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.

Infantile systemic hyalinosis or juvenile systemic hyalinosis is an allelic autosomal-recessive condition characterized by multiple skin nodules, hyaline deposition, gingival hypertrophy, osteolytic bone lesions, and joint contractures.

The RASopathies are developmental syndromes caused by germline mutations (or in rare cases by somatic mosaicism) in genes that alter the Ras subfamily and mitogen-activated protein kinases that control signal transduction, including:

- Capillary malformation-AV malformation syndrome

- Autoimmune lymphoproliferative syndrome

- Cardiofaciocutaneous syndrome

- Hereditary gingival fibromatosis type 1

- Neurofibromatosis type 1

- Noonan syndrome

- Costello syndrome, Noonan-like

- Legius syndrome, Noonan-like

- Noonan syndrome with multiple lentigines, formerly called LEOPARD syndrome, Noonan-like

Spitz nevi are uncommon. Their annual incidence was estimated in a coastal population of sub-tropical Queensland to be 1.4 cases per 100,000 people. For comparison, the annual incidence of melanoma in the same population, which is high by world standards is 25.4 cases per 100,000 people.

Although they are most commonly found on people in their first two decades of life, the age range for people with Spitz nevi is from 6 months to 71 years, with a mean age of 22 years and a median age of 19 years.

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.

Urbach–Wiethe disease is very rare; there are fewer than 300 reported cases in medical literature. Although Urbach–Wiethe disease can be found worldwide, almost a quarter of reported diagnoses are in South Africa. Many of these are in patients of Dutch, German, and Khoisan ancestry. This high frequency is thought to be due to the founder effect. Due to its recessive genetic cause and the ability to be a carrier of the disease without symptoms, Urbach–Wiethe disease often runs in families. In some regions of South Africa, up to one in 12 individuals may be carriers of the disease. Most of the case studies involving Urbach–Wiethe disease patients involve only one to three cases and these cases are often in the same family. Due to its low incidence, it is difficult to find a large enough number of cases to adequately study the disease.

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

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.

Infantile digital fibromatosis (also known as an "Inclusion body fibromatosis," "Infantile digital myofibroblastoma," and "Reye tumor") usually occurs as a small, asymptomatic, nodular, dermal fibrous proliferation at the extensor or lateral surface of a finger or toe.

This is a very rare phenomenon (50 years of age), and more commonly in women than men (5:1). There is an increased frequency in Okinawa, Japan, but this may be a reporting bias.

The tumor develops very specifically in the subscapular or infrascapular area, deep to the muscle, sometimes even attached to periosteum of ribs. It is usually between the shoulder blade and the lower neck, with rare tumors reported in the chest wall.

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.

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.

Urbach–Wiethe disease is typically not a life-threatening condition. The life expectancy of these patients is normal as long as the potential side effects of thickening mucosa, such as respiratory obstruction, are properly addressed. Although this may require a tracheostomy or carbon dioxide laser surgery, such steps can help ensure that individuals with Urbach–Wiethe disease are able to live a full life. Oral dimethyl sulfoxide (DMSO) has been shown to reduce skin lesions, helping to minimize discomfort for these individuals.

Subtypes of fibromatosis include -

- Juvenile fibromatosis

- Fibromatosis colli: Non-neoplastic sternocleidomastoid muscle enlargement in early infancy. Does not generally require resection and responds well to physiotherapy.

- Infantile digital fibromatosis

- Infantile myofibromatosis

- Ipofibromatosis

- Fibromatosis hyalinica multiplex

- Plantar fibromatosis

- Penile fibromatosis (Peyronie's disease)

- Palmar fibromatosis (Dupuytren's contracture)

A Spitz nevus (also known as an epithelioid and spindle-cell nevus, benign juvenile melanoma, and "Spitz's juvenile melanoma") is a benign melanocytic nevus, a type of skin lesion, affecting the epidermis and dermis.

The name "juvenile melanoma" is generally no longer used as it is misleading: it is not a melanoma, it is a benign lesion; and it can also occur in adults, not only in children.

Most juvenile polyps are benign, however, malignancy can occur. The cumulative lifetime risk of colorectal cancer is 39% in patients with juvenile polyposis syndrome.

There are several theories about origin:

- There is support for a genetic predisposition, as there are alterations of short arm of chromosome 1;

- Multifocality may suggest systemic enzymatic defect, resulting in abnormal elastogenesis;

- Repeated trauma or friction seems unlikely, but is still a possibility.

Self-healing papular mucinosis is a skin condition caused by fibroblasts producing abnormally large amounts of mucopolysaccharides, and may present in adult and juvenile forms. The juvenile variant is also called self-healing juvenile cutaneous mucinosis.

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.

Zimmermann–Laband syndrome (ZLS), also known as Laband–Zimmermann syndrome, and Laband's syndrome, is an extremely rare autosomal dominant congenital disorder.

Symptoms include gingival fibromatosis, associated with hypoplasia of the distal phalanges, nail dysplasia, joint hypermobility, and sometimes hepatosplenomegaly. The nose and pinnae are usually large and poorly developed, which gives the individuals with the syndrome abnormal facial characteristics. Mental retardation may also occur. Both males and females are equally affected. Gingival fibromatosis is usually present at birth or appears short after. The term Zimmermann–Laband was coined by Carl Jacob Witkop in 1971.

Fibrocartilaginous mesenchymoma of bone is (FCMB) is an extremely rare tumor first described in 1984. Fewer than 20 cases have been reported, with patient ages spanning from 9 to 25 years, though a case in a male infant aged 1 year and 7 months has been reported. Quick growth and bulky size are remarkable features of this tumor.

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.

Surgery is curative despite possible local relapses. Wide resection of the tumor and resection arthrodesis with an intramedullary nail, vertebrectomy and femoral head allograft replacement of the vertebral body, resection of the iliac wing and hip joint disarticulation have been among the performed procedures.

The close resemblance of FCMB to fibrocartilaginous dysplasia has suggested to some scholars that they might be closely related entities, although the latter features woven bone trabeculae without osteoblastic rimming, which is a quite distinctive aspect. Instead the occurrence of epiphyseal plate-like cartilage is peculiar of the former.

Both average parents

1.) A couple already has a child with chondrodystrophy; the risk of inheritance for the next child to have the disorder is 0.1% (less than 1 in 1,000)

2.) The risk that the normal-statured child will have at least one offspring with this disorder is 0.01% (less than 1 in 10,000)

One parent with chondrodystrophy and one parent without

1.) One child with normal height; the probability of that child having offspring with chondrodystrophy is 0.01% (less than 1 in 10,000)

2.) One child with normal stature; the probability of the next having chondrodystrophy is 50% (1 in 2)

3.) One child with normal stature; the probability of the next not having chondrodystrophy is 50% (1 in 2)

Both parents with chondrodystrophy

1.) The probability of offspring affected by chondrodystrophy is 100% (4 in 4)

2.) The probability of offspring to be of normal size is 0% (0 in 4)