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Infantile Myofibromatosis

NORD gratefully acknowledges Wendy K. Chung, MD, PhD, Department of Pediatrics, Columbia University, for assistance in the preparation of this report.

Synonyms of Infantile Myofibromatosis

  • congenital generalized fibromatosis
  • IM
  • juvenile myofibromatosis

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Infantile myofibromatosis is a rare disorder characterized by the growth of one or more benign (noncancerous) tumors. The skin, bone, muscle, soft tissue, and, in rare cases, the internal organs (viscera) can be affected. The severity and specific symptoms present varies greatly from one person to another based, in part, upon the specific location and number of tumors. These tumors do not spread (metastasize), but can grow large enough to cause symptoms by compressing or damaging nearby organs or other parts of the body. Most cases affect infants or young children, but adult cases have been described in the medical literature. Most cases of infantile myofibromatosis occur randomly for no apparent reason (sporadically). However, familial cases (in which more than one family member is affected) have been identified; two different genes, PDGFRB and NOTCH3, have been determined to cause some of these cases. Treatment depends upon the location of the lesion(s). Spontaneous regression has been reported to occur in many cases; however, recurrence of the lesions has also been reported. Surgery is the main treatment option.

Infantile myofibromatosis was first described as a distinct entity in the medical literature in 1954 by Dr. A.P. Stout. The disorder was initially referred to as congenital generalized fibromatosis. Additional cases were reported in the medical literature under a variety of names including multiple congenital fibromatosis, multiple hamartomas, multiple vascular leiomyomatosis of the newborn, and multiple congenital fibromatosis. In 1981, Drs. Chung and Enzinger provided a detailed review of the disorder and introduced the name infantile myofibromatosis.


The specific symptoms and severity of infantile myofibromatosis is broad. Some infants have mild disease that resolves on its own without treatment (spontaneous regression). Others develop extensive disease that involves internal organs and can cause life-threatening complications if left untreated. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below and that every individual case is unique. Parents should talk to their child’s physician and medical team about their specific case, associated symptoms and overall prognosis.

The tumors or lesions that characterize infantile myofibromatosis are usually seen as firm, flesh or purple covered bumps (nodules) on the skin or just underneath the top layer of the skin (subcutaneous layer). These superficial lesions may be freely movable; deeper lesions are generally immovable. Skin lesions may be crusted or hardened (indurated). The lesions are usually not painful or tender. The overlying skin may be discolored red or purple and ulcerated. Lesions are also commonly found in muscle, soft tissue and bone.

Although the tumors that characterize infantile myofibromatosis do not spread, they can grow large enough to damage or compress nearby structures in the body. Pain, which occurs when tumors press against adjacent nerves, can develop. In some cases, tumor growth can also cause bone destruction, disfigurement, and even physical limitations. More than 90% of cases have onset in infancy, although the disorder can first present later in childhood or less often in adults. The tumors can continue to develop throughout an affected individual’s life.

Infantile myofibromatosis is sometimes broken down into separate types, specifically solitary, multicentric, and multicentric with visceral involvement. The solitary form occurs predominantly in males. The multicentric forms are more common in females.

The solitary form is characterized by one nodule or lesion that most commonly occurs in the skin and often extends into subcutaneous tissue and/or muscle tissue. These nodules are usually found in the head, neck and trunk areas. A solitary nodule of the bone can also occur, but is extremely rare. The solitary form is most common, accounting for approximately 75% of cases of infantile myofibromatosis.

The multicentric form without visceral involvement is generally limited to the skin, subcutaneous tissue and muscle. This form is characterized by multiple nodules that can arise in different areas of the skin, subcutaneous tissue or muscle.

The multicentric form with visceral involvement is the most severe form of the disorder and is characterized by multiple growths of the skin, muscles, and bones along with the involvement of the internal organs such as the lungs, heart, and gastrointestinal tract. In some cases, only one organ may be involved; in other cases visceral involvement is widespread. This form of infantile myofibromatosis can cause severe, life-threatening complications depending upon the exact location of the lesion and the specific organs involved.


Most cases of infantile myofibromatosis are believed to occur spontaneously and without a known family history of the disorder. In these cases, the underlying cause of the disorder is unknown. However, rare cases have been identified that run in families, and mutations in two genes have been identified as causing the disorder in some cases. These genes are the platelet-derived growth factor receptor beta (PDGFRB) gene and the NOTCH3 gene.

Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect the body.

In infantile myofibromatosis, mutations in the platelet-derived growth factor receptor beta PGDFRB gene may occur as a new (sporadic or de novo) mutation, which means that the gene mutation has occurred new in the child. When the gene mutation is passed from one generation to the next (as it can be in the children of the individual with a de novo mutation), it is inherited in an autosomal dominant manner. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent. The risk of passing the abnormal gene from affected parent to the child is 50% for each pregnancy regardless of the sex of the child.

Autosomal dominant forms of infantile myofibromatosis may manifest slightly differently in different members of the family. Not all family members will have myofibromas in exactly the same place or at exactly the same age.

Mutations in the NOTCH3 gene have been described in one family. This mutation is believed to be inherited in an autosomal recessive manner. Recessive genetic disorders occur when an individual inherits a mutation in the gene from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass on the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a healthy carrier like the parents is 50% with each pregnancy. The chance for a child to receive two normal genes and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

Affected Populations

Infantile myofibromatosis affects males and females in equal numbers. Some reports have noted that males are affected more often by the solitary form and females are affected more often by multicentric forms. The exact incidence is unknown, but is estimated to be between 1 in 150,000 to 400,000 live births. Because cases can go undiagnosed or misdiagnosed, determining the true frequency in the general population is difficult. Although rare, infantile myofibromatosis is the most common fibrous tumor in infancy and early childhood.

Related Disorders

Symptoms of the following disorders can be similar to those of infantile myofibromatosis. Comparisons may be useful for a differential diagnosis.

There are numerous benign or malignant soft tissue and other types of tumors that can superficially resemble the lesions associated with infantile fibromatosis. Such conditions include nodular fasciitis, pediatric sarcomas, desmoid tumors, inflammatory myofibroblastic tumors, neurofibromas, hemangiomas, lymphangiomas, infantile fibrosarcomas, fibrous hamartomas of infancy, and dermoid or epidermoid tumors. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

There are a number of additional syndromes such as neurofibromatosis type 1 that may be characterized by the formation of single or multiple soft tissue, bony, and/or other tumors that superficially resemble those associated with infantile myofibromatosis. However, such syndromes typically may be distinguished by the presence of other characteristic symptoms and physical findings. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Standard Therapies

A diagnosis of infantile myofibromatosis is based upon the examination of the tissue in a patient with characteristic symptoms and physical examination. Imaging studies including ultrasound and MRI are most often used to visualize the extent of the growths. Imaging techniques may be used to assess the extent of the growths, the progression of the growths, and to diagnose recurrence of a growth. Imaging may be used to help evaluate the size, placement, and extension of lesions and to aid surgical procedures.

A definitive diagnosis of infantile myofibromatosis requires removal and microscopic examination of affected tissue to determine the pathology. Such examination reveals unique characteristics of the affected tissue, which distinguishes the growths of infantile myofibromatosis from other growths or masses that otherwise appear similar on imaging studies.

Molecular genetic testing from a blood sample can confirm a genetic cause for infantile myofibromatosis in specific cases. Molecular genetic testing can detect mutations in specific genes known to cause the disorder, but is available only at specialized genetic laboratories.

The treatment of infantile myofibromatosis is directed toward the specific symptoms in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedists, dermatologists, and other healthcare professionals may need to work together to plan a child’s treatment. Genetic counseling may be of benefit for families. Psychosocial support for the entire family is essential as well.

There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with infantile myofibromatosis.

Specific therapeutic procedures and interventions may vary, depending upon size, number and location(s) of the lesion(s) and symptoms. Decisions concerning the use of particular drug regimens, surgical treatments and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.

In many cases, infantile myofibromatosis lesions go away on their own without treatment (spontaneous remission). The initial treatment option for many individuals is watchful waiting and observation with appropriate patient education. Watchful waiting or “wait and watch” refers to when physicians follow certain patients with infantile myofibromatosis (i.e. those without visceral involvement or problematic symptoms) without giving treatment until progression of the disease occurs. This allows some people to avoid undergoing surgery or other treatment options for many years or all together in cases with eventual spontaneous remission.

The main treatment option for individuals with infantile myofibromatosis is surgery, which is performed to prevent complications or improve prognosis. Surgical removal of lesions is reserved for cases where there is involvement of internal organs (viscera), symptomatic lesions, or lesions that present an immediate threat due to their location near vital organs and/or if they have shown progression. In approximately 10% of cases, lesions may recur after surgery.

Chemotherapy may be used to treat cases where there is involvement of the internal organs and surgery was unsuccessful (i.e. lesions recur) or where surgery is not possible (unresectable) due to the location of the lesions (e.g. too close to a vital organ). Affected children have been successfully treated with a combination of methotrexate and vinblastine. In other cases, interferon alfa or a combination of vincristine, actinomycin D, and cyclophosphamide have also been used successfully, but may be reserved for individuals with rapid progression of symptoms.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources, in the main, contact:

For more information about clinical trials conducted in Europe, contact:

Infantile Myofibromatosis Resources



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Mashiah J, Hadj-Rabia S, Dompmartin A, et al. Infantile myofibromatosis: a series of 28 cases. J Am Acad Dermatol. 2014;71:264-270.

Wu SY, McCavit TL, Cederberg K, Galindo RL, Leavey PJ. Chemotherapy for generalized infantile myofibromatosis with visceral involvement. J Pediatr Hematol Oncol. 2014;[Epub ahead of print].

Linhares ND, Freire MC, Cardenas RG, et al. Modulation of expressivity in PDGFRB-related infantile myofibromatosis: a role for PTPRG? Genet Mol Res. 2014;13:6287-6292.

Cheung YH, Gayden T, Campeau PM, et al. A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet. 2013;92:996-1000.

Martignetti JA, Tian L, Li D, et al. Mutations in PDGRFB cause autosomal dominant infantile myofibromatosis. Am J Hum Genet. 2013;92:1001-1007.

Lee JW. Mutations in PDGFRB and NOTCH3 are the first genetic causes identified for autosomal dominant infantile myofibromatosis. Clin Genet. 2013;84:340-341.

Levine E, Freneux P, Schleiermacher G, et al. risk-adapted therapy for infantile myofibromatosis in children. Pediatr Blood Caner. 2012;59:115-120.

Hausbrandt PA, Leithner A, Beham A, et al. A rare case of infantile myofibromatosis and review of literature. J Pediatr Orthop B. 2010;19:122-126.

Auriti C, Kieran MW, Deb G, et al. Remission of infantile generalized myofibromatosis after interferon alpha therapy. J Pediatr Hematol Oncol. 2008;30:179-181.

Arcangeli F, Calista D. Congenital myofibromatosis in two siblings. Eur J Dermatol. 2006;16:181-183.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:228550; Last Update:07/08/2013. Available at: Accessed November 18, 2014.

Orbach D. Infantile Myofibromatosis. Orphanet Encyclopedia, November 2013. Available at: Accessed November 18, 2014.

Hatzidaki EG, Giannakopoulou CC. Infantile Myofibromatosis. Orphanet Encyclopedia, March 2005. Available at: Accessed November 18, 2014.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2014/11/20 00:00:00 GMT+0

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