The histological and ultrastructural features of Ledderhose and Dupuytren's disease are the same, which supports the hypothesis that they have a common cause and pathogenesis. As with Dupuytren's disease, the root cause(s) of Ledderhose's disease are not yet understood. It has been noted that it is an inherited disease and of variable occurrence within families, i.e. the genes necessary for it may remain dormant for a generation or more and then surface in an individual, or be present in multiple individuals in the same generation with varying degree.

There are certain identified risk factors. The disease is more commonly associated with -

- A family history of the disease

- Higher incidence in males

- Palmar fibromatosis 10-65% of the time.

- Peyronie's disease

- Epilepsy patients

- Patients of diabetes mellitus

There is also a suspected, although unproven, link between incidence and alcoholism, smoking, liver diseases, thyroid problems, and stressful work involving the feet.

Some researchers suggest that HGF is transmitted as a Mendelian trait since both autosomal dominant and autosomal recessive transmission has been reported since the early 1970s. (SOURCE 1) In more recent scientific literature, there is evidence in which pedigree analyses confirm autosomal dominant, autosomal recessive or even as X-linked inherited cases of the HGF trait.

In 2002, researchers described the SOS1 gene and proved for the first time that a single-nucleotide–insertion mutation of the SOS1 gene on codon 1083 is the preliminary cause of HGF1 in humans. (Source 1) Later on in 2010, there was a case study done on a 16-year-old male with severe gingival overgrowth, almost covering all teeth. Researchers approached this issue with periodontics - a partial gingivectomy and flap surgery. This case study concluded that surgery followed by regular follow-ups is a good way to treat HGF despite the fact that the risks of re-occurrence of the condition remain high.

Even more recently, a study was done in 2013 on a family that showed history of autosomal recessive inheritance of HGF. The study did not dismiss the return of HGF after treatment but did claim that general surgical intervention after scaling and root planning of teeth supplemented with good oral hygiene is good enough to prevent the re-occurrence of HGF. This case study also acknowledged how HGF can be part of a multi-system syndrome associated with disorders such as Zimmermann Laband syndrome (ear, nose, bone, and nail defects with hepatosplenomegaly), Rutherford syndrome (microphthalmia, mental retardation, athetosis, and hypopigmentation), Murray-Puretic Drescher syndrome and Ramon syndrome.

HGF1 - Caused by a mutation in the SOS1 gene localized on chromosome 2p21-p22

HGF2 - Caused by a mutation in the SOS1 gene localized on chromosome 5q13-q22

Mutations in the RE1-silencing transcription factor (REST) gene can also cause this syndrome.

- Non genetic

HGF may also be caused by unwanted side effects of pharmacological agents like phenytoin, ciclosporin, and some calcium-channel blockers, meaning HGF is a disease that can be drug-induced. However, there is little next to no research done in this area to support the claim.

- Inflammation

- Hormonal Imbalance

- Neoplasia

- More commonly associated with an autosomal dominant gene inheritance

- Multi-system syndromes: Zimmerman-Laband syndrome, Jones syndrome, Ramon syndrome, Rutherford syndrome, juvenile hyaline fibromatosis, systemic infantile hyalinosis, and mannosidosis

- Some unknown causes

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

Focal palmoplantar and gingival keratosis is a rare autosomal dominant disease whose clinical features, and in particular, pathologic alterations and molecular mechanisms remains to be well defined.

There is no treatment, but because this is a benign condition with no serious clinical complications, prognosis is excellent.

White sponge nevus (WSN, or white sponge naevus, Cannon's disease, hereditary leukokeratosis of mucosa, white sponge nevus of Cannon, familial white folded dysplasia, or oral epithelial nevus), is an autosomal dominant condition of the oral mucosa (the mucous membrane lining of the mouth). It is caused by a mutations in certain genes coding for keratin, which causes a defect in the normal process of keratinization of the mucosa. This results in lesions which are thick, white and velvety on the inside of the cheeks within the mouth. Usually, these lesions are present from birth or develop during childhood. The condition is entirely harmless, and no treatment is required.

This condition occurs in association with denture wearing, and so those affected tend to be middle aged or older adults. 66-75% are estimated to occur in women. Epulis fissuratum is the third most common reactive lesion that occurs in the mouth, after peripheral giant cell granuloma and pyogenic granuloma.

Many systemic diseases can develop oral manifestations that may include gingival enlargement, some that are related to conditions and others that are related to disease:

- Conditioned enlargement

- pregnancy

- puberty

- vitamin C deficiency

- nonspecific, such as a pyogenic granuloma

- Systemic disease causing enlargement

- leukemia

- granulolomatous diseases, such as granulomatosis with polyangiitis, sarcoidosis, or orofacial granulomatosis.

- neoplasm

- benign neoplasms, such as fibromas, papillomas and giant cell granulomas

- malignant neoplasms, such as a carcinoma or malignant melanoma

- false gingival enlargements, such as when there is an underlying bony or dental tissue lesion

This type of gingival enlargement is sometimes termed "drug induced gingival enlargement" or "drug influenced gingival enlargement", abbreviated to "DIGO". Gingival enlargement may also be associated with the administration of three different classes of drugs, all producing a similar response: Gingival overgrowth is a common side effect of phenytoin, termed "Phenytoin-induced gingival overgrowth" (PIGO).

- anticonvulsants (such as phenytoin, phenobarbital, lamotrigine, vigabatrin, ethosuximide, topiramate and primidone NOT common for valproate)

- calcium channel blockers (antihypertensives such as nifedipine, amlodipine, and verapamil). The dihydropyridine derivative isradipidine can replace nifedipine and does not induce gingival overgrowth.

- cyclosporine, an immunosuppresant.

Of all cases of DIGO, about 50% are attributed to phenytoin, 30% to cyclosporins and the remaining 10-20% to calcium channel blockers.

Drug-induced enlargement has been associated with a patient's genetic predisposition, and its association with inflammation is debated. Some investigators assert that underlying inflammation is necessary for the development of drug-induced enlargement, while others purport that the existing enlargement induced by the drug effect compounds plaque retention, thus furthering the tissue response. Careful attention to oral hygiene may reduce the severity of gingival hyperplasia. In most cases, discontinuing the culprit drug resolves the hyperplasia.

OFG is uncommon, but the incidence is increasing. The disease usually presents in adolescence or young adulthood. It may occur in either sex, but males are slightly more commonly affected.

STK is extremely common among smokeless tobacco users. Given the association with smokeless tobacco use, this condition tends to occur in adults. A national USA survey estimated an overall prevalence of 1.5% of all types of smokeless tobacco lesions, with males affected more commonly than females.

Gingival fibroma is a cutaneous condition that may be observed with another condition, tuberous sclerosis.

Infantile myofibromatosis (also known as "Congenital generalized fibromatosis," and "Congenital multicentric fibromatosis") is the most common fibrous tumor of infancy, in which eighty percent of patients have solitary lesions with half of these occurring on the head and neck, and 60% are present at or soon after birth. Less commonly, infantile myofibromatosis presents as multiple lesions of skin, muscle, and bone with about 1/3 of these cases also having lesions in their visceral organs. All of these cases have an excellent prognosis with their tumors sometimes regressing spontaneously except for those cases in which there is visceral involvement where the prognosis is poor. Infantile myofibromatosis and the classic form of mesoblastic nephroma have been suggested to be the same disease because of their very similar histology. However, studies on the distribution of cell-type markers (i.e. cyclin D1 and Beta-catenin) indicate that the two neoplasms likely have different cellular origins.

Aggressive infantile fibromatosis is a locally recurring, non-metastasizing lesion, presenting with a single or multiple fast-growing masses that are present at birth or occur within the first year of life.

Juvenile hyaline fibromatosis (also known as "Fibromatosis hyalinica multiplex juvenilis," "Murray–Puretic–Drescher syndrome") is a very rare, autosomal recessive disease due to mutations in capillary morphogenesis protein-2 (CMG-2 gene). It occurs from early childhood to adulthood, and presents as slow-growing, pearly white or skin-colored dermal or subcutaneous papules or nodules on the face, scalp, and back, which may be confused clinically with neurofibromatosis.

Verruciform xanthoma is most likely not a human papillomavirus associated lesion and the foam cells in the lesions are most likely derived from the monocyte—macrophage lineage. More research is needed is determine the cause.

Treatment usually involves surgical removal of the lesion down to the bone. If there are any adjacent teeth, they are cleaned thoroughly to remove any possible source of irritation. Recurrence is around 16%.

If the causative factor persists, tissue will become more fibrous over time.

The peripheral odontogenic fibroma is an uncommon gingival mass. It affects people across a large age range. It can be confused with the peripheral ossifying fibroma. In contrast to the peripheral ossifying fibroma, the peripheral odontogenic fibroma is a rare lesion.

No specific gender predilection while the ages of the patients ranged from 5 to 65 years.commonly seen in mandible than maxilla.

slow growing, solid, firmly attached gingival mass sometimes arising between teeth and sometimes displacing teeth.

consists of cellular fibrous connective tissue parenchyma with non neoplastic islands, strands of clouman or cuboidal odontogenic epithelium.

Gingival fibromatosis with hypertrichosis is a cutaneous condition characterized by dark terminal hairs on the peripheral face, central back, and extremities. It is a RASopathy.

The term fibromatosis refers to a group of soft tissue tumors which have certain characteristics in common, including absence of cytologic and clinical malignant features, a histology consistent with proliferation of well-differentiated fibroblasts, an infiltrative growth pattern, and aggressive clinical behavior with frequent local recurrence. It is classed by the World Health Organisation as an intermediate soft tissue tumor related to the sarcoma family.

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.

Diffuse infantile fibromatosis is a condition affecting infants during the first 3 years of life. It is usually confined to the muscles of the arms, neck, and shoulder area. There is a multicentric infiltration of muscle fibers with fibroblasts resembling those seen in aponeurotic fibromas.

Epulis (; plural "epulides") is any tumor like enlargement (i.e. lump) situated on the gingival or alveolar mucosa. The word literally means "(growth) on the gingiva", and describes only the location of the mass and has no further implications on the nature of the lesion. There are three types: fibromatous, ossifying and acanthomatous. The related term parulis (commonly called a gumboil) refers to a mass of inflamed granulation tissue at the opening of a draining sinus on the alveolus over (or near to) the root of an infected tooth. Another closely related term is gingival enlargement, which tends to be used where the enlargement is more generalized over the whole gingiva rather than a localized mass.