De Quervain syndrome is diagnosed clinically, based on history and physical examination, though diagnostic imaging such as x-ray may be used to rule out fracture, arthritis, or other causes, based on the patient's history and presentation. Finkelstein's test is a physical exam maneuver used to diagnose de Quervain syndrome. To perform the test, the examiner grasps the thumb and sharply deviates the hand toward the ulnar side. If sharp pain occurs along the distal radius (top of forearm, about an inch below the wrist), de Quervain's syndrome is likely. While a positive Finkelstein's test is often considered pathognomonic for de Quervain syndrome, the maneuver can also cause pain in those with osteoarthritis at the base of the thumb.

Differential diagnoses include:

1. Osteoarthritis of the first carpo-metacarpal joint

2. Intersection syndrome—pain will be more towards the middle of the back of the forearm and about 2–3 inches below the wrist

3. Wartenberg's syndrome

RSIs are assessed using a number of objective clinical measures. These include effort-based tests such as grip and pinch strength, diagnostic tests such as Finkelstein's test for De Quervain's tendinitis, Phalen's Contortion, Tinel's Percussion for carpal tunnel syndrome, and nerve conduction velocity tests that show nerve compression in the wrist. Various imaging techniques can also be used to show nerve compression such as x-ray for the wrist, and MRI for the thoracic outlet and cervico-brachial areas.

As with many musculoskeletal conditions, the management of de Quervain's disease is determined more by convention than scientific data. From the original description of the illness in 1895 until the first description of corticosteroid injection by Jarrod Ismond in 1955, it appears that the only treatment offered was surgery. Since approximately 1972, the prevailing opinion has been that of McKenzie (1972) who suggested that corticosteroid injection was the first line of treatment and surgery should be reserved for unsuccessful injections. A systematic review and meta-analysis published in 2013 found that corticosteroid injection seems to be an effective form of conservative management of de Quervain's syndrome in approximately 50% of patients, although more research is needed regarding the extent of any clinical benefits. Efficacy data are relatively sparse and it is not clear whether benefits affect the overall natural history of the illness.

Most tendinoses are self-limiting and the same is likely to be true of de Quervain's although further study is needed.

Palliative treatments include a splint that immobilized the wrist and the thumb to the interphalangeal joint and anti-inflammatory medication or acetaminophen. Systematic review and meta-analysis do not support the use of splinting over steroid injections.

Surgery (in which the sheath of the first dorsal compartment is opened longitudinally) is documented to provide relief in most patients. The most important risk is to the radial sensory nerve.

Some occupational and physical therapists suggest alternative lifting mechanics based on the theory that the condition is due to repetitive use of the thumbs during lifting. Physical/Occupational therapy can suggest activities to avoid based on the theory that certain activities might exacerbate one's condition, as well as instruct on strengthening exercises based on the theory that this will contribute to better form and use of other muscle groups, which might limit irritation of the tendons.

Some occupational and physical therapists use other treatments, in conjunction with Therapeutic Exercises, based on the rationale that they reduce inflammation and pain and promote healing: UST, SWD, or other deep heat treatments, as well as TENS, acupuncture, or infrared light therapy, and cold laser treatments. However, the pathology of the condition is not inflammatory changes to the synovial sheath and inflammation is secondary to the condition from friction. Teaching patients to reduce their secondary inflammation does not treat the underlying condition but may reduce their pain; which is helpful when trying to perform the prescribed exercise interventions.

Getting Physical Therapy before surgery or injections has been shown to reduce overall costs to patients and is a viable option to treat a wide array of musculoskeletal injuries.

CMC OA is diagnosed based on clinical findings and radiologic imaging.

The most-often prescribed treatments for early-stage RSIs include analgesics, myofeedback, biofeedback, physical therapy, relaxation, and ultrasound therapy. Low-grade RSIs can sometimes resolve themselves if treatments begin shortly after the onset of symptoms. However, some RSIs may require more aggressive intervention including surgery and can persist for years.

General exercise has been shown to decrease the risk of developing RSI. Doctors sometimes recommend that RSI sufferers engage in specific strengthening exercises, for example to improve sitting posture, reduce excessive kyphosis, and potentially thoracic outlet syndrome. Modifications of posture and arm use (human factors and ergonomics) are often recommended.

Diagnosis of tenosynovitis is typically made clinically after a thorough patient history and physical exam. Aspirated fluid can also be cultured to identify the infectious organism. X-rays are typically unremarkable but can help rule out a broken bone or a foreign body

There is moderate quality evidence that manual therapy and therapeutic exercise improves pain in patients with thumb CMC

OA at both short- and intermediate-term follow-up, and low to moderate quality evidence that magneto therapy improves pain

and function at short-term follow-up. There is moderate evidence that orthoses (splints) can improve hand function at long-term follow-up. There is very low to low-quality evidence that other conservative interventions provide no significant improvement in pain and in function at short- and long-term follow-up. Some of the commonly performed conservative interventions performed in therapy have evidence to support their use to improve hand function and decrease hand pain in patients with CMC OA.

The mainstay of treatment for tenosynovitis includes symptom alleviation, antibiotic therapy, and surgery. Mild tenosynovitis causing small scale swelling can be treated with non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and as an analgesic. Resting the affected tendons is essential for recovery; a brace is often recommended. Physical or occupational therapy may also be beneficial in reducing symptoms.

Most infectious tenosynovitis cases should be managed with tendon sheath irrigation and drainage, with or without debridement of surrounding necrotic tissue, along with treatment with broad-spectrum antibiotics. In severe cases, amputation may even be necessary to prevent the further spread of infection. Following surgical intervention, antibiotic therapy is continued and adjusted based on the results of the fluid culture.

Blood tests show a high concentration of specific gamma-globulins (monoclonal gammopathy) of the IgM type. It almost always has light chains of the κ-type. A variant in which IgG is raised has been described, which appears to be ten times as rare. The immunoglobulins may show up in the urine as Bence Jones proteins. Signs of inflammation are often present: these include an increased white blood cell count (leukocytosis) and a raised erythrocyte sedimentation rate and C-reactive protein. There can be anemia of chronic disease. Bone abnormalities can be seen on radiological imaging (often increased density or osteosclerosis) or biopsy.

Because it is such a rare condition (as of September 2014, only 281 cases have been reported), it is important to rule out other conditions which can cause periodic fevers, paraproteins or chronic hives. These include (and are not limited to) autoimmune or autoinflammatory disorders such as adult-onset Still's disease, angioedema, hematological disorders such as lymphoma or monoclonal gammopathy of undetermined significance, other causes of hives, cryoglobulinemia, mastocytosis, chronic neonatal onset multisystem inflammatory disease or Muckle–Wells syndrome.

It is however possible to have more than one rare condition as seen by a patient with Schnitzler's syndrome and cold induced urticaria.

A meeting of experts, including Dr Liliane Schnitzler (then retired) took place in Strasbourg in May 2012 and drew up diagnostic criteria known as the "Strasbourg Criteria". These included two obligate criteria (chronic urticarial rash and monoclonal IgM or IgG) and several minor criteria; a definite diagnosis requires the two obligate criteria and two minor criteria if IgM, three if IgG; a probable diagnosis requires the two obligate criteria and one (IgM) or two (IgG) minor criteria.

The life span in patients with Schnitzler syndrome has not been shown to differ much from the general population. Careful follow-up is advised, however. A significant proportion of patients develops a lymphoproliferative disorder as a complication, most commonly Waldenström's macroglobulinemia. This may lead to symptoms of hyperviscosity syndrome. AA amyloidosis has also been reported in people with Schnitzler syndrome.

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.

It is possible to detect the signs of Alexander disease with magnetic resonance imaging (MRI), which looks for specific changes in the brain that may be tell-tale signs for the disease. It is even possible to detect adult-onset Alexander disease with MRI. Alexander disease may also be revealed by genetic testing for the known cause of Alexander disease. A rough diagnosis may also be made through revealing of clinical symptoms including, enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.

The diagnosis of CdLS is primarily a clinical one, based on medical signs that are evident in a medical history, physical examination, and laboratory tests. Since 2006, testing for NIPBL and SMC1A has been available through the University of Chicago. This is best accomplished through a referral to a genetics specialist or clinic.

CdLS is thought to be underdiagnosed and frequently misdiagnosed.

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.

The prognosis is generally poor. With early onset, death usually occurs within 10 years from the onset of symptoms. Individuals with the infantile form usually die before the age of 7. Usually, the later the disease occurs, the slower its course is.

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.

Prognosis strongly depends on which subtype of disease it is. Some are deadly in infancy but most are late onset and mostly manageable.

There is no diagnostic test for alternating hemiplegia, which makes it very difficult to diagnose. Also, because alternating hemiplegia is extremely rare, it is frequently missed and the patient is often misdiagnosed. Proper diagnosis, however, is critical for early treatment of the disorder. There are many criteria that can help in the proper general diagnosis of alternating hemiplegia.

The Cornelia de Lange Syndrome (CdLS) Foundation is a nonprofit, family support organization based in Avon, Connecticut, that exists to ensure early and accurate diagnosis of CdLS, promote research into the causes and manifestations of the syndrome, and help people with a diagnosis of CdLS, and others with similar characteristics, make informed decisions throughout their lives.

Weber's syndrome is the only form of alternating hemiplegia that is somewhat easy to diagnose beyond the general criteria. Although Weber's syndrome is rare, a child born with the disorder typically has a port-wine stain on the face around the eye. While the port-wine stain does not necessarily mean the child has Weber's syndrome, if the port-wine stain involves the ophthalmic division of the trigeminal nerve than the likelihood of it being weber's syndrome greatly increases. If a port-wine stain around the eye is found, the patient should be screened for intracranial leptomeningeal angiomatosis. Magnetic resonance imaging (MRI)can be used to determine the presence and severity while computed cranial tomography can be used to determine the effect. MRI is the preferred diagnostic test on children presenting with port-wine stain. Other imaging techniques can be used in addition to further determine the severity of the disorder. The initial diagnosis is made based on the presence of neurologic and ophthalmic disease but the disease progresses differently in each patient so after initial diagnosis the patient should be monitored frequently in order to handle further complications resulting from the syndrome.

Diagnosis is based on the distinctive cry and accompanying physical problems. These common symptoms are quite easily observed in infants. Affected children are typically diagnosed by a doctor or nurse at birth. Genetic counseling and genetic testing may be offered to families with individuals who have cri du chat syndrome. Prenatally the deletion of the cri du chat related region in the p arm of chromosome 5 can be detected from amniotic fluid or chorionic villi samples with BACs-on-Beads technology. G-banded karyotype of a carrier is also useful. Children may be treated by speech, physical and occupational therapists. Heart abnormalities often require surgical correction.

There is currently no cure for the disease but treatments to help the symptoms are available.

The detection of tumours specific to VHL disease is important in the disease's diagnosis. In individuals with a family history of VHL disease, one hemangioblastoma, pheochromocytoma or renal cell carcinoma may be sufficient to make a diagnosis. As all the tumours associated with VHL disease can be found sporadically, at least two tumours must be identified to diagnose VHL disease in a person without a family history.

Genetic diagnosis is also useful in VHL disease diagnosis. In hereditary VHL, disease techniques such as southern blotting and gene sequencing can be used to analyse DNA and identify mutations. These tests can be used to screen family members of those afflicted with VHL disease; "de novo" cases that produce genetic mosaicism are more difficult to detect because mutations are not found in the white blood cells that are used for genetic analysis.

Respiratory complications are often cause of death in early infancy.

Marshall–Smith syndrome is not to be confused with:

- Marshall syndrome (aka.Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome, see also: Periodic fever syndrome)

- Sotos (like) syndrome

- Weaver-Smith syndrome (WSS)