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Disease Profile

Infantile myofibromatosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

D48.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Congenital and Genetic Diseases; Nervous System Diseases; Rare Cancers;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 2591

Definition
A rare benign soft tissue tumor characterized by the development of nodules in the skin, striated muscles, bones, and in exceptional cases, visceral organs, leading to a broad spectrum of clinical symptoms. It contains myofibroblasts.

Epidemiology
The estimated prevalence is 1/150,000 live births.

Clinical description
Infantile myofibromatosis (IM) presents at birth or develops shortly thereafter, with 90% of cases occurring before the age of 2 years. IM is characterized by solitary or multiple nodules that are firm, flesh-colored to purple (''myofibroma''), and usually painless (except in case of compression of adjacent nerves). Tumors are located in the skin, subcutaneous tissue, striated muscles and in exceptional cases, visceral organs or bones. There are 4 patterns of clinical presentation: solitary (single lesion affecting the skin and/or muscles in the head, neck, or trunk (75% cases)); congenital multiple (multicentric limited to skin and muscles); congenital multiple with single visceral involvement; and congenital multiple with multiple visceral involvement (multiple lesions of skin and/or muscles, bones, lungs, heart and gastrointestinal tract). Rarely, prenatal diagnosis could be evoked.

Etiology
Most of these tumors are sporadic and isolated. Rare familial cases of IM have been described and 2 genes have been identified as disease causing: PDGFRB and NOTCH3 which encode PDGFRB and NOTCH3 respectively. PDGFRB is a tyrosine kinase receptor for platelet derived growth factors which are mitogens for cells of mesenchymal origin. PDGFRB expression is up regulated by NOTCH3. This suggests that genetic defects in the 2 genes are involved in the same mechanism.

Diagnostic methods
Diagnosis is evoked partly on family history and physical examination at this age. Myofibromas are identified through ultrasound (mass with an anechoic center), MRI (low signal on T1-weighted imaging and high or low signal intensity areas on T2-weighted imaging) and less frequently CT (mass with peripheral enhancement and calcifications). Histopathology remains the gold standard for the diagnosis of IM. Biopsy reveals interlacing fascicles of spindle cells (myofibroblasts) in the periphery. Immunochemistry reveals vimentin and smooth muscle actin expression while vascular markers (S100 and CD34) are negative. In some cases, molecular tumor analysis could found a PDGFRB gene mutation.

Differential diagnosis
Differential diagnosis in case of solitary lesion includes hemangioma, lymphangioma, neurofibroma, infantile fibrosarcoma, Langerhans cell histiocytosis, inflammatory myofibroblastic tumor, desmoid tumors and dermoid or epidermoid tumors.

Antenatal diagnosis
Prenatal diagnosis is achieved by ultrasound examination and confirm by fetal MRI.

Genetic counseling
IM is mostly isolated and sporadic. In cases of familial and multifocal lesions, IM can be inherited as an autosomal recessive or dominant trait (incomplete penetrance and variable expressivity).

Management and treatment
Due to the benignity of the lesion, therapies without long term effects are preferred. For lesions affecting the skin and/or muscles, treatment is not recommended and a wait-and-see policy is proposed (tendency towards spontaneous regression). Radical surgical excision is required if: vital organs are involved, lesions are in threatening sites, or lesions are symptomatic. In cases of incomplete resection, re-excision can be proposed later. Standard therapy is low dose weekly methotrexate and vinblastine and is indicated for multifocal progressive life threatening lesions. Other treatments such as conventional chemotherapy (vincristine, D-actinomycin, and cyclophosphamide) should be kept for patients with rapid symptomatic progression because of the long-term risks of secondary malignancy development. PDGFRB inhibitors have not already been studied in such disease.

Prognosis
In the majority of cases, which lack visceral involvement, prognosis is excellent and spontaneous regression is often observed. On the other hand, the presence of visceral lesions is associated with a significantly poor outcome and a mortality rate of up to 70%, in the absence of therapy. Death is generally related to organ compression and cardiopulmonary and gastrointestinal involvement.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Abnormality of the musculature
Muscular abnormality
0003011
Bone cyst
Bone cysts
0012062
Neoplasm of the skin
Skin tumors
Tumor of the skin

[ more ]

0008069
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin

[ more ]

0001482
30%-79% of people have these symptoms
Abnormal hair morphology
Abnormality of the hair
Hair abnormality

[ more ]

0001595
Abnormal skull morphology
Abnormality of the skull
0000929
Abnormal thorax morphology
Abnormality of the chest
0000765
Chondrocalcinosis
Calcium deposits in joints
0000934
Gingival fibromatosis
0000169
Neoplasm of the lung
Lung tumor
0100526
5%-29% of people have these symptoms
Abnormal sacrum morphology
0005107
Abnormality of the eye
Abnormal eye
0000478
Abnormality of the kidney
Abnormal kidney
0000077
Benign neoplasm of the central nervous system
0100835
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Hypercalcemia
High blood calcium levels
Increased calcium in blood

[ more ]

0003072
Intestinal obstruction
Bowel obstruction
Intestinal blockage

[ more ]

0005214
Irregular hyperpigmentation
0007400
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Neoplasm of the pancreas
Cancer of the pancreas
Pancreatic tumor

[ more ]

0002894
Osteolysis
Breakdown of bone
0002797
Skin ulcer
Open skin sore
0200042
Tracheoesophageal fistula
0002575
Percent of people who have these symptoms is not available through HPO
Abnormality of connective tissue
0003549
Autosomal dominant inheritance
0000006
Fibroma
0010614

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Infantile myofibromatosis. Click on the link to view a sample search on this topic.