This disease is more common in women and an association with the gene FLT4 has been described. FLT4 codes for VEGFR-3, which is implicated in development of the lymphatic system.

Milroy's disease is also known as primary or hereditary lymphedema type 1A or early onset lymphedema.

It is a very rare disease with only about 200 cases reported in the medical literature. Milroy's disease is an autosomal dominant condition caused by a mutation in the FLT4 gene which encodes of the vascular endothelial growth factor receptor 3 (VEGFR-3) gene located on the long arm (q) on chromosome 5 (5q35.3).

In contrast to Milroy's disease (early onset lymphedema type 1A,) which typically has its onset of swelling and edema at birth or during early infancy, hereditary lymphedema type II, known as Meige disease, has its onset around the time of puberty. Meige disease is also an autosomal dominant disease. It has been linked to a mutations in the ‘forkhead’ family transcription factor (FOXC2) gene located on the long arm of chromosome 16 (16q24.3). About 2000 cases have been identified. A third type of hereditary lymphedema, that has an onset after the age of 35 is known as lymph-edema tarda.

Meige lymphedema, also known as Meige disease, Late-onset lymphedema, and Lymphedema hereditary type 2, is an inherited disease in which patients develop lymphedema. The onset is between the ages of 1 and 35. Other causes of primary lympoedema include Milroy's disease which occurs before the age of 1, and lymphoedema tarda which occurs after the age of 35.

Meige disease,(Hereditary lymphedema type II), has its onset around the time of puberty. It is an autosomal dominant disease. It has been linked to a mutations in the ‘forkhead’ family transcription factor (FOXC2) gene located on the long arm of chromosome 16 (16q24.3). It is the most common form of primary lymphedema, and about 2000 cases have been identified. Meige disease usually causes lymphedema of the legs, however, other areas of the body may be affected, including the arms, face and larynx. Yellow toe nails occur in some individuals.

Milroy's disease (MD) is a familial disease characterized by lymphedema, commonly in the legs, caused by congenital abnormalities in the lymphatic system. Disruption of the normal drainage of lymph leads to fluid accumulation and hypertrophy of soft tissues. It is also known as Milroy disease, Nonne-Milroy-Meige syndrome and hereditary lymphedema.

It was named by Sir William Osler for William Milroy, a Canadian physician, who described a case in 1892, though it was first described by Rudolf Virchow in 1863.

The Aagenæs syndrome or Aagenaes syndrome is a syndrome characterised by congenital hypoplasia of lymph vessels, which causes lymphedema of the legs and recurrent cholestasis in infancy, and slow progress to hepatic cirrhosis and giant cell hepatitis with fibrosis of the portal tracts.

The genetic cause is unknown, but it is autosomal recessively inherited and the gene is located to chromosome 15q. A common feature of the condition is a generalised lymphatic anomaly, which may be indicative of the defect being lymphangiogenetic in origin. The condition is particularly frequent in southern Norway, where more than half the cases are reported from, but is found in patients in other parts of Europe and the United States. It is named after Øystein Aagenæs, a Norwegian paediatrician.

It is also called cholestasis-lymphedema syndrome (CLS).

Primary lymphedema is a form of lymphedema which is not directly attributable to another medical condition.

It can be divided into three forms, depending upon age of onset: congenital lymphedema, lymphedema praecox, and lymphedema tarda.

Congenital lymphedema presents at birth. Lymphedema praecox presents from ages 1 to 35. This type of lymphedema accounts for 77–94% of all cases of primary lymphedema. Lymphedema tarda presents after age 35. This type of lymphedema usually develops as a result of a developmental abnormality being precipitated by some insult such as trauma, illness, or physical immobility. Compared to secondary lymphedema, primary lymphedema is more likely to involve the face, conjunctiva, and genitalia in association with any limbs involved.

It can be familial.

People with yellow nail syndrome have been found to have a moderately reduced lifespan compared to people without the condition.

Although it has been described in families, it has been suggested that it might not have a genetic link.

In the 1960s, the incidence 5 years after a radical mastectomy varied from 0.07% to 0.45%.

Today, it occurs in 0.03% of patients surviving 10 or more years after radical mastectomy.

Verruciform xanthoma is uncommon, with a female:male ratio of 1:1.1

Hypotrichosis–lymphedema–telangiectasia syndrome is a congenital syndrome characterized by lymphedema (swelling of tissue due to malformation or malfunction of lymphatics), the presence of telegiectasias (small dilated vessels near the surface of the skin), and hypotrichosis or alopecia (hair loss). Lymphedema usually develops in the lower extremities during puberty. Hair is normal at birth, but usually lost during infancy. Telangiectasias may present on the palms and soles more commonly than on the scalp, legs, and genitalia. The syndrome has been reported in association with both autosomal dominant and autosomal recessive inheritance patterns.

It is associated with a rare mutation of the transcription factor gene "SOX18".

Early detection is key. Untreated patients usually live 5 to 8 months after diagnosis.

Ring chromosome 14 syndrome is extremely rare, the true rate of occurrence is unknown (as it is "less than" 1 per 1,000,000), but there are at least 50 documented cases in the literature.

Lymphedema praecox is a condition characterized by swelling of the soft tissues in which an excessive amount of lymph has accumulated, and generally develops in females between the ages of nine and twenty-five.This is the most common form of primary lymphedema, accounting for about 80% of the patients.

Lymphedema–distichiasis syndrome is a medical condition associated with the FOXC2 gene.

When the lymphatic impairment becomes so great that the lymph fluid exceeds the lymphatic system's ability to transport it, an abnormal amount of protein-rich fluid collects in the tissues. Left untreated, this stagnant, protein-rich fluid causes tissue channels to increase in size and number, reducing oxygen availability. This interferes with wound healing and provides a rich culture medium for bacterial growth that can result in infections: cellulitis, lymphangitis, lymphadenitis and in severe cases, skin ulcers. It is vital for lymphedema patients to be aware of the symptoms of infection and to seek immediate treatment, since recurrent infections or cellulitis, in addition to their inherent danger, further damage the lymphatic system and set up a vicious circle.

In rare cases, lymphedema can lead to a form of cancer called lymphangiosarcoma, although the mechanism of carcinogenesis is not understood. Lymphedema-associated lymphangiosarcoma is called Stewart-Treves syndrome. Lymphangiosarcoma most frequently occurs in cases of long-standing lymphedema. The incidence of angiosarcoma is estimated to be 0.45% in patients living 5 years after radical mastectomy. Lymphedema is also associated with a low grade form of cancer called retiform hemangioendothelioma (a low grade angiosarcoma).

Since lymphedema is disfiguring, causing difficulties in daily living and can lead to lifestyle becoming severely limited, it may also result in psychological distress.

Hennekam syndrome also known as intestinal lymphagiectasia–lymphedema–mental retardation syndrome, is an autosomal recessive disorder consisting of intestinal lymphangiectasia, facial anomalies, peripheral lymphedema, and mild to moderate levels of growth and intellectual disability.

It is also known as "lymphedema-lymphangiectasia-mental retardation syndrome".

In a subset of patients it is associated with CCBE1 according research published by its namesake, Raoul Hennekam. Other causal mutations were found in the FAT4 gene. Previously, mutations in the FAT4 gene had been only associated with van Maldergem syndrome. The molecular mechanism of the lymphedema phenotype in CCBE1-associated cases was identified as a diminished ability of the mutated CCBE1 to accelerate and focus the activation of the primary lymphangiogenic growth factor VEGF-C.

HSAN I constitutes a clinically and genetically heterogeneous group of diseases of low prevalence. Detailed epidemiological data are currently not available. The frequency of the disease is still reflected by reports of a handful affected families. Although the impressive clinical features of HSAN I are seen by neurologists, general practitioners, orthopedists, and dermatologists, the condition might still be under-recognized particularly for sporadic cases and patients who do not exhibit the characteristic clinical features.

Lymphedema affects approximately 140 million people worldwide.

Lymphedema may be inherited (primary) or caused by injury to the lymphatic vessels (secondary). It is most frequently seen after lymph node dissection, surgery and/or radiation therapy, in which damage to the lymphatic system is caused during the treatment of cancer, most notably breast cancer. In many patients with cancer, this condition does not develop until months or even years after therapy has concluded. Lymphedema may also be associated with accidents or certain diseases or problems that may inhibit the lymphatic system from functioning properly. In tropical areas of the world, a common cause of secondary lymphedema is filariasis, a parasitic infection. It can also be caused by a compromising of the lymphatic system resulting from cellulitis.

While the exact cause of primary lymphedema is still unknown, it generally occurs due to poorly developed or missing lymph nodes and/or channels in the body. Lymphedema may be present at birth, develop at the onset of puberty (praecox), or not become apparent for many years into adulthood (tarda). In men, lower-limb primary lymphedema is most common, occurring in one or both legs. Some cases of lymphedema may be associated with other vascular abnormalities.

Secondary lymphedema affects both men and women. In women, it is most prevalent in the upper limbs after breast cancer surgery, in particular after axillary lymph node dissection, occurring in the arm on the side of the body in which the surgery is performed. Breast and trunk lymphedema can also occur but, go unrecognised as there is swelling in the area after surgery and its symptoms ( peau d' orange and/or an inverted nipple ) can be confused with post surgery fat necrosis. In Western countries, secondary lymphedema is most commonly due to cancer treatment. Between 38 and 89% of breast cancer patients suffer from lymphedema due to axillary lymph node dissection and/or radiation. Unilateral lymphedema occurs in up to 41% of patients after gynecologic cancer. For men, a 5-66% incidence of lymphedema has been reported in patients treated with incidence depending on whether staging or radical removal of lymph glands was done in addition to radiotherapy.

Head and neck lymphedema can be caused by surgery or radiation therapy for tongue or throat cancer. It may also occur in the lower limbs or groin after surgery for colon, ovarian or uterine cancer, in which removal of lymph nodes or radiation therapy is required. Surgery or treatment for prostate, colon and testicular cancers may result in secondary lymphedema, particularly when lymph nodes have been removed or damaged.

The onset of secondary lymphedema in patients who have had cancer surgery has also been linked to aircraft flight (likely due to decreased cabin pressure or relative immobility). For cancer survivors, therefore, wearing a prescribed and properly fitted compression garment may help decrease swelling during air travel.

Some cases of lower-limb lymphedema have been associated with the use of tamoxifen, due to the blood clots and deep vein thrombosis (DVT) that can be caused by this medication. Resolution of the blood clots or DVT is needed before lymphedema treatment can be initiated.

Affected breeds include the Shire, Clydesdale, Belgian, Gypsy cob, and Friesian. Signs are usually only seen in horses older than two years. Both sexes are affected.

Acquired telangiectasia, not related to other venous abnormalities, for example on the face and trunk, can be caused by factors such as

- Acne rosacea

- Blepharitis

- Environmental damage such as that caused by sun or cold exposure

- Age

- Trauma to skin such as contusions or surgical incisions.

- Radiation exposure such as that experienced during radiotherapy for the treatment of cancer

- Chemotherapy

- Carcinoid syndrome

- Limited systemic sclerosis/scleroderma (a Scleroderma sub-type)

- Chronic treatment with topical corticosteroids may lead to telangiectasia.

- Spider angiomas are a radial array of tiny arterioles that commonly occur in pregnant women and in patients with hepatic cirrhosis and are associated with palmar erythema. In men, they are related to high estrogen levels secondary to liver disease.

- Tempi syndrome

- Smoking

Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment. The skin weighs an average of four kilograms, covers an area of two square meters, and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are: glabrous skin, the hairless skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, the hairs occur in structures called pilosebaceous units, each with hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands form from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues.

The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers by diffusion from the dermis, since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95 percent of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum.

The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing.

The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source.

Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on. Clinically, the diagnosis of any particular skin condition is made by gathering pertinent information regarding the presenting skin lesion(s), including the location (such as arms, head, legs), symptoms (pruritus, pain), duration (acute or chronic), arrangement (solitary, generalized, annular, linear), morphology (macules, papules, vesicles), and color (red, blue, brown, black, white, yellow). Diagnosis of many conditions often also requires a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data.

In the past, people used to think that leg varicose veins or telangectasia were caused by high venous pressure or "venous hypertension". However it is now understood that venous reflux disease is usually the cause of these problems (see above for reference for "venous reflux".

Telangiectasia in the legs is often related to the presence of venous reflux within underlying varicose veins. Flow abnormalities within the medium-sized veins of the leg (reticular veins) can also lead to the development of telangiectasia.

Factors that predispose to the development of varicose and telangiectatic leg veins include

- Age: The development of spider veins may occur at any age but usually occurs between 18 and 35 years, and peaks between 50 and 60 years.

- Gender: It used to be thought that females were affected far more than males. However research has shown 79% of adult males and 88% of adult females have leg telangectasia (spider veins).

- Pregnancy: Pregnancy is a key factor contributing to the formation of varicose and spider veins. The most important factor is circulating hormones that weaken vein walls. There's also a significant increase in the blood volume during pregnancy, which tends to distend veins, causing valve dysfunction which leads to blood pooling in the veins. Moreover, later in pregnancy, the enlarged uterus can compress veins, causing higher vein pressure leading to dilated veins. Varicose veins that form during pregnancy may spontaneously improve or even disappear a few months after delivery.

- Lifestyle/occupation: Those who are involved with "prolonged sitting or standing" in their daily activities have an increased risk of developing varicose veins. The weight of the blood continuously pressing against the closed valves causes them to fail, leading to vein distention.

Treatment consists of antibiotics, elevation of the affected limb, and compression. For persons with elephantiasis nostras who are overweight or obese, weight loss is recommended. Oral retinoids have been used to treat the cutaneous manifestations of the disease.

Verruciform xanthoma is an uncommon benign lesion that has a verruciform (wart-like) appearance, but it may appear polypoid, papillomatous, or sessile. The verruciform was first described by Shafer in 1971 on the oral mucosa. Usually found on the oral mucosa of middle-aged persons, verruciform xanthomas have also been reported on the scrotum and penis of middle-aged to elderly Japanese males. While the most common site is the oral mucosa, lesions that occur elsewhere usually arise on the perineum or on the skin with some predisposing factor, such as lymphedema or an epidermal nevus.

Genetic counseling is an important tool for preventing new cases if this is wished by at-risk family members. Appropriate genetic counseling is based on an accurate diagnosis. Therefore, clinicians and genetic counselors should use ulcero-mutilating complications as the main diagnostic criteria. Since the disease is inherited as an autosomal dominant trait, there is a Mendelian risk of 50% for subsequent generations regardless of their sex. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation has been identified in the family. Predictive testing is useful for young people to avoid serious complications of the disease.