly affected by Type 2 PSSM, such as light horse breeds. Often a muscle biopsy is recommended for horses displaying clinical signs of PSSM but who have negative results for GYS1 mutation.

A muscle biopsy may be taken from the semimembranosis or semitendinosis (hamstring) muscles. The biopsy is stained for glycogen, and the intensity of stain uptake in the muscle, as well as the presence of any inclusions, helps to determine the diagnosis of PSSM. This test is the only method for diagnosing Type 2 PSSM. Horses with Type 1 PSSM will usually have between 1.5-2 times the normal levels of glycogen in their skeletal muscle. While abnormalities indicating muscle damage can be seen on histologic sections of muscle as young as 1 month of age, abnormal polysaccharide accumulation may take up to 3 years to develop.

There are exceptions, but levels of alpha-glucosidase determines the type of GSD II an individual may have. More alpha glucosidase present in the individuals muscles means symptoms occur later in life and progress more slowly. GSD II is broadly divided into two onset forms based on the age symptoms occur.

Infantile-onset form is usually diagnosed at 4–8 months; muscles appear normal but are limp and weak preventing them from lifting their head or rolling over. As the disease progresses heart muscles thicken and progressively fail. Without treatment death usually occurs due to heart failure and respiratory weakness.

Late or later onset form occurs later than one to two years and progresses more slowly than Infantile-onset form. One of the first symptoms is a progressive decrease in muscle strength starting with the legs and moving to smaller muscles in the trunk and arms, such as the diaphragm and other muscles required for breathing. Respiratory failure is the most common cause of death. Enlargement of the heart muscles and rhythm disturbances are not significant features but do occur in some cases.

At present, Nemaline myopathy does not have a cure. Nemaline myopathy is a very rare disease that only effects 1 out of 50,000 on average, although recent studies show that this number is even smaller. There are a number of treatments to minimize the symptoms of the disease. The treatments and procedures to help patients with nemaline myopathy vary depending on the severity of the disease. A possible accommodation could be the use of a stabilizer, such as a brace. Other means include moderate stretching and moderate exercise to help target muscles maintain maximum health.

As people with NM grow and develop throughout their lives, it is important for them to see a variety of health professionals regularly, including a neurologist, physical therapist, and others, such as speech therapists and psychologists, to help both the patient and family adjust to everyday life.

Some cases of myotonia congenita do not require treatment, or it is determined that the risks of the medication outweigh the benefits. If necessary, however, symptoms of the disorder may be relieved with quinine, phenytoin, carbamazepine, mexiletine and other anticonvulsant drugs. Physical therapy and other rehabilitative measures may also be used to help muscle function. Genetic counseling is available.

Fukuyama congenital muscular dystrophy has a poor prognosis. Most children with FCMD reach a maximum mobility at sitting upright and sliding. Due to the compounded effects of continually worsening heart problems, impaired mental development, problems swallowing and additional complications, children with FCMD rarely live through adolescence, the disorder proves fatal by age 20.

There is some laboratory tests that may aid in diagnosis of GSD-V. A muscle biopsy will note the absence of myophosphorylase in muscle fibers. In some cases, acid-Schiff stained glycogen can be seen with microscopy.

Genetic sequencing of the PYGM gene (which codes for the muscle isoform of glycogen phosphorylase) may be done to determine the presence of gene mutations, determining if McArdle's is present. This type of testing is considerably less invasive than a muscle biopsy.

The physician can also perform an ischemic forearm exercise test as described above. Some findings suggest a nonischemic test could be performed with similar results. The nonischemic version of this test would involve not cutting off the blood flow to the exercising arm. Findings consistent with McArdle’s disease would include a failure of lactate in venous blood and exaggerated ammonia levels. These findings would indicate a severe muscle glycolytic block. Ammonia arises from the impaired buffering of ADP, which leads to an increase in AMP concentration resulting in an increase in AMP deamination.

Physicians may also check resting levels of creatine kinase, which are moderately increased in 90% of patients. In some, the level is increased by multitudes - a person without GSD-V will have a CK between 60 and 400IU/L, while a person with the syndrome may have a level of 5,000 IU/L at rest, and may increase to 35,000 IU/L or more with muscle exertion. This can help distinguish McArdle's syndrome from carnitine palmitoyltransferase II deficiency (CPT-II), a lipid-based metabolic disorder which prevents fatty acids from being transported into mitochondria for use as an energy source. Also, serum electrolytes and endocrine studies (such as thyroid function, parathyroid function and growth hormone levels) will also be completed. Urine studies are required only if rhabdomyolysis is suspected. Urine volume, urine sediment and myoglobin levels would be ascertained. If rhabdomyolysis is suspected, serum myoglobin, creatine kinase, lactate dehydrogenase, electrolytes and renal function will be checked.

Outbreaks may be measurable clinically by elevated levels of alkaline phosphatase and bone-specific alkaline phosphatase.

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.