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Congenital Generalized Fibromatosis (CGF)

Congenital Generalized Fibromatosis (CGF) is a rare condition affecting infants or young children.

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

  • CGF (Congenital Generalized Fibromatosis)
  • Congenital Multiple Fibromatosis
  • Multicentric Infantile Myofibromatosis

What is Congenital Generalized Fibromatosis? (Definition/Background Information)

  • Congenital Generalized Fibromatosis (CGF) is a rare condition affecting infants or young children. It is characterized by a spontaneous formation of single or multiple tumors (mostly benign) all over the body. It is also known as Infantile Myofibromatosis
  • The condition may occur sporadically or can be inherited. In the rarer inherited form of the condition, a family history of Congenital Generalized Fibromatosis is the major risk factor. In cases where CGF is inherited, mutations in PDGFRB and NOTCH3 genes have been identified to be causative
  • The symptoms of Congenital Generalized Fibromatosis include the presence of tumors, which could be solitary or multiple. The tumors may be present on the skin, muscle, bones, or in the internal organs (such as the stomach, lungs, or heart)
  • A healthcare professional may employ a thorough physical examination, assess the presenting symptoms, evaluate one’s family medical history, and request tests, such as imaging and biopsy of the affected area, to aid in Congenital Generalized Fibromatosis diagnosis. A molecular genetic testing may be needed to confirm the diagnosis
  • In some cases, a spontaneous resolution of the condition can occur and the tumors may disappear completely. In other cases, surgical, radiological, or chemotherapeutic treatment may be needed. The treatment options for Congenital Generalized Fibromatosis depend on the number of tumors, their sizes, and locations
  • The prognosis is determined by factors, such as the size, location, and complexity of the tumors. Generally, children with superficial tumors (tumors on or just below the skin) have better outcomes than those with internal tumors that affect vital organs

Who gets Congenital Generalized Fibromatosis? (Age and Sex Distribution)

  • Congenital Generalized Fibromatosis affects neonates and young children (up to 2 years old). It is infrequently observed in older children and adults
  • The condition is rare, with an incidence rate of 1:150,000 to 1:400,000 among children. However, it is possible that the condition may be underdiagnosed or misdiagnosed, making it difficult to determine its exact prevalence
  • Although rare, it is reported to be the leading cause of fibrous tumors in young children
  • There is no racial, ethnic group, or gender bias known for the occurrence of CGF

What are the Risk Factors for Congenital Generalized Fibromatosis? (Predisposing Factors)

  • Currently, there are no known risk factors associated with Congenital Generalized Fibromatosis in cases where the condition occurs sporadically
  • A family history of the disorder is a major risk factor for inherited forms of CGF

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 Congenital Generalized Fibromatosis? (Etiology)

Congenital Generalized Fibromatosis is caused by spontaneous mutations in a majority of cases. The condition may occur due to mutation(s) in the following genes, when it is inherited:

  • PDGFRB gene:
    • PDGFRB stands for ‘platelet-derived growth factor receptor beta’. This gene codes for the PDGFRβ protein, a member of receptor tyrosine kinases family. PDGFRβ is involved in stimulation of key signaling pathways for growth, division, movement and viability of the cells
    • When there is a mutation in the gene, the resultant protein is abnormal in quantity and function. This leads to aberrant signaling in the pathways of cellular growth and division, leading to the disorder
    • The PDGFRB mutation is inherited in an autosomal dominant manner. In this type of inheritance, a single copy of the defective gene (in all the cells of the body), inherited from an affected parent, is sufficient to cause the condition
  • NOTCH3 gene:
    • This gene codes for the NOTCH3 protein. Normally, this protein localizes on the cell membrane, with portions of it on the outside and inside of the cell. The binding of factors to the extra-cellular part leads to detachment of the intra-cellular part, in order for it to influence cellular processes
    • Mutations in this gene are believed to cause the condition. However, only one family with CGF has been reported to have this mutation
    • NOTCH3 mutation resulting in CGF is inherited in an autosomal recessive manner, in which an individual must carry both copies of the gene in a mutated form in all his/her cells, in order for the disease to manifest itself. Typically, both parents are unaffected carriers in such cases

In some cases, Congenital Generalized Fibromatosis arises sporadically and no preceding family history is observed.

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

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 Congenital Generalized Fibromatosis?

The common signs and symptoms associated with Congenital Generalized Fibromatosis include the following:

  • Presence of single or multiple tumorous nodules, which can be of the following types:
    • Solitary: It accounts for 75% of the reported cases. It is characterized by the presence of a single nodule on the skin, subcutaneous tissue, or muscle; but, rarely on the bone
    • Multicentric: This type has several nodules and the tumor involvement is limited to the skin and muscle
    • Multicentric with visceral involvement: It is the most severe form, with nodules on the skin, muscle, bone, and internal organs. The nodules can exist in a single or multiple internal organs
  • The nodules are generally firm and the color of flesh or purple-colored
  • The nodules can grow in size and cause pain
  • Overlying skin on the nodule may ulcerate and bleed

How is Congenital Generalized Fibromatosis Diagnosed?

The diagnosis of Congenital Generalized Fibromatosis generally involves the following:

  • A thorough physical examination
  • An assessment of the symptoms
  • An evaluation of family medical history
  • Imaging studies, such as magnetic resonance imaging (MRI), ultrasound, or computerized tomography (CT) scan, to view the location and size of the nodules
  • Genetic testing for confirmation of mutations in the affected individual
  • Biopsy of the nodules/lesions: A tissue biopsy is performed and sent to a laboratory for a pathological examination, who examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

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 Congenital Generalized Fibromatosis?

Complications that develop because of Congenital Generalized Fibromatosis are generally consistent with the type, location, size, and number of tumors that are present. However, the most important indication of the severity of the disorder is the involvement of the internal organs.

Some potential complications may include:

  • Neurological impairment, when the nervous system is involved
  • Gastrointestinal defects involving the stomach or intestine
  • Cardiopulmonary related conditions that may involve the heart and/or lungs

How is Congenital Generalized Fibromatosis Treated?

The treatment of Congenital Generalized Fibromatosis needs coordinated efforts from healthcare providers of different specialties.

  • In about half of the cases, CGF manifests immediately after birth with the tumors growing, developing, and receding spontaneously. Therefore, a ‘wait and watch’ approach is employed, depending on the size, numbers, location, and kind of tumors, following its diagnosis
  • When necessary, the most common method of treatment is a surgical removal of the tumor(s)
  • In cases where surgical removal of the tumor is not possible, either due to the location of the tumor, or the tumor being on a vital organ, chemotherapy may be used in treating the condition
  • Aggressive tumors may be treated using chemotherapy, radiotherapy, and steroid injections

How can Congenital Generalized Fibromatosis be Prevented?

Congenital General Fibromatosis is a genetic condition, and therefore, currently there are no guidelines or specific methods of preventing the condition from occurring.

  • 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 Congenital Generalized Fibromatosis (CGF)

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Congenital Generalized Fibromatosis? (Outcomes/Resolutions)

The prognosis of Congenital Generalized Fibromatosis depends on the location and number of tumors. It also depends upon the complications associated with the tumor.

  • The outcomes are generally good for superficial (on or just below the skin), small-sized, uncomplicated tumors
  • The prognosis may be poor when multiple tumors involving the internal organs, such as the heart, lung, gastrointestinal tract, etc. are noted. Such tumors can lead to gastrointestinal obstruction, breathing difficulties, chronic diarrhea, or heart abnormalities, and may even cause fatal outcomes

Additional and Relevant Useful Information for Congenital Generalized Fibromatosis:

After the onset of the tumors, regular imaging studies are generally not required to screen the tumors and assess the individual’s medical condition, unless visceral (vital organs) involvement is noted and the condition worsens rapidly.

What are some Useful Resources for Additional Information?

National Organization for Rare Disorders (NORD)
55 Kenosia Avenue Danbury, CT 06810
Phone: (203) 744-0100
Toll-Free: (800) 999-6673
Fax: (203) 798-2291
Email: orphan@rarediseases.org
Website: http://www.rarediseases.org

References and Information Sources used for the Article:

http://atlasgeneticsoncology.org/Kprones/CongMyofibromID10137.html (accessed on 12/06/2016)

http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/753/printFullReport (accessed on 12/06/2016)

http://www.omim.org/entry/228550 (accessed on 12/06/2016)

http://surgpathcriteria.stanford.edu/softfib/infantile_fibromatosis/printable.html (accessed on 12/06/2016)

Helpful Peer-Reviewed Medical Articles:

Wu, S. Y., McCavit, T. L., Cederberg, K., Galindo, R. L., & Leavey, P. J. (2015). Chemotherapy for generalized infantile myofibromatosis with visceral involvement. Journal of pediatric hematology/oncology, 37(5), 402-405.

Oudijk, L., den Bakker, M. A., Hop, W. C., Cohen, M., Charles, A. K., Alaggio, R., ... & de Krijger, R. R. (2012). Solitary, multifocal and generalized myofibromas: clinicopathological and immunohistochemical features of 114 cases. Histopathology, 60(6B), E1-E11.

Bhatkule, M. A., Dhawle, M. S., Kumbhakarna, N. R., & Bindu, R. S. (2015). Infantile myofibromatosis of uterus: A case report. Indian Journal of Cancer,52(3), 452.

Mashiah, J., Hadj-Rabia, S., Dompmartin, A., Harroche, A., Laloum-Grynberg, E., Wolter, M., ... & Bodemer, C. (2014). Infantile myofibromatosis: a series of 28 cases. Journal of the American Academy of Dermatology,71(2), 264-270

Wilson, M., Emil, S., Cowan, K., Kalechstein, S., Puligandla, P., Nguyen, V. H., ... & Chou, S. (2013). Infantile myofibromas obstructing opposite ends of the gastrointestinal tract. Journal of pediatric surgery, 48(2), 449-453.

Smith, A., & Orchard, D. (2011). Infantile myofibromatosis: two families supporting autosomal dominant inheritance. Australasian Journal of Dermatology, 52(3), 214-217.

Engel, M., Thiele, O., Mechtersheimer, G., Hoffmann, J., Freudlsperger, C., Freier, K., & Castrillon-Oberndorfer, G. (2011). Solitary infantile myofibroma of the skull. Journal of Craniofacial Surgery, 22(6), e66-e68.

Nirvikalpa, N., & Narayanan, V. (2011). Intraosseous infantile myofibroma of the mandible. Annals of maxillofacial surgery, 1(1), 87.

Kim, E. J., Wang, K. C., Lee, J. Y., Phi, J. H., Park, S. H., Cheon, J. E., ... & Kim, S. K. (2013). Congenital solitary infantile myofibromatosis involving the spinal cord: Case report. Journal of Neurosurgery: Pediatrics, 11(1), 82-86.