Familial dysautonomia is inherited in an autosomal recessive pattern, which means 2 copies of the gene in each cell are altered. If both parents are shown to be carriers by genetic testing, there is a 25% chance that the child will produce FD. Prenatal diagnosis for pregnancies at increased risk for FD by amniocentesis (for 14–17 weeks) or chorionic villus sampling (for 10–11 weeks) is possible.

Prenatal screening is not typically done for FHM, however it may be performed if requested. As penetrance is high, individuals found to carry mutations should be expected to develop signs of FHM at some point in life.

Genetic testing is performed on a small sample of blood from the tested individual. The DNA is examined with a designed probe specific to the known mutations. The accuracy of the test is above 99%. Dr. Anat Blumenfeld of the Hadasah Medical center in Jerusalem identified chromosome number 9 as the responsible chromosome.

Diagnosis of FHM is made according to the following criteria:

- Two attacks of each of the following:

- At least one close (first or second degree) relative with FHM

- No other likely cause

Sporadic forms follow the same diagnostic criteria, with the exception of family history.

In all cases, family and patient history is used for diagnosis. Brain imaging techniques, such as MRI, CAT scans and SPECT, are used to look for signs of other familial conditions such as CADASIL or mitochondrial disease, and for evidence of cerebellar degeneration. With the discovery of causative genes, genetic sequencing can also be used to verify diagnosis (though not all genetic loci are known).

Clinical features along with the familial tendency may be enough to make a diagnosis. Genetic testing may also be used.

Diagnosis usually occurs upon investigation of a cause for already suspected Cushing's syndrome. High levels of cortisol observed in patients with PPNAD are not suppressed upon administration of dexamethasone (dexamethasone suppression test), and upon MRI or CT imaging, the pituitary will show no abnormalities. Measuring ACTH will confirm that the cause of the patients Cushing's syndrome is ACTH independent. The nature of Cushing's syndrome itself is periodic, which can make diagnosing PPNAD increasingly difficult.

Diagnosis of PPNAD can be difficult to determine preoperatively as CT scan findings can be variable ie appear normal or suggest unilateral adrenal lesions therefore impeding the correct diagnosis. NP-59 scintigraphy may be particularly useful in identifying the bilateral nature of the disease.

Gene studies are not necessary for diagnosis as there are clear gross and histological diagnostic markers, as the nodules can usually be seen clearly in both cases A positive family history of PPNAD has been shown to be associated with abnormal histological findings, e.g. mitotic figures, which may further hinder diagnosis. At the point where abdominal CT scanning and pituitary fossa MRI show no clear abnormalities, adrenalectomy may be performed.

Most infants with infantile cortical hyperostosis are diagnosed by physical examination. X-rays can confirm the presence of bone changes and soft tissue swelling. Biopsy of the affected areas can confirm the presence of typical histopathological changes. No specific blood tests exist, but tests such as erythrocyte sedimentation rate (ESR) and alkaline phosphatase levels are often elevated. A complete blood count may show anemia (low red blood cell count) and leukocytosis (high white blood cell count). Other tests may be done to help exclude other diagnoses. Ultrasound imaging can help diagnose prenatal cases.

Canakinumab has been approved for treatment of HIDS and has shown to be effective. The immunosuppressant drugs etanercept and anakinra have also shown to be effective. Statin drugs might decrease the level of mevalonate and are presently being investigated. A recent single case report highlighted bisphosphonates as a potential therapeutic option.

Osteomyelitis (bone infection), which is much more common than infantile cortical hyperostosis, must be excluded, since it requires urgent treatment. Other diagnoses that can mimic this disorder and need to be excluded include physical trauma, child abuse, Vitamin A excess, hyperphosphatemia, prostaglandin E1 and E2 administration, scurvy, infections (including syphilis), Ewing sarcoma, and metastatic neuroblastoma.

Henri Gougerot and Alexandre Carteaud originally described the condition in 1927. The cause remains unknown, but the observation that the condition may clear with Minocycline turned attention to an infectious agent. "Actinomycete Dietzia" strain X was isolated from one individual. Other antibiotics found useful include azithromycin, fusidic acid, clarithromycin, erythromycin, tetracycline and cefdinir.

While the term pemphigus typically refers to "a rare group of blistering autoimmune diseases" affecting "the skin and mucous membranes", Hailey–Hailey disease is not an autoimmune disorder and there are no autoantibodies. According to Pemphigus Pemphigoid Foundation (IPPF), "familial benign chronic pemphigus, or Hailey-Hailey disease, is a different condition from Pemphigus".

Confluent and reticulated papillomatosis of Gougerot and Carteaud (also known as "Confluent and reticulated papillomatosis," "CRP", "CARP", "Familial cutaneous papillomatosis," and "Familial occurrence of confluent and reticulated papillomatosis") is an uncommon but distinctive acquired ichthyosiform dermatosis characterized by persistent dark, scaly, papules and plaques that tend to be localized predominantly on the central trunk.

Lipomatosis is believed to be an autosomal dominant condition in which multiple lipomas are present on the body. Many discrete, encapsulated lipomas form on the trunk and extremities, with relatively few on the head and shoulders. In 1993, a genetic polymorphism within lipomas was localized to chromosome 12q15, where the HMGIC gene encodes the high-mobility-group protein isoform I-C. This is one of the most commonly found mutations in solitary lipomatous tumors but lipomas often have multiple mutations. Reciprocal translocations involving chromosomes 12q13 and 12q14 have also been observed within.

Although this condition is benign, it can sometimes be very painful depending on location of the lipomas. Some patients who are concerned with cosmetics seek removal of individual lipomas. Removal can include simple excision, endoscopic removal, or liposuction.

Other entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, benign symmetric lipomatosis (Madelung disease),Dercum's Disease, familial lipodystrophy, hibernomas, epidural steroid injections with epidural lipomatosis, and familial angiolipomatosis.

There are several distinct urticarial syndromes including:

- Muckle–Wells syndrome

- Familial Mediterranean fever

- Systemic capillary leak syndrome

The current (2008) diagnostic criteria for HLH are

1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11.

OR

2. Fulfillment of five out of the eight criteria below:

- Fever (defined as a temperature >100.4 °F, >38 °C)

- Enlargement of the spleen

- Decreased blood cell counts affecting at least two of three lineages in the peripheral blood:

- Haemoglobin <9 g/100 ml (in infants <4 weeks: haemoglobin <10 g/100 ml) (anemia)

- Platelets <100×10/L (thrombocytopenia)

- Neutrophils <1×10/L (neutropenia

- High blood levels of triglycerides (fasting, greater than or equal to 265 mg/100 ml) and/or decreased amounts of fibrinogen in the blood (≤ 150 mg/100 ml)

- Ferritin ≥ 500 ng/ml

- Haemophagocytosis in the bone marrow, spleen or lymph nodes

- Low or absent natural killer cell activity

- Soluble CD25 (soluble IL-2 receptor) >2400 U/ml (or per local reference laboratory)

In addition, in the case of familial HLH, no evidence of malignancy should be apparent.

It should be noted that not all five out of eight criteria are required for diagnosis of HLH in adults, and a high index of suspicion is required for diagnosis as delays results in increased mortality. The diagnostic criteria were developed in pediatric populations and have not been validated for adult HLH patients. Attempts to improve diagnosis of HLH have included use of the HScore, which can be used to estimate an individual's risk of HLH.

The blood count typically shows decreased numbers of blood cells—including a decreased amount of circulating red blood cells, white blood cells, and platelets.

The bone marrow may show hemophagocytosis.

The liver function tests are usually elevated. A low level of the protein albumin in the blood is common.

The serum C reactive protein, erythrocyte sedimentation rate, and ferritin level are markedly elevated. In children, a ferritin above 10000 is very sensitive and specific for the diagnosis of HLH, however, the diagnostic utility for ferritin is less for adult HLH patients.

The serum fibrinogen level is usually low and the D-dimer level is elevated.

The sphingomyelinase is elevated.

Bone marrow biopsy shows histiocytosis.

Linear focal elastosis (also known as "Elastotic striae") presents with asymptomatic, palpable or atrophic, yellow lines of the middle and lower back, thighs, arms and breasts.

Granulosis rubra nasi is a rare familial disease of children, occurring on the nose, cheeks, and chin, characterized by diffuse redness, persistent hyperhidrosis, and small dark red papules that disappear on diascopic pressure.

It is not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathyway, the prenylation chains (geranylgeraniol and farnesol) might play a role.

Brooke-Spiegler syndrome is a condition where multiple skin tumors develop from skin structures. Tumors commonly occurring in this syndrome include spiradenomas, trichoepitheliomas, and cylindromas. The tumors are generally benign, but may become malignant. Affected individuals are also at increased risk of developing tumors in tissues other than skin – particularly benign or malignant tumors of the salivary glands.

Tumours in Brooke-Spiegler typically appear in early adulthood and are most often found on the head and neck. In severe cases, the tumors may affect vision or hearing. They can be disfiguring and may contribute to depression or other psychological problems. For unclear reasons, females are often more severely affected than males.

Brooke-Spiegler is rare and its exact incidence is unknown.

It is inherited in an autosomal dominant fashion.

Acne treatment may require oral tetracycline antibiotics or isotretinoin. Treatments directed at tumor necrosis factor (TNF) (infliximab, etanercept) and interleukin-1 (anakinra) have shown a good response in resistant arthritis and pyoderma gangrenosum. Other traditional immunosuppressant treatments for arthritis or pyoderma gangrenosum may also be used.

Topical steroid preparations often help outbreaks; use of the weakest corticosteroid that is effective is recommended to help prevent thinning of the skin. Drugs such as antibiotics, antifungals, corticosteroids, dapsone, methotrexate, thalidomide, etretinate, cyclosporine and, most recently, intramuscular alefacept may control the disease but are ineffective for severe chronic or relapsing forms of the disease. Intracutaneous injections of botulinum toxin to inhibit perspiration may be of benefit. Maintaining a healthy weight, avoiding heat and friction of affected areas, and keeping the area clean and dry may help prevent flares.

Some have found relief in laser resurfacing that burns off the top layer of the epidermis, allowing healthy non-affected skin to regrow in its place.

Secondary bacterial, fungal and/or viral infections are common and may exacerbate an outbreak. Some people have found that outbreaks are triggered by certain foods, hormone cycles and stress.

In a few cases naltrexone appears to help.

The classification of this syndrome is difficult. Three conditions are known to be caused by mutations in the" CYLD" gene: Brooke-Spiegler syndrome, multiple familial trichoepithelioma, and familial cylindromatosis. Clinically, these are distinct, but appear to arise from mutations in the same gene.

Types include:

Familial dysalbuminemic hyperthyroxinemia is a type of hyperthyroxinemia associated with mutations in the human serum albumin gene.

The term was introduced in 1982.

After diagnosis, it is important for patients to be continually monitored. The most common treatment for PPNAD is bilateral laparoscopic adrenalectomy; the process by which both adrenal glands are removed by a small incision.

Patients who have received this treatment will be prescribed mineralocorticoid and glucocorticoid steroids as they are no longer being naturally produced.

This is a treatment which has been used and refined since 1984.