What are the other Names for this Condition? (Also known as/Synonyms)

• JHF (Juvenile Hyaline Fibromatosis)
• Molluscum Fibrosum
• Murray-Puretic-Drescher Syndrome

What is Juvenile Hyaline Fibromatosis? (Definition/Background Information)

• Juvenile Hyaline Fibromatosis (JHF) is a highly infrequent genetic disorder affecting infant children, resulting in the formation of multiple subcutaneous nodules
• These nodules are formed by an abnormal accumulation of extracellular material affecting the muscles, bones, soft tissues, and the overlying skin. These benign tumors can disrupt the function of various body organs and even the joints
• The cause of Juvenile Hyaline Fibromatosis is due to gene mutations that disrupt the function of certain proteins in the body. Parents who are closely-related to each other (blood relatives) are at the highest risk for JHF
• The mainstay of treatment for Juvenile Hyaline Fibromatosis is surgical excision and tumor removal. However, deep-seated tumors that have affected the bones are difficult to access and/or remove
• The prognosis of Juvenile Hyaline Fibromatosis is dependent upon a set of factors including the numbers and sizes of the tumors, their locations in the body, and the extent of organ damage it has caused. The prognosis of JHF is generally difficult to predict and may be assessed on a case-by-case basis

Who gets Juvenile Hyaline Fibromatosis? (Age and Sex Distribution)

• Juvenile Hyaline Fibromatosis is an extremely rare congenital condition affecting newborns and infants. It is manifested at birth and is present throughout the child’s life
• Both male and female are affected by the condition with equal frequency
• No racial or ethnic group preference is noted

What are the Risk Factors for Juvenile Hyaline Fibromatosis? (Predisposing Factors)

The risk factors of Juvenile Hyaline Fibromatosis include:

• Individual with a positive family history of the condition
• Consanguineous union (or marriages among close blood-relations) greatly increases the risk for this autosomal recessive disorder
• JHF is seen to occur with infantile systemic hyalinosis (ISH), which is a rare genetic abnormality involving the formation of fibromatosis. Both conditions are known to have the same genetic origin

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Juvenile Hyaline Fibromatosis? (Etiology)

The exact cause of Juvenile Hyaline Fibromatosis development is unknown.

• It is a genetic disorder that is inherited in an autosomal recessive manner. Children with JHF often have parents who are closely blood-related
• Scientific research indicates that it develops due to ANTXR2 gene mutations that codes for a protein on chromosome 4
• This results in disruption of the basement membrane (thin layer separating the epithelium at various locations) leading to abnormal collection of hyaline material (a type of glassy material) at the affected regions/tissues
• This abnormal collection of these extracellular components results in the formation of benign tumors (single or multiple) beneath the cutaneous layers, giving rise to a set of associated signs and symptoms

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Juvenile Hyaline Fibromatosis?

The signs and symptoms of Juvenile Hyaline Fibromatosis include:

• The tumors may be single or numerous, form at different body locations, and grow at slow or rapid rates
• The presence of solid and firm nodules or papules, mostly on the head (face, near the ears) and neck region
• The nodules are known to destroy the tissue and body components where they form, due to the deposition of hyaline material into the soft tissues and organs of the body. The affected components may include:
  • The skin
  • Gums in the mouth, causing gingival hyperplasia
  • The soft tissues, particularly around the joints
  • The bones of the limbs, fingers, and skull
• Lesions around the anus may look like genital warts
• Deformity of the knee and elbow joints
• Osteoporosis of the affected bones, bone depletion
• Chronic infections and severe diarrhea may be noted in case the digestive tract is involved

How is Juvenile Hyaline Fibromatosis Diagnosed?

The following methods are adopted to diagnose Juvenile Hyaline Fibromatosis:

• A thorough physical examination and a complete medical history
• X-ray of the affected region
• CT scans and MRI scans of the affected region to assess the extent of tumor growth and destruction of surrounding tissues, muscles, and bones
• Tissue biopsy: In this procedure, the physician removes a sample of the accessible tissue and sends it to the laboratory for a histopathological examination. The pathologist examines the biopsy under a microscope and arrives at a definitive diagnosis after a thorough evaluation of the clinical and microscopic findings, as well as by correlating the results of special studies on tissues (if required)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Juvenile Hyaline Fibromatosis?

The complications of Juvenile Hyaline Fibromatosis may include the following:

• The major complication of JHF is that increased numbers and large sizes of subcutaneous and deep-seated tumors can lead to the destruction of organs and cause physical deformities. It can lead to severe functional impairment of the organs
• Deep tissue tumors and the involvement of the underlying bones can make surgical excision and tumor removal very difficult to undertake
• Recurrence of the tumor after surgical excision is observed in a majority of cases

How is Juvenile Hyaline Fibromatosis Treated?

The following treatment measures are adopted to treat Juvenile Hyaline Fibromatosis:

• The treatment of the tumor is by surgical excision. Complete excision and tumor removal should be performed, if possible, based on location accessibility. This can decrease the chance of tumor recurrence
• Undertaking appropriate treatment of other signs and symptoms
• Long-term follow-up with healthcare visits and multiple surgeries may be necessary

How can Juvenile Hyaline Fibromatosis be Prevented?

Currently, there are no specific methods or guidelines to prevent Juvenile Hyaline Fibromatosis since it is a genetic condition.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Juvenile Hyaline Fibromatosis

What is the Prognosis of Juvenile Hyaline Fibromatosis? (Outcomes/Resolutions)

• Juvenile Hyaline Fibromatosis is a genetic disorder and the prognosis of the condition is dictated by the number of tumors present, their locations, the degree of organ destruction, functional impairment, and overall health status of the individual
• The lesser the number of tumors, the more accessible their location for surgery, and the milder the signs and symptoms, the better is the overall prognosis. Many children are known to survive into adulthood

Additional and Relevant Useful Information for Juvenile Hyaline Fibromatosis:

Juvenile Hyaline Fibromatosis and infantile systemic hyalinosis are both caused by similar set of genetic mutations. Previously, the two conditions were considered as being distinct and separate, but now they are thought to be closely-related and belonging to the same genetic family.