Treatment is supportive. Hamman's syndrome tends to be benign and self-limiting. It is important to differentiate it from far more serious conditions that have similar symptoms, such as Boerhaave's syndrome.

Macklin described the pathophysiology of Hamman's syndrome to be barotrauma, whereby rupture of alveolar membranes causes a positive pressure gradient of air from the lungs into the mediastinum (the Macklin effect).

Pneumomediastinum is uncommon and occurs when air leaks into the mediastinum. The diagnosis can be confirmed via chest X-ray showing a radiolucent outline around the heart and mediastinum or via CT scanning of the thorax.

Diagnosis of Harlequin syndrome is made when the individual has consistent signs and symptoms of the condition, therefore, it is made by clinical observation. In addition, a neurologist or primary care physician may require an MRI test to rule out similar disorders such as Horner's syndrome, Adie's syndrome, and Ross' syndrome. In an MRI, a radiologist may observe areas near brain or spinal cord for lesions, or any damage to the nerve endings. It is also important that the clinician rules out traumatic causes by performing autonomic function tests. Such tests includes the following: tilt table test, orthostatic blood pressure measurement, head-up test, valsalva maneuver, thermoregulatory sweat test, tendon reflex test, and electrocardiography (ECG). CT scan of the heart and lungs may also be performed to rule out a structural underlying lesion. The medical history of the individual should be carefully noted.

The diagnosis of Boerhaave's syndrome is suggested on the plain chest radiography and confirmed by chest CT scan. The initial plain chest radiograph is almost always abnormal in patients with Boerhaave's syndrome and usually reveals mediastinal or free peritoneal air as the initial radiologic manifestation. With cervical esophageal perforations, plain films of the neck show air in the soft tissues of the prevertebral space.

Hours to days later, pleural effusion(s) with or without pneumothorax, widened mediastinum, and subcutaneous emphysema are typically seen. CT scan may show esophageal wall edema and thickening, extraesophageal air, periesophageal fluid with or without gas bubbles, mediastinal widening, and air and fluid in the pleural spaces, retroperitoneum or lesser sac.

The diagnosis of esophageal perforation could also be confirmed by water-soluble contrast esophagram (Gastrografin), which reveals the location and extent of extravasation of contrast material. Although barium is superior in demonstrating small perforations, the spillage of barium sulfate into the mediastinal and pleural cavities can cause an inflammatory response and subsequent fibrosis and is therefore not used as the primary diagnostic study. If, however, the water-soluble study is negative, a barium study should be performed for better definition.

Endoscopy has no role in the diagnosis of spontaneous esophageal perforation. Both the endoscope and insufflation of air can extend the perforation and introduce air into the mediastinum.

Patients may also have a pleural effusion high in amylase (from saliva), low pH, and may contain particles of food.

Significant cases of subcutaneous emphysema are easy to diagnose because of the characteristic signs of the condition. In some cases, the signs are subtle, making diagnosis more difficult. Medical imaging is used to diagnose the condition or confirm a diagnosis made using clinical signs. On a chest radiograph, subcutaneous emphysema may be seen as radiolucent striations in the pattern expected from the pectoralis major muscle group. Air in the subcutaneous tissues may interfere with radiography of the chest, potentially obscuring serious conditions such as pneumothorax. It can also reduce the effectiveness of chest ultrasound. On the other hand, since subcutaneous emphysema may become apparent in chest X-rays before a pneumothorax does, its presence may be used to infer that of the latter injury. Subcutaneous emphysema can also be seen in CT scans, with the air pockets appearing as dark areas. CT scanning is so sensitive that it commonly makes it possible to find the exact spot from which air is entering the soft tissues. In 1994, M.T. Macklin and C.C. Macklin published further insights into the pathophysiology of spontaneous Macklin's Syndrome occurring from a severe asthmatic attack.

The presence of subcutaneous emphysema in a person who appears quite ill and febrile after bout of vomiting followed by left chest pain is very suggestive of the diagnosis of Boerhaave's syndrome, which is a life-threatening emergency caused by rupture of the distal esophagus.

One possible cause of Harlequin syndrome is a lesion to the preganglionic or postganglionic cervical sympathetic fibers and parasympathetic neurons of the ciliary ganglion. It is also believed that torsion (twisting) of the thoracic spine can cause blockage of the anterior radicular artery leading to Harlequin syndrome. The sympathetic deficit on the denervated side causes the flushing of the opposite side to appear more pronounced. It is unclear whether or not the response of the undamaged side was normal or excessive, but it is believed that it could be a result of the body attempting to compensate for the damaged side and maintain homeostasis.

Since the cause and mechanism of Harlequin syndrome is still unknown, there is no way to prevent this syndrome.

With the exception of a few case reports describing survival without surgery, the mortality of untreated Boerhaave syndrome is nearly 100%. Its treatment includes immediate antibiotic therapy to prevent mediastinitis and sepsis, surgical repair of the perforation, and if there is significant fluid loss it should be replaced with IV fluid therapy since oral rehydration is not possible. Even with early surgical intervention (within 24 hours) the risk of death is 25%.

The tissues in the mediastinum will slowly resorb the air in the cavity so most pneumomediastinums are treated conservatively. Breathing high flow oxygen will increase the absorption of the air.

If the air is under pressure and compressing the heart, a needle may be inserted into the cavity, releasing the air.

Surgery may be needed to repair the hole in the trachea, esophagus or bowel.

If there is lung collapse, it is imperative the affected individual lies on the side of the collapse, although painful, this allows full inflation of the unaffected lung.

Rapid diagnosis and treatment are important in the care of TBI; if the injury is not diagnosed shortly after the injury, the risk of complications is higher. Bronchoscopy is the most effective method to diagnose, locate, and determine the severity of TBI, and it is usually the only method that allows a definitive diagnosis. Diagnosis with a flexible bronchoscope, which allows the injury to be visualized directly, is the fastest and most reliable technique. In people with TBI, bronchoscopy may reveal that the airway is torn, or that the airways are blocked by blood, or that a bronchus has collapsed, obscuring more distal (lower) bronchi from view.

Chest x-ray is the initial imaging technique used to diagnose TBI. The film may not have any signs in an otherwise asymptomatic patient. Indications of TBI seen on radiographs include deformity in the trachea or a defect in the tracheal wall. Radiography may also show cervical emphysema, air in the tissues of the neck. X-rays may also show accompanying injuries and signs such as fractures and subcutaneous emphysema. If subcutaneous emphysema occurs and the hyoid bone appears in an X-ray to be sitting unusually high in the throat, it may be an indication that the trachea has been severed. TBI is also suspected if an endotracheal tube appears in an X-ray to be out of place, or if its cuff appears to be more full than normal or to protrude through a tear in the airway. If a bronchus is torn all the way around, the lung may collapse outward toward the chest wall (rather than inward, as it usually does in pneumothorax) because it loses the attachment to the bronchus which normally holds it toward the center. In a person lying face-up, the lung collapses toward the diaphragm and the back. This sign, described in 1969, is called fallen lung sign and is pathognomonic of TBI (that is, it is diagnostic for TBI because it does not occur in other conditions); however it occurs only rarely. In as many as one in five cases, people with blunt trauma and TBI have no signs of the injury on chest X-ray. CT scanning detects over 90% of TBI resulting from blunt trauma, but neither X-ray nor CT are a replacement for bronchoscopy.

At least 30% of TBI are not discovered at first; this number may be as high as 50%. In about 10% of cases, TBI has no specific signs either clinically or on chest radiography, and its detection may be further complicated by concurrent injuries, since TBI tends to occur after high-energy accidents. Weeks or months may go by before the injury is diagnosed, even though the injury is better known than it was in the past.

In the United States, sarcoidosis has a prevalence of approximately 10 cases per 100,000 whites and 36 cases per 100,000 blacks. Heerfordt syndrome is present in 4.1–5.6% of those with sarcoidosis.

Diagnosis involves consideration of physical features and genetic testing. Presence of split uvula is a differentiating characteristic from Marfan Syndrome, as well as the severity of the heart defects. Loeys-Dietz Syndrome patients have more severe heart involvement and it is advised that they be treated for enlarged aorta earlier due to the increased risk of early rupture in Loeys-Dietz patients. Because different people express different combinations of symptoms and the syndrome was identified in 2005, many doctors may not be aware of its existence, although clinical guidelines were released in 2014-2015. Dr. Harold Dietz, Dr. Bart Loeys, and Dr. Kenneth Zahka are considered experts in this condition.

Carrier testing for Roberts syndrome requires prior identification of the disease-causing mutation in the family. Carriers for the disorder are heterozygotes due to the autosomal recessive nature of the disease. Carriers are also not at risk for contracting Roberts syndrome themselves. A prenatal diagnosis of Roberts syndrome requires an ultrasound examination paired with cytogenetic testing or prior identification of the disease-causing ESCO2 mutations in the family.

Vehicle occupants who wear seat belts have a lower incidence of TBI after a motor vehicle accident. However, if the strap is situated across the front of the neck (instead of the chest), this increases the risk of tracheal injury. Design of medical instruments can be modified to prevent iatrogenic TBI, and medical practitioners can use techniques that reduce the risk of injury with procedures such as tracheotomy.

Subcutaneous emphysema is usually benign. Most of the time, SCE itself does not need treatment (though the conditions from which it results may); however, if the amount of air is large, it can interfere with breathing and be uncomfortable. It occasionally progresses to a state "Massive Subcutaneous Emphysema" which is quite uncomfortable and requires surgical drainage. When the amount of air pushed out of the airways or lung becomes massive, usually due to positive pressure ventilation, the eyelids swell so much that the patient cannot see. Also the pressure of the air may impede the blood flow to the areolae of the breast and skin of the scrotum or labia. This can lead to necrosis of the skin in these areas. The latter are urgent situations requiring rapid, adequate decompression. Severe cases can compress the trachea and do require treatment.

In severe cases of subcutaneous emphysema, catheters can be placed in the subcutaneous tissue to release the air. Small cuts, or "blow holes", may be made in the skin to release the gas. When subcutaneous emphysema occurs due to pneumothorax, a chest tube is frequently used to control the latter; this eliminates the source of the air entering the subcutaneous space. If the volume of subcutaneous air is increasing, it may be that the chest tube is not removing air rapidly enough, so it may be replaced with a larger one. Suction may also be applied to the tube to remove air faster. The progression of the condition can be monitored by marking the boundaries with a special pencil for marking on skin.

Since treatment usually involves dealing with the underlying condition, cases of spontaneous subcutaneous emphysema may require nothing more than bed rest, medication to control pain, and perhaps supplemental oxygen. Breathing oxygen may help the body to absorb the subcutaneous air more quickly.

In terms of diagnosing Bannayan–Riley–Ruvalcaba syndrome there is no current method outside the physical characteristics that may be present as signs/symptoms. There are, however, multiple molecular genetics tests (and cytogenetic test) to determine Bannayan–Riley–Ruvalcaba syndrome.

The diagnosis of this syndrome can be made on clinical examination and perinatal autopsy.

Koenig and Spranger (1986) noted that eye lesions are apparently nonobligatory components of the syndrome. The diagnosis of Fraser syndrome should be entertained in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. Thomas et al. (1986) also emphasized the occurrence of the cryptophthalmos syndrome without cryptophthalmos and proposed diagnostic criteria for Fraser syndrome. Major criteria consisted of cryptophthalmos, syndactyly, abnormal genitalia, and positive family history. Minor criteria were congenital malformation of the nose, ears, or larynx, cleft lip and/or palate, skeletal defects, umbilical hernia, renal agenesis, and mental retardation. Diagnosis was based on the presence of at least 2 major and 1 minor criteria, or 1 major and 4 minor criteria.

Boyd et al. (1988) suggested that prenatal diagnosis by ultrasound examination of eyes, digits, and kidneys should detect the severe form of the syndrome. Serville et al. (1989) demonstrated the feasibility of ultrasonographic diagnosis of the Fraser syndrome at 18 weeks' gestation. They suggested that the diagnosis could be made if 2 of the following signs are present: obstructive uropathy, microphthalmia, syndactyly, and oligohydramnios. Schauer et al. (1990) made the diagnosis at 18.5 weeks' gestation on the basis of sonography. Both the female fetus and the phenotypically normal father had a chromosome anomaly: inv(9)(p11q21). An earlier born infant had Fraser syndrome and the same chromosome 9 inversion.

Van Haelst et al. (2007) provided a revision of the diagnostic criteria for Fraser syndrome according to Thomas et al. (1986) through the addition of airway tract and urinary tract anomalies to the major criteria and removal of mental retardation and clefting as criteria. Major criteria included syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria included anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. Cleft lip and/or palate, cardiac malformations, musculoskeletal anomalies, and mental retardation were considered uncommon. Van Haelst et al. (2007) suggested that the diagnosis of Fraser syndrome can be made if either 3 major criteria, or 2 major and 2 minor criteria, or 1 major and 3 minor criteria are present in a patient.

Cytogenetic preparations that have been stained by either Giemsa or C-banding techniques will show two characteristic chromosomal abnormalities. The first chromosomal abnormality is called premature centromere separation (PCS) and is the most likely pathogenic mechanism for Roberts syndrome. Chromosomes that have PCS will have their centromeres separate during metaphase rather than anaphase (one phase earlier than normal chromosomes). The second chromosomal abnormality is called heterochromatin repulsion (HR). Chromosomes that have HR experience separation of the heterochromatic regions during metaphase. Chromosomes with these two abnormalities will display a "railroad track" appearance because of the absence of primary constriction and repulsion at the heterochromatic regions. The heterochromatic regions are the areas near the centromeres and nucleolar organizers. Carrier status cannot be determined by cytogenetic testing. Other common findings of cytogenetic testing on Roberts syndrome patients are listed below.

- Aneuploidy- the occurrence of one or more extra or missing chromosomes

- Micronucleation- nucleus is smaller than normal

- Multilobulated Nuclei- the nucleus has more than one lobe

In patients that have already been diagnosed with sarcoidosis, Heerfordt syndrome can be inferred from the major symptoms of the syndrome, which include parotitis, fever, and facial nerve palsy. In cases of parotitis, ultrasound-guided biopsy is used to exclude the possibility of lymphoma. There are many possible causes of facial nerve palsy, including Lyme disease, HIV, Melkersson–Rosenthal syndrome, schwannoma, and Bell's palsy. Heerfordt syndrome exhibits spontaneous remission. Treatments for sarcoidosis include corticosteroids and immunosuppressive drugs.

The diagnosis of Perlman syndrome is based on observed phenotypic features and confirmed by histological examination of the kidneys. Prenatal diagnosis is possible for families that have a genetic disposition for Perlman syndrome although there is no conclusive laboratory test to confirm the diagnosis. Fetal overgrowth, particularly with an occipitofrontal circumference (OFC) greater than the 90th centile for gestational age, as well as an excess of amniotic fluid in the amniotic sac (polyhydramnios), may be the first signs of Perlman. Using ultrasound diagnosis, Perlman syndrome has been detected at 18 weeks. During the first trimester, the common abnormalities of the syndrome observed by ultrasound include cystic hygroma and a thickened nuchal lucency. Common findings for the second and third trimesters include macrosomia, enlarged kidneys, renal tumors (both hamartoma and Wilms), cardiac abnormalities and visceromegaly.

Prompt recognition and identification of the disorder along with accurate follow-up and clinical assistance is recommended as the prognosis for Perlman is severe and associated with a high neonatal death rate.

Diagnosis can be made by EEG. In case of epileptic spasms, EEG shows typical patterns.

There is considerable research into the causes, diagnosis and treatments for FGIDs. Diet, microbiome, genetics, neuromuscular function and immunological response all interact. Heightened mast cell activation has been proposed to be a common factor among FGIDs, contributing to visceral hypersensitivity as well as epithelial, neuromuscular, and motility dysfunction.

In terms of the diagnosis of Romano–Ward syndrome the following is done to ascertain the condition(the "Schwartz Score" helps in so doing):

- Exercise test

- ECG

- Family history

About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated. In the United States, termination rates are around 67%, but this rate varied from 61% to 93% among different populations evaluated. When nonpregnant people are asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.

In general, children with a small isolated nevus and a normal physical exam do not need further testing; treatment may include potential surgical removal of the nevus. If syndrome issues are suspected, neurological, ocular, and skeletal exams are important. Laboratory investigations may include serum and urine calcium and phosphate, and possibly liver and renal function tests. The choice of imaging studies depends on the suspected abnormalities and might include skeletal survey, CT scan of the head, MRI, and/or EEG.

Depending on the systems involved, an individual with Schimmelpenning syndrome may need to see an interdisciplinary team of specialists: dermatologist, neurologist, ophthalmologist, orthopedic surgeon, oral surgeon, plastic surgeon, psychologist.