National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Hyaline fibromatosis syndrome


Other Names:
Juvenile hyaline fibromatosis (former subtype); Puretic syndrome; Infantile systemic hyalinosis (former subtype); Juvenile hyaline fibromatosis (former subtype); Puretic syndrome; Infantile systemic hyalinosis (former subtype); Inherited systemic hyalinosis See More
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Hyaline fibromatosis syndrome (HFS) is a condition characterized by deposits of a clear substance (hyaline) in the skin and in various other body tissues. It typically becomes apparent at birth or in infancy, causing severe pain with movement; progressive joint contractures which limit movement; thickened skin; and hyperpigmented patches over prominences of the joints. Other features may include digestive problems; gum enlargement; skin bumps; pearly papules on the face and neck; and masses near the anus (perianal masses). Complications can be life threatening. Many children with the severe form (previously called infantile systemic hyalinosis) die in early childhood, while some with a milder form (previously called juvenile hyaline fibromatosis) survive into adulthood.[1] HFS is caused by mutations in the ANTXR2 gene and is inherited in an autosomal recessive manner.[2] Treatment is supportive and aims to alleviate pain and other signs and symptoms of the condition.[1]
Last updated: 1/7/2016

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal diaphysis morphology
Abnormal shape of shaft of long bone
Abnormality of shaft of long bone of the limbs
[ more ] 		0000940
Abnormal hair morphology
Abnormality of the hair
Hair abnormality
[ more ] 		0001595
Abnormal skull morphology
Abnormality of the skull
0000929
Abnormality of dental morphology
Abnormality of dental shape
Abnormally shaped teeth
Deformity of teeth
Dental deformity
Dental malformations
Malformed teeth
Misshapen teeth
Misshapened teeth
[ more ] 		0006482
Abnormality of the adrenal glands
Adrenal abnormalities
0000834
Aplasia/Hypoplasia of the thymus
Absent/small thymus
Absent/underdeveloped thymus
[ more ] 		0010515
Brachydactyly
Short fingers or toes
0001156
Camptodactyly of finger
Permanent flexion of the finger
0100490
Chronic diarrhea 0002028
Coarse facial features
Coarse facial appearance
0000280
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
Gingival overgrowth
Gum enlargement
0000212
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Immunodeficiency
Decreased immune function
0002721
Joint stiffness
Stiff joints
Stiff joint
[ more ] 		0001387
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Micromelia
Smaller or shorter than typical limbs
0002983
Muscular hypotonia
Low or weak muscle tone
0001252
Osteomalacia
Softening of the bones
0002749
Osteopenia 0000938
Osteoporosis 0000939
Papule 0200034
Polycystic ovaries 0000147
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections
[ more ] 		0002718
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures
[ more ] 		0002757
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe
[ more ] 		0003510
Short neck
Decreased length of neck
0000470
Short palm 0004279
Skin ulcer
Open skin sore
0200042
Steatorrhea
Fat in feces
0002570
Subcutaneous nodule
Growth of abnormal tissue under the skin
Firm lump under the skin
[ more ] 		0001482
Telangiectasia of the skin 0100585
Thickened skin
Thick skin
0001072
Urticaria
Hives
0001025
30%-79% of people have these symptoms
Aplasia/Hypoplasia of the skin
Absent/small skin
Absent/underdeveloped skin
[ more ] 		0008065
Death in infancy
Infantile death
Lethal in infancy
[ more ] 		0001522
5%-29% of people have these symptoms
Abnormality of the gastrointestinal tract 0011024
Gingival fibromatosis 0000169
Osteolysis
Breakdown of bone
0002797
Progressive flexion contractures 0005876
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Diarrhea
Watery stool
0002014
Progressive
Worsens with time
0003676
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection
[ more ] 		0002719
Variable expressivity 0003828
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Last updated: 7/1/2020
Hyaline fibromatosis syndrome is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
  • 25% (1 in 4) chance to be affected
  • 50% (1 in 2) chance to be an unaffected carrier like each parent
  • 25% chance to be unaffected and not be a carrier.
Once an at-risk sibling of an affected person is known to be unaffected, the chance for that sibling to be a carrier is about 67% (2 in 3).

If the disease-causing mutations have been identified in an affected family member, prenatal testing for at-risk pregnancies may be available. The use of prenatal ultrasound for detecting HFS is unclear, but in a pregnancy at risk, detecting decreased fetal activity and contractures could suggest recurrence. Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutations have been identified.[1]

People with a family history of HFS are encouraged to speak with a genetic counselor or other genetics professional.
Last updated: 1/8/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
It has been suggested that physical therapy may help to treat joint contractures in juvenile hyaline fibromatosis; this therapy should be done with an awareness of the pain tolerance of each affected individual.  Splinting may help reduce pain associated with contractures by stabilizing the joint.[3]
Last updated: 2/16/2012
The severity of hyaline fibromatosis syndrome (HFS) can vary broadly. The long-term outlook (prognosis) for people with HFS depends on how severely a person is affected. Overall, the prognosis is poor, especially for those with systemic involvement.[4] The disorder typically progresses, with the continual appearance of new lesions.[5] However, even within severe and mild forms, the degree of severity and specific signs and symptoms can vary. This spectrum of severity and features is the reason that the terms 'hyaline fibromatosis syndrome' or 'inherited systemic hyalinosis' are now used, rather than terms defining severe (infantile) and milder (juvenile) forms as distinct entities.[1]

Children with severe forms (previously called infantile systemic hyalinosis) often don't survive past early childhood. Some with milder forms (previously called juvenile hyaline fibromatosis) survive into adulthood.[1] Although joint contractures, skin hyperpigmentation, and lesions occur with the milder form, the other features may vary, the pain is less severe, and disability may be less pronounced. Pain may lessen with age.[1] Risks of potentially life-threatening complications in people with HFS may be due to persistent diarrhea, infections, and malnutrition.[5] There is currently no cure for HFS, and treatment generally aims to alleviate signs and symptoms.

While cognitive function is typically normal, cases of delayed development have been reported.[1]
Last updated: 1/8/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Juvenile hyaline fibromatosis, Winchester syndrome, lipoid proteinosis (Urbach-Wiethe disease) and mucopolysaccharidosis type II (Hunter's syndrome) should be considered in the differential diagnosis (see these terms).
Visit the Orphanet disease page for more information.

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

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
    GeneReviews
  • 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.
    Juvenile hyaline fibromatosis
    Infantile systemic hyalinosis
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Hyaline fibromatosis syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Joseph TC Shieh, H Eugene Hoyme, and Laura T Arbour. Hyalinosis, Inherited Systemic. GeneReviews. April 11, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1525/.
  2. Cassandra L. Kniffin. HYALINE FIBROMATOSIS SYNDROME; HFS. OMIM. January 14, 2013; http://www.omim.org/entry/228600.
  3. Shieh JTC, Hoyme HE, Arbour LT. Inherited Systemic Hyalinosis. GeneReviews. February 2008; http://www.ncbi.nlm.nih.gov/books/NBK1525/. Accessed 2/13/2012.
  4. Bernárdez C, Martinez Barba E, Kutzner H, Requena L. A mild case of hyaline fibromatosis syndrome, presenting in an adult. J Eur Acad Dermatol Venereol. March 23, 2015; [Epub ahead of print]:
  5. Van Raak SM, Meuffels DE, Van Leenders GJ, Oei EH. Hyaline fibromatosis of Hoffa's fat pad in a patient with a mild type of hyaline fibromatosis syndrome. Skeletal Radiol. April, 2014; 43(4):531-534.