If the diagnosis is suspected, serology can be performed:

- One test is for antibodies against the acetylcholine receptor; the test has a reasonable sensitivity of 80–96%, but in ocular myasthenia, the sensitivity falls to 50%.

- A proportion of the patients without antibodies against the acetylcholine receptor have antibodies against the MuSK protein.

- In specific situations, testing is performed for Lambert-Eaton syndrome.

The diagnosis is usually made on electromyography (EMG), which is one of the standard tests in the investigation of otherwise unexplained muscle weakness. This involves the insertion of small needles into the nerves supplying several muscles, administering small electrical impulses through these needles, and measuring the electrical response of the muscle in question. Two EMG investigations can be characteristic in LEMS: compound motor action potentials (CMAPs) and single-fiber examination.

CMAPs show small amplitudes but normal latency and conduction velocities. If repeated impulses are administered (2 per second or 2 Hz), it is normal for CMAP amplitudes to become smaller as the acetylcholine in the motor end plate is depleted. In LEMS, this decrease is larger than observed normally. Eventually, stored acetylcholine is made available, and the amplitudes increase again. In LEMS, this remains insufficient to reach a level sufficient for transmission of an impulse from nerve to muscle; all can be attributed to insufficient calcium in the nerve terminal. A similar pattern is witnessed in myasthenia gravis. In LEMS, in response to exercising the muscle, the CMAP amplitude increases greatly (over 200%, often much more). This also occurs on the administration of a rapid burst of electrical stimuli (20 impulses per second for 10 seconds). This is attributed to the influx of calcium in response to these stimuli. On single-fiber examination, features may include increased jitter (seen in other diseases of neuromuscular transmission) and blocking.

Blood tests may be performed to exclude other causes of muscle disease (elevated creatine kinase may indicate a myositis, and abnormal thyroid function tests may indicate thyrotoxic myopathy). Antibodies against voltage-gated calcium channels can be identified in 85% of people with EMG-confirmed LEMS. Once LEMS is diagnosed, investigations such as a CT scan of the chest are usually performed to identify any possible underlying lung tumors. Around 50–60% of these are discovered immediately after the diagnosis of LEMS. The remainder is diagnosed later, but usually within two years and typically within four years. As a result, scans are typically repeated every six months for the first two years after diagnosis. While CT of the lungs is usually adequate, a positron emission tomography scan of the body may also be performed to search for an occult tumour, particularly of the lung.

During a physical examination to check for MG, a doctor might ask the person to perform repetitive movements. For instance, the doctor may ask one to look at a fixed point for 30 seconds and to relax the muscles of the forehead. This is done because a person with MG and ptosis of the eyes might be involuntarily using the forehead muscles to compensate for the weakness in the eyelids. The clinical examiner might also try to elicit the "curtain sign" in a patient by holding one of the person's eyes open, which in the case of MG will lead the other eye to close.

Congenital myasthenic syndromes (CMS) is "often difficult to diagnose because of a broad differential diagnosis and lack of specific laboratory findings. Identification of the underlying mutation is critical, as certain mutations lead to treatment-responsive conditions while others do not." Whole exome sequencing (WES) is often used as a diagnostic tool that allows for the "initiation of specific treatment".

Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but CMS is not an autoimmune disorder. Instead, CMS is genetic and responds to other forms of drug treatments.

A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors.

Postsynaptic fast-channel CMS (ACh receptors do not stay open long enough) is treated with cholinesterase inhibitors and 3,4-diaminopyridine. In the U.S., the more stable phosphate salt formulation of 3,4-diaminopyridine (amifampyridine phosphate) is under development as an orphan drug for CMS and is available to eligible patients at no cost under an expanded access program by Catalyst Pharmaceuticals.

Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which plugs the ACh receptor.

Ephedrine has been tested on patients in clinical trials and appears to be an effective treatment for DOK7 CMS. Most patients tolerate this type of treatment and improvements in strength can be impressive. Further research must be done in order to determine the long-term response of ephedrine as well as the most effective dosage regimen. Ephedrine can lead to a profound improvement in muscle strength and an even more impressive effect on day-to-day function. The effect of ephedrine is delayed and the improvement occurs over a period of months. Ephedrine was given at doses between 15 and 90 mg/day and as a result, muscle strength improved

Neurotoxin may act on the neuromuscular junction either post synaptically or presynaptically as there are several different forms of toxins that the NMJ is sensitive to.(reference 14) Common mechanisms of action include blockage of acetylcholine release at the synapse thus causing the NMJ to become abnormal in function.(reference 12)

Congenital syndromes affecting the neuromuscular junction are considered a very rare form of disease, occurring in 1 out of 200,000 in the United Kingdom.(reference 29) These are genetically inherited disorders. Symptoms are seen early since the affected individuals carry the mutation from birth. Congenital syndromes are usually classified by the location of the affected gene products. Congenital syndromes can have multiple targets affecting either the presynaptic, synaptic or postsynaptic parts of the neuromuscular junction.(reference 30) For example, if the malfunctioning or inactive protein is acetylcholinesterase, this would be classified as a synapse congenital syndrome.(reference 29)

If LEMS is caused by an underlying cancer, treatment of the cancer usually leads to resolution of the symptoms. Treatment usually consists of chemotherapy, with radiation therapy in those with limited disease.

This condition can be diagnosed by genetic testing. Furthermore, an echocardiogram and X-ray may help in the diagnosis.

Diagnosis is clinical and initially consists of ruling out more common conditions, disorders, and diseases, and usually begins at the general practitioner level. A doctor may conduct a basic neurological exam, including coordination, strength, reflexes, sensation, etc. A doctor may also run a series of tests that include blood work and MRIs.

From there, a patient is likely to be referred to a neurologist or a neuromuscular specialist. The neurologist or specialist may run a series of more specialized tests, including needle electromyography EMG/ and nerve conduction studies (NCS) (these are the most important tests), chest CT (to rule out paraneoplastic) and specific blood work looking for voltage-gated potassium channel antibodies, acetylcholine receptor antibody, and serum immunofixation, TSH, ANA ESR, EEG etc. Neuromyotonia is characterized electromyographically by doublet, triplet or multiplet single unit discharges that have a high, irregular intraburst frequency. Fibrillation potentials and fasciculations are often also present with electromyography.

Because the condition is so rare, it can often be years before a correct diagnosis is made.

NMT is not fatal and many of the symptoms can be controlled. However, because NMT mimics some symptoms of motor neuron disease (ALS) and other more severe diseases, which may be fatal, there can often be significant anxiety until a diagnosis is made. In some rare cases, acquired neuromyotonia has been misdiagnosed as amyotrophic lateral sclerosis (ALS) particularly if fasciculations may be evident in the absence of other clinical features of ALS. However, fasciculations are rarely the first sign of ALS as the hallmark sign is weakness. Similarly, multiple sclerosis has been the initial misdiagnosis in some NMT patients. In order to get an accurate diagnosis see a trained neuromuscular specialist.

Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. The effects of the disease are similar to Lambert-Eaton Syndrome and myasthenia gravis, the difference being that CMS is not an autoimmune disorder.

The differential diagnosis of this condition consists of:

- Hypertrophic cardiomyopathy

- Beckwith-Wiedemann syndrome

- Berardinelli-Seip congenital lipodystrophy

Diagnostic procedures that may reveal muscular disorders include direct clinical observations. This usually starts with the observation of bulk, possible atrophy or loss of muscle tone. Neuromuscular disease can also be diagnosed by testing the levels of various chemicals and antigens in the blood, and using electrodiagnostic medicine tests including electromyography (measuring electrical activity in muscles) and nerve conduction studies.

In neuromuscular disease evaluation, it is important to perform musculoskeletal and neurologic examinations. Genetic testing is an important part of diagnosing inherited neuromuscular conditions.

CCD may be detectable on prenatal ultrasound. After birth, signs in affected babies typically are abdominal distension, visible peristalsis, and watery stools persistent from birth that show chloride loss of more than 90 mmol/l.

An important feature in this diarrhea that helps in the diagnosis, is that it is the only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis.

Neuromyotonia is a type of peripheral nerve hyperexcitability. Peripheral nerve hyperexcitability is an umbrella diagnosis that includes (in order of severity of symptoms from least severe to most severe) benign fasciculation syndrome, cramp fasciculation syndrome, and neuromyotonia. Some doctors will only give the diagnosis of peripheral nerve hyperexcitability as the differences between the three are largely a matter of the severity of the symptoms and can be subjective. However, some objective EMG criteria have been established to help distinguish between the three.

Moreover, the generic use of the term "peripheral nerve hyperexcitability syndromes" to describe the aforementioned conditions is recommended and endorsed by several prominent researchers and practitioners in the field.

Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered α-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown.

Currently there are no official tests or treatments for ROHHAD. Each child has the symptoms above at different ages, yet most symptoms are eventually present. Many children are misdiagnosed or are never diagnosed until alveolar hypoventilation occurs.

Diagnosis of MSS is based on clinical symptoms, magnetic resonance imaging (MRI) of the brain (cerebellar atrophy particularly involving the cerebellar vermis), and muscle biopsy.

It can be associated with mutations of the SIL1 gene, and a mutation can be found in about 50% of cases.

Differential diagnosis includes Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN), Marinesco–Sjögren like syndrome with chylomicronemia, carbohydrate deficient glycoprotein syndromes, Lowe syndrome, and mitochondrial disease.

In terms of treatment for neuromuscular diseases (NMD), "exercise" might be a way of managing them, as NMD individuals would gain muscle strength. In a study aimed at results of exercise, in muscular dystrophy and Charcot-Marie-Tooth disease, the later benefited while the former did not show benefit; therefore, it depends on the disease Other management routes for NMD should be based on medicinal and surgical procedures, again depending on the underlying cause.

The only treatment for MWS is only symptomatic, with multidisciplinary management

Available treatments address the symptoms of CCD, not the underlying defect. Early diagnosis and aggressive salt replacement therapy result in normal growth and development, and generally good outcomes. Replacement of NaCl and KCl has been shown to be effective in children.

A potential treatment is butyrate.

In terms of the diagnosis of arterial tortuosity syndrome can be done via genetic testing, as well as the following listed below:

- CT

- MRI

- Echocardiogram

- Physical exam(for specific characteristics)

No specific treatment is available. Management is only supportive and preventive.

Those who are diagnosed with the disease often die within the first few months of life. Almost all children with the disease die by the age of three.

Treatment for MSS is symptomatic and supportive including physical and occupational therapy, speech therapy, and special education. Cataracts must be removed when vision is impaired, generally in the first decade of life. Hormone replacement therapy is needed if hypogonadism is present.

There have been 30 cases of Marden-Walker Syndrome reported since 1966. The first case of this was in 1966 a female infant was diagnosed with blepharophimosis, joint contractures, arachnodactyly and growth development delay. She ended up passing at 3 months due to pneumonia.

Genetic testing for CHARGE syndrome involves specific genetic testing for the CHD7 gene. The test is available at most major genetic testing laboratories. Insurance companies sometimes do not pay for such genetic tests, though this is changing rapidly as genetic testing is becoming standard across all aspects of medicine. CHARGE syndrome is a clinical diagnosis, which means genetic testing is not required in order to make the diagnosis. Rather, the diagnosis can be made based on clinical features alone.