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Hyaline fibromatosis syndrome(HFS)

MedGen UID:
1805033
Concept ID:
C5574677
Disease or Syndrome
Synonyms: HFS; Hyalinosis, Inherited Systemic; HYALINOSIS, SYSTEMIC
SNOMED CT: Hyaline fibromatosis syndrome (1197494003)
 
Gene (location): ANTXR2 (4q21.21)
 
Monarch Initiative: MONDO:0009229
OMIM®: 228600
Orphanet: ORPHA498474

Disease characteristics

Excerpted from the GeneReview: Hyaline Fibromatosis Syndrome
Hyaline fibromatosis syndrome (HFS) is characterized by hyaline deposits in the papillary dermis and other tissues. It can present at birth or in infancy with severe pain with movement, progressive joint contractures, and often with severe motor disability, thickened skin, and hyperpigmented macules/patches over bony prominences of the joints. Gingival hypertrophy, skin nodules, pearly papules of the face and neck, and perianal masses are common. Complications of protein-losing enteropathy and failure to thrive can be life threatening. Cognitive development is normal. Many children with the severe form (previously called infantile systemic hyalinosis) have a significant risk of morbidity or mortality in early childhood; some with a milder phenotype (previously called juvenile hyaline fibromatosis) survive into adulthood. [from GeneReviews]
Authors:
Joseph TC Shieh  |  H Eugene Hoyme  |  Laura T Arbour   view full author information

Additional description

From OMIM
Hyaline fibromatosis syndrome is an autosomal recessive condition characterized by abnormal growth of hyalinized fibrous tissue usually affecting subcutaneous regions on the scalp, ears, neck, face, hands, and feet. The lesions appear as pearly papules or fleshy nodules. The severity is variable. Some individuals present in infancy and have additional visceral or systemic involvement, which can lead to early death. These patients may show intractable diarrhea and increased susceptibility to infection. Other patients have later onset of a milder disorder affecting only the face and digits. Additional features include gingival hypertrophy, progressive joint contractures resulting in severe limitation of mobility, osteopenia, and osteoporosis. Histologic analysis of skin lesions shows proliferation of spindle-shaped cells forming strands in a homogeneous and hyaline eosinophilic extracellular material in the dermis (summary by Denadai et al., 2012).  http://www.omim.org/entry/228600

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Gingival fibromatosis
MedGen UID:
42017
Concept ID:
C0016049
Finding
The presence of fibrosis of the gingiva.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Progressive flexion contractures
MedGen UID:
480952
Concept ID:
C3279322
Finding
Progressively worsening joint contractures.
Osteolysis
MedGen UID:
1648424
Concept ID:
C4721411
Pathologic Function
Osteolysis refers to the destruction of bone through bone resorption with removal or loss of calcium.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Subcutaneous nodule
MedGen UID:
101803
Concept ID:
C0151811
Pathologic Function
Slightly elevated lesions on or in the skin with a diameter of over 5 mm.
Thickened skin
MedGen UID:
66024
Concept ID:
C0241165
Finding
Laminar thickening of skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyaline fibromatosis syndrome

Professional guidelines

PubMed

Casas-Alba D, Martínez-Monseny A, Pino-Ramírez RM, Alsina L, Castejón E, Navarro-Vilarrubí S, Pérez-Dueñas B, Serrano M, Palau F, García-Alix A
Hum Mutat 2018 Dec;39(12):1752-1763. Epub 2018 Sep 17 doi: 10.1002/humu.23638. PMID: 30176098

Recent clinical studies

Etiology

Al Kaissi A, Hilmi M, Betadolova Z, Bouchoucha S, Trofimova S, Shboul M, Rustamov G, Dwera W, Sigl K, Kenis V, Kircher SG
Afr J Paediatr Surg 2021 Oct-Dec;18(4):224-230. doi: 10.4103/ajps.AJPS_162_20. PMID: 34341308Free PMC Article
Cozma C, Hovakimyan M, Iurașcu MI, Makhseed N, Selim LA, Alhashem AM, Ben-Omran T, Mahmoud IG, Al Menabawy NM, Al-Mureikhi M, Martin M, Demuth L, Yüksel Z, Beetz C, Bauer P, Rolfs A
Orphanet J Rare Dis 2019 Aug 27;14(1):209. doi: 10.1186/s13023-019-1183-5. PMID: 31455396Free PMC Article
Yonel Z, Parma S, Chapple IL
Dent Update 2015 Sep;42(7):656-8, 660-2, 665-6. doi: 10.12968/denu.2015.42.7.656. PMID: 26630863
Çam B, Kurkcu M, Ozturan S, Haytac C, Uguz A, Ogden G
Int J Dermatol 2015 Feb;54(2):217-21. Epub 2014 Feb 10 doi: 10.1111/ijd.12033. PMID: 24506420
Giri PP, Raushan R, Ghosh A, Pal P
Indian Pediatr 2012 Jan;49(1):62-4. PMID: 22318104

Diagnosis

Daşar T, Gönen HN, Kösemehmetoğlu K, Tekşam Ö, Boduroğlu K, Utine GE, Şimşek Kiper PÖ
Turk J Pediatr 2024 May 23;66(2):205-214. doi: 10.24953/turkjpediatr.2024.4511. PMID: 38814306
Pereira TDSF, Sales JF, Travassos DV, Lanza CR, Castro WH, Gomes CC, Fonseca FP, Silva TA, Gomez RS
Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Dec;130(6):e328-e335. Epub 2020 Jul 4 doi: 10.1016/j.oooo.2020.06.022. PMID: 32771412
Folpe AL, Schoen M, Kang S
Mayo Clin Proc 2020 Feb;95(2):328-329. doi: 10.1016/j.mayocp.2019.11.021. PMID: 32029086
Ravikumar VR, Veerappan Ramamoorthi RG, Manisankar S
Indian J Pathol Microbiol 2019 Apr-Jun;62(2):300-302. doi: 10.4103/IJPM.IJPM_76_17. PMID: 30971561
Marques SA, Stolf HO, Polizel JO, Munhoz T, Brandão MC, Marques ME
An Bras Dermatol 2016 Apr;91(2):226-9. doi: 10.1590/abd1806-4841.20163799. PMID: 27192526Free PMC Article

Therapy

Yoshikawa M, Shinomura T, Kishimoto K, Uga H
A A Pract 2020 Feb 1;14(3):87-89. doi: 10.1213/XAA.0000000000001156. PMID: 31842195
Einecke G, Reeve J, Halloran PF
Am J Transplant 2018 Apr;18(4):821-831. Epub 2017 Nov 10 doi: 10.1111/ajt.14532. PMID: 28985016

Prognosis

Daşar T, Gönen HN, Kösemehmetoğlu K, Tekşam Ö, Boduroğlu K, Utine GE, Şimşek Kiper PÖ
Turk J Pediatr 2024 May 23;66(2):205-214. doi: 10.24953/turkjpediatr.2024.4511. PMID: 38814306
Härter B, Benedicenti F, Karall D, Lausch E, Schweigmann G, Stanzial F, Superti-Furga A, Scholl-Bürgi S
Mol Genet Genomic Med 2020 Jun;8(6):e1203. Epub 2020 Mar 20 doi: 10.1002/mgg3.1203. PMID: 32196989Free PMC Article
Ravikumar VR, Veerappan Ramamoorthi RG, Manisankar S
Indian J Pathol Microbiol 2019 Apr-Jun;62(2):300-302. doi: 10.4103/IJPM.IJPM_76_17. PMID: 30971561
Casas-Alba D, Martínez-Monseny A, Pino-Ramírez RM, Alsina L, Castejón E, Navarro-Vilarrubí S, Pérez-Dueñas B, Serrano M, Palau F, García-Alix A
Hum Mutat 2018 Dec;39(12):1752-1763. Epub 2018 Sep 17 doi: 10.1002/humu.23638. PMID: 30176098
Giri PP, Raushan R, Ghosh A, Pal P
Indian Pediatr 2012 Jan;49(1):62-4. PMID: 22318104

Clinical prediction guides

Futagawa H, Ito S, Hosoi K, Tamada I, Ogata K, Fukuda K, Yamanaka H, Kuroda M, Suda C, Shimizu K, Yoshihashi H
Pediatr Int 2024 Jan-Dec;66(1):e15797. doi: 10.1111/ped.15797. PMID: 39258861
Al Kaissi A, Hilmi M, Betadolova Z, Bouchoucha S, Trofimova S, Shboul M, Rustamov G, Dwera W, Sigl K, Kenis V, Kircher SG
Afr J Paediatr Surg 2021 Oct-Dec;18(4):224-230. doi: 10.4103/ajps.AJPS_162_20. PMID: 34341308Free PMC Article
Cozma C, Hovakimyan M, Iurașcu MI, Makhseed N, Selim LA, Alhashem AM, Ben-Omran T, Mahmoud IG, Al Menabawy NM, Al-Mureikhi M, Martin M, Demuth L, Yüksel Z, Beetz C, Bauer P, Rolfs A
Orphanet J Rare Dis 2019 Aug 27;14(1):209. doi: 10.1186/s13023-019-1183-5. PMID: 31455396Free PMC Article
Gao Y, Bai J, Wang J, Liu X
Mol Med Rep 2018 Oct;18(4):4004-4008. Epub 2018 Aug 22 doi: 10.3892/mmr.2018.9421. PMID: 30152846
Rahvar M, Teng J, Kim J
Am J Dermatopathol 2016 May;38(5):e60-3. doi: 10.1097/DAD.0000000000000467. PMID: 26885603

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