Vulvar Paget disease presents as a variety of clinical lesions that may occur over a protracted course. Initially it is velvety, soft, and red or bright pink with scattered white islands of hyperkeratosis. (a strawberry and cream appearance) The lesions become erythematous, plaque like, and desquamating especially when located in dry areas. Rarely the appearance is ulcerated. The borders appear irregular, slightly elevated, and sharply demarcated. The visible borders of vulvar Paget disease are often misleading as Paget cells may spread along the basal layers of normal appearing skin with multicentric foci. Involvement may be extensive including the perianal region, genitocrural, and inguinal folds. Clinical examination should determine the presence of periurethral and perianal lesions. In these cases an involvement of the skin by a noncutaneous internal neoplasm may occur.

Symptoms are not specific; most patients report itching, burning, and soreness. A small subset of patients may be asymptomatic. Presence of vulvar pain, bleeding, and tumor formation are reported to be more common in patients affected by invasive disease.Signs and symptoms are skin lesions, often mistaken as eczema, that may be itchy or painful.

Galli–Galli disease is a rare inherited condition that has close resemblance clinically to Dowling-Degos' disease, but is histologically distinct, characterized by skin lesions that are 1- to 2-mm slightly keratotic red to dark brown papules which are focally confluent in a reticulate pattern. The disease is also characterized by slowly progressive and disfiguring reticulate hyperpigmentation of the flexures, clinically and histopathologically diagnostic for Dowling-Degos disease but also associated with suprabasal, nondyskeratotic acantholysis.

The symptoms of ichthyosis hystrix Curth-Macklin are similar to epidermolytic hyperkeratosis (NPS-2 type) but there is no blistering and the hyperkeratosis is verrucous or spine-like. The hyperkeratosis is brown-grey in colour and is most obvious on the arms and legs. It is an autosomal dominant condition and can be caused by errors to the KRT1 gene. It is named after Helen Ollendorff Curth (1899-1982), a German-Jewish dermatologist, and Madge Thurlow Macklin (1893–1962), an American medical geneticist, and is one of the first syndromes named after two women.

Ichthyosis hystrix is a group of rare skin disorders in the ichthyosis family of skin disorders characterized by massive hyperkeratosis with an appearance like spiny scales. This term is also used to refer to a type of epidermal nevi with extensive bilateral distribution.

Long bone involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 50% of cases have some sort of extraskeletal involvement. This can include kidney, skin, brain and lung involvement, and less frequently retroorbital tissue, pituitary gland and heart involvement is observed.

Bone pain is the most frequent of all symptoms associated with ECD and mainly affects the lower limbs, knees and ankles. The pain is often described as mild but permanent, and in nature. Exophthalmos occurs in some patients and is usually bilateral, symmetric and painless, and in most cases it occurs several years before the final diagnosis. Recurrent pericardial effusion can be a manifestation, as can morphological changes in adrenal size and infiltration.

A review of 59 case studies by Veyssier-Belot, C et al. in 1996 reported the following symptoms in order of frequency of occurrence:

- Bone pain

- Retroperitoneal fibrosis

- Diabetes insipidus

- Exophthalmos

- Xanthomas

- Neurological signs ("including Ataxia")

- Dyspnea caused by interlobular septal and pleural thickening.

- Kidney failure

- Hypopituitarism

- Liver failure

It is a genetic developmental disorder with clinical diversity characterized by hypoparathyroidism, sensorineural deafness and renal disease. Patients usually present with hypocalcaemia, tetany, or afebrile convulsions at any age. Hearing loss is usually bilateral and may range from mild to profound impairment. Renal disease includes nephrotic syndrome, cystic kidney, renal dysplasia, hypoplasia or aplasia, pelvicalyceal deformity, vesicoureteral reflux, chronic kidney disease, hematuria, proteinuria and renal scarring.

Lyngstadaas Syndrome, also known as severe dental aberrations in familial steroid dehydrogenase deficiency , is a rare autosomal recessive liver disease involving an enzyme (steroid dehydrogenase) deficiency and dental anomalies. The disease is named after the Norwegian professor Ståle Petter Lyngstadaas.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that MOPD, or a subtype of MOPD, affects less than 200,000 people in the US population and a form of dwarfism associated with brain and skeletal abnormalities.

It was characterized in 1982.

It is associated with "PCNT".

The disease causes numerous whitish punctiform papules and brownish macules arranged in a necklace-like pattern.

LCH provokes a non-specific inflammatory response, which includes fever, lethargy, and weight loss. Organ involvement can also cause more specific symptoms.

- Bone: The most-frequently seen symptom in both unifocal and multifocal disease is painful bone swelling. The skull is most frequently affected, followed by the long bones of the upper extremities and flat bones. Infiltration in hands and feet is unusual. Osteolytic lesions can lead to pathological fractures.

- Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules pronounced in intertriginous areas. Up to 80% of LCH patients have extensive eruptions on the scalp.

- Bone marrow: Pancytopenia with superadded infection usually implies a poor prognosis. Anemia can be due to a number of factors and does not necessarily imply bone marrow infiltration.

- Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases.

- Endocrine glands: Hypothalamic pituitary axis commonly involved. Diabetes insipidus is most common. Anterior pituitary hormone deficiency is usually permanent.

- Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others suffer from chronic cough and shortness of breath.

- Less frequently gastrointestinal tract, central nervous system, and oral cavity.

Lichen ruber moniliformis is a rare skin disease named for Fred Wise and Charles R. Rein.

It is one of several diseases also known as Kaposi's disease, based on its characterization in 1886 by Moritz Kaposi.

It is thought to be a rare variety of lichen planus.It is also known as "Morbus moniliformis lichenoides".

Office of Rare Diseases listed Lyngstadaas syndrome as a "rare disease". This means that Lyngstadaas syndrome, or a subtype of Lyngstadaas syndrome, affects less than 200,000 people in the US population.

Orphanet, a consortium of European partners, currently defines a condition rare when if affects 1 person per 2,000. They list Lyngstadaas syndrome as a "rare disease".

The symptoms of Gorham's disease vary depending on the bones involved. It may affect any part of the skeleton, but the most common sites of disease are the shoulder, skull, pelvic girdle, jaw, ribs, and spine.

In some cases there are no symptoms until a fracture occurs either spontaneously or following minor trauma, such as a fall. There may be an acute onset of localized pain and swelling. More commonly there is pain of no apparent cause that increases in frequency and intensity over time and may eventually be accompanied by weakness and noticeable deformity of the area. The rate of progression is unpredictable and the prognosis can be difficult. The disease may stabilize after a number of years, go into spontaneous remission, or, in cases involving the chest and upper spine, prove fatal. Recurrence of the disease following remission can also occur. Involvement of the spine and skull base may cause a poor outcome from neurological complications. In many cases, the end result of Gorham's disease is severe deformity and functional disability.

Symptoms such as difficulty breathing and chest pain may be present if the disease is present in the ribs, scapula, or thoracic vertebrae. These may indicate that the disease has spread from the bone into the chest cavity. The breathing problems may be misdiagnosed as asthma, because the damage done to the lungs can cause the same types of changes to lung function testing that are seen in asthma. Extension of the lesions into the chest may lead to the development of chylous pleural and pericardial effusions. Chyle is rich in protein and white blood cells that are important in fighting infection. The loss of chyle into the chest can have serious consequences, including infection, malnutrition, and respiratory distress and failure. These complications or their symptoms, such as difficulty breathing, chest pain, poor growth or weight loss, and infection have sometimes been the first indications of the condition.

Leontiasis ossea, also known as leontiasis, lion face or Lion Face Syndrome, is a rare medical condition, characterized by an overgrowth of the facial and cranial bones. It is not a disease in itself, but a symptom of other diseases, including Paget's disease, fibrous dysplasia, hyperparathyroidism and renal osteodystrophy.

The common form is that in which one or other maxilla is affected, its size progressively increasing, and thus encroaching on the cavities of the orbit, the mouth, the nose and its accessory sinuses. Exophthalmos gradually develops, going on later to a complete loss of sight due to compression of the optic nerve by the overgrowth of bone. There may also be interference with the nasal respiration and with the taking of food. In the somewhat less common form of this rare disease the overgrowth of bone affects all the cranial bones as well as those of the face, the senses being lost one by one and death finally resulting from cerebral pressure. There is no treatment other than exposing the overgrown bone, and chipping away pieces, or excising entirely where possible.

Erdheim–Chester disease (also known as Erdheim–Chester syndrome or polyostotic sclerosing histiocytosis) is a rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages (technically, this disease is termed a non-Langerhans-cell histiocytosis). Onset typically is in middle age. The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.

Ho–Kaufman–Mcalister syndrome, also known as the Chen-Kung Ho–Kaufman–Mcalister syndrome, is a rare congenital malformation syndrome where infants are born with a cleft palate, micrognathia, Wormian bones, congenital heart disease, dislocated hips, bowed fibulae, preaxial polydactyly of the feet, abnormal skin patterns, and most prominently, missing tibia. The etiology is unknown. Ho–Kaufman–Mcalister syndrome is named after Chen-Kung Ho, R.L. Kaufman, and W.H. Mcalister who first described the syndrome in 1975 at Washington University in St. Louis. It is considered a rare disease by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH).

Barakat syndrome, is a rare disease characterized by hypoparathyroidism, sensorineural deafness and renal disease, and hence also known as HDR syndrome. It was first described by Amin J. Barakat et al. in 1977.

Signs and symptoms of the disease include diarrhea, nausea, swelling of the legs, protein-losing enteropathy, immunodeficiency and loss of lymphatic fluid into the intestines. It is usually diagnosed before the patient is 3 years old, but it is sometimes diagnosed in adults.

Seen mostly in children, multifocal unisystem LCH is characterized by fever, bone lesions and diffuse eruptions, usually on the scalp and in the ear canals. 50% of cases involve the pituitary stalk, leading to diabetes insipidus. The triad of diabetes insipidus, exopthalmos, and lytic bone lesions is known as the "Hand-Schüller-Christian triad". Peak onset is 2–10 years of age.

Lhermitte–Duclos disease (LDD) (), also called dysplastic gangliocytoma of the cerebellum, is a rare, slowly growing tumor of the cerebellum, a gangliocytoma sometimes considered to be a hamartoma, characterized by diffuse hypertrophy of the granular layer of the cerebellum. It is often associated with Cowden syndrome. It was described by Jacques Jean Lhermitte and P. Duclos in 1920.

Zeichi-Ceide syndrome is a rare disease discovered in 2007. It is named after its discoverer, R.M. Zeichi-Ceide, who observed three siblings born of consanguineous parents with distinctive characteristics, including facial anomalies, large feet, mental deficiency, and occipital atretic cephalocele. The investigators suspected the symptoms were caused by autosomal recessive inheritance.

As a rare disease, Zeichi-Ceide syndrome is registered in the Online Mendelian Inheritance in Man and the U.S. National Institutes of Health's Genetic and Rare Diseases databases.

Surgeon Hutan Ashrafian from Imperial College London has analysed the Great Sphinx to identify that it may have represented an individual suffering from prognathism which may have been a reflection of a disease suffered by the sculpture’s human inspiration. Furthermore as the Sphinx represented a lion, the same person may have suffered from leontiasis ossea.

Waldmann disease, also known as Waldmann's disease and primary intestinal lymphangiectasia, is a rare disease characterized by enlargement of the lymph vessels supplying the lamina propria of the small intestine.

Although its prevalence is unknown, it being classified as a "rare disease" means that less than 200,000 of the population of the United States are affected by this condition and its subtypes.

In 1983 Heffez and colleagues published a case report in which they suggested eight criteria for a definitive diagnosis of Gorham's disease:

- Positive biopsy with the presence of angiomatous tissue

- Absence of cellular atypia

- Minimal or no osteoblastic response or dystrophic calcifications

- Evidence of local bone progressive osseous resorption

- Non-expansile, non-ulcerative lesions

- No involvement of viscera

- Osteolytic radiographic pattern

- Negative hereditary, metabolic, neoplastic, immunologic, or infectious etiology.

In the early stages of the disease x-rays reveal changes resembling patchy osteoporosis. As the disease progresses bone deformity occurs with further loss of bone mass and, in the tubular bones (the long bones of the arms and legs), a concentric shrinkage is often seen which has been described as having a "sucked candy" appearance. Once the cortex (the outer shell) of the bone has been disrupted, vascular channels may invade adjacent soft tissues and joints. Eventually, complete or near-complete resorption of the bone occurs and may extend to adjacent bones, though spontaneous arrest of bone loss has been reported on occasion. Throughout this process, as the bone is destroyed it is replaced by angiomatous and/or fibrous tissue.

Often Gorham's disease is not recognized until a fracture occurs, with subsequent improper bone healing. The diagnosis essentially is one of exclusion and must be based on combined clinical, radiological, and histopathological findings. X-rays, CT scans, MRIs, ultrasounds, and nuclear medicine (bone scans) are all important tools in the diagnostic workup and surgical planning, but none have the ability alone to produce a definitive diagnosis. Surgical biopsy with histological identification of the vascular or lymphatic proliferation within a generous section of the affected bone is an essential component in the diagnostic process.

Recognition of the disease requires a high index of suspicion and an extensive workup. Because of its serious morbidity, Gorham's must always be considered in the differential diagnosis of osteolytic lesions.