Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Case Report
2008:74:4;371-374
doi: 10.4103/0378-6323.42913
PMID: 18797061

Juvenile hyaline fibromatosis and infantile systemic hyalinosis: Divergent expressions of the same genetic defect?

Mandeep Dhingra, Sangeeta Amladi, Shankar Savant, Chitra Nayak
 Department of Derrmatology, T.N. Medical College and B.Y.L. Nair Ch. Hospital, Mumbai Central, Mumbai - 400 008, India

Correspondence Address:
Mandeep Dhingra
Department of Dermatology, OPD-14, 'O' bldg. 2nd floor, T.N. Medical college and B.Y.L. Nair Ch.Hospital, Dr. A.L. Nair Road, Mumbai Central. Mumbai- 400 008
India
How to cite this article:
Dhingra M, Amladi S, Savant S, Nayak C. Juvenile hyaline fibromatosis and infantile systemic hyalinosis: Divergent expressions of the same genetic defect?. Indian J Dermatol Venereol Leprol 2008;74:371-374
Copyright: (C)2008 Indian Journal of Dermatology, Venereology, and Leprology

Abstract

We describe here a three year-old girl with classic clinical and histological features of juvenile hyaline fibromatosis. We found a history of similar skin findings in her eldest sister, in whom the disorder took a rapidly progressive and fatal course in the second year of life, suggesting either a very severe form of juvenile hyaline fibromatosis, or the possibility of infantile systemic hyalinosis. The similarities and differences between these two described types of hyalinoses have been reviewed in reference to the present report.
Keywords: Allelic disorders, Fibromatosis, Hyalinosis

Introduction

Hyalinoses are rare autosomal recessive disorders in which there is an accumulation of amorphous hyaline material in the skin and other organs. Two distinct forms have been described: juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH).

Juvenile hyaline fibromatosis is characterized by papulonodular skin lesions, gingival hyperplasia, joint contractures, and osteolytic bone lesions. Skin lesions may consist of multiple large tumors, commonly found on the scalp and the neck, and small pearly, pink papules and plaques on the trunk, chin, ears, and around the nostrils. [1]

The clinical features of infantile systemic fibromatosis include a diffuse thickening of the skin, papulonodular skin lesions, hyperpigmentation over the metacarpophalangeal joints of the hands and malleoli, osteoporosis of bones, bone fractures, short stature, persistent diarrhea, and failure to thrive. [1]

Case Report

A three year-old girl was brought by her mother with complaints of asymptomatic, red colored, raised lesions prevalent since she was one year of age, on her nose, perioral area and ears. She had delayed milestones with restriction of speech to a few meaningful words only. She was unable to stand without support and had recurrent episodes of diarrhea. She had no history of joint contractures, convulsions or hoarseness of voice. She was born at full term by normal delivery following an uneventful pregnancy. Her parents had third degree consanguinity and were both unaffected. The middle sister aged five years, was unaffected by the disorder.

Her eldest sister however, born six years earlier, had developed identical, papular skin lesions on the face early in the neonatal period which gradually increased in size and number. As per the mother′s history, she had shown restriction of movement of the right upper limb since early infancy. She did not have thickened skin but was malnourished and had been chronically unwell with multiple hospital admissions for recurrent episodes of pneumonia and diarrhea. She had died at age of 1½ years of some cardiac problem, the details of which were unavailable.

Examination of our index case showed that she was short for her age (height 75 cm). Her weight was 10 kg implying grade-I malnutrition. The child was responsive to her surroundings, but could speak only a few meaningful words and was unable to support herself in the standing position due to muscle weakness.

Cutaneous examination revealed the presence of 1-5 mm, multiple, skin-colored and pink papules over the face and ear lobes. They were darker, clustered together and confluent on the mid-face, especially the nose, nasolabial folds and chin [Figure - 1]. Tiny papules were visible on the eyelids. Ulceration and discharge was evident from the nasal lesions, suggesting secondary infection. The trunk and limbs were spared. There was a single, large, soft, reddish nodule, 5 cm in size in the perianal area. Examination of the oral cavity revealed gingival hyperplasia; dentition was normal. Systemic examination did not reveal any abnormality.

The patient was found to be moderately mentally retarded with an IQ of 50. A complete hemogram, renal function tests, liver function tests, blood sugar and electrolytes were within normal limits. X-rays of the chest and bones were normal. Electrocardiograpy and 2D-echocardiography did not reveal any cardiac abnormality. Skin biopsy of the lesions showed a normal epidermis with deposits of amorphous, eosinophilic hyaline material throughout the upper and mid dermis. There was an abundance of stroma with a relative paucity of cellular elements. Numerous spindle-shaped, fibroblast-like cells were seen in the vicinity of the deposits [Figure - 2]. On special staining, the deposits were seen to be Periodic Acid-Schiff (PAS)-positive, Congo red-negative and Alcian blue-negative.

The child was diagnosed as a case of juvenile hyaline fibromatosis. Although we had not examined the eldest sister, her features as per her mother′s history are suggestive of a severe and rapidly fatal form of JHF or possibly ISH [Table - 1]. The parents were counselled about the progressive nature of the disease and the 25% chance of development of disease in future offspring. The patient is currently undergoing physiotherapy for the improvement of muscle strength.

Discussion

Juvenile hyaline fibromatosis (synonyms: juvenile hyalinosis, fibromatosis hyalinica multiplex, Murray-Puretic-Drescher syndrome) [2] is a rare, autosomal recessive, hereditary disease with distinct clinical and histopathological features. A survey of literature revealed < 70 cases reported worldwide [3] and only a handful of case reports from India. [3],[4] There is no sex predilection. The baby is normal at birth but abnormalities develop during the first two years and are relentlessly progressive. [2] Gingival hypertrophy often develops in the first year of life. The papules are distributed about the nose, behind the ears, in the genital area and on the thighs. Joint contractures often develop. Several large nodules and tumors develop between two and five years of age. Infection often results from ulceration of the lesions. [2] Adolescent patients are usually disfigured and bedridden due to their contractures. [5],[6] Partial disease expression is common. [7]

Infantile systemic hyalinosis (infantile hyaline fibromatosis, infantile hyalinoses) [2] is a disorder clinically similar to juvenile hyaline fibromatosis, but with far more severe joint involvement, joint contractures and thickened skin. Infants are affected within the first few weeks or months of life. Recurrent purulent infections, diarrhea and severe osteoporosis are observed in the first year of life. Severe joint limitation and pain lead to immobility and respiratory insufficiency. Feeding problems, malnutrition and protein-losing enteropathy are caused by the thickening and hyaline infiltration of intestinal walls. Death occurs secondary to sepsis with renal, respiratory and heart failure, usually by the age of two years. [8],[9]

It appears that both the conditions are linked to a disorder of the synthesis of glycosaminoglycans with resulting abnormality in collagen synthesis. The gene locus has been found on chromosome 4q21. [2] Mutations in the capillary morphogenesis gene-2 ( CMG2 ) have been found recently. [10] Histology shows the deposition of an amorphous, eosinophilic hyaline material in the extracellular spaces of the dermis around the blood vessels. There is an abundance of stroma with a relative paucity of cellular elements. The dermis contains a few inflammatory cells and widely scattered spindle cells disposed in a densely eosinophilic background. [2] The deposits are PAS-positive and Alcian blue-negative. Differential diagnosis of hyaline deposits in the skin includes disorders such as amyloidosis, lipoid proteinosis, and Waldenstr φm`s macroglobulinemia. They can also be seen in gouty tophi (if fixed in an aqueous fixative), colloid milium and at corticosteroid injection sites. Perivascular hyaline deposits are a feature of porphyria, especially erythropoietic protoporphyria. [11]

Both the disorders are allelic [10] and intermediate phenotypes between these two disorders have been described. It has been suggested that both disorders constitute parts of the same disease. [1] Patients with severe forms of JHF with persistent diarrhea and death in early infancy due to infections, have been reported. [1] Postmortem findings in another case with typical lesions of JHF strongly resembled those of ISH. In our reported family, the eldest sibling had features suggesting a diagnosis of a severe and rapidly fatal form of JHF or possibly ISH. This occurrence of two different ends of the spectrum of disease in siblings reiterates the view that both these conditions constitute parts of the same disease.

Other differential diagnoses include neurofibromatosis, gingival hyperplasia, nodular amyloidosis, congenital generalised fibromatosis, Winchester syndrome, and lipoid proteinosis. [3] Inborn metabolic disorders such as Farber`s disease, mucopolysaccharidoses and I-cell disease should also be considered in differential diagnosis. Gingival fibromatosis is not associated with cutaneous lesions typical of hyalinosis. Winchester syndrome is always associated with corneal clouding. Lipoid proteinosis can be differentiated on clinical grounds as well as by the demonstration of deposition of a amorphous, eosinophilic, hyaline material within the dermis with an onion skin arrangement around blood vessels. Inborn errors of metabolism can be differentiated on the basis of histological and biochemical findings. [2]

No specific treatment is available. Early surgical excision is recommended by some authors in JHF to prevent the appearance of new lesions, [12] although excision may be followed by recurrences. [5] Intralesional steroids may reduce the size of early lesions. Excision is indicated only for those lesions that either present a significant cosmetic problem or produce some degree of functional impairment. Capsulotomy of joints may show some temporary, beneficial effect; radiotherapy is ineffective. [12] Gingival overgrowth may be treated with partial gingivectomy. Oral D-penicillamine has been used in some cases. [1] Therapeutic trials with dimethyl sulfoxide, ketotifen, and calcitriol have been given in individual cases. [12] Although the prognosis is better in JHF, the patients are left with deformities and joint contractures.

References
1.
Urbina F, Sazunic I, Murray G.none Infantile systemic hyalinosis or juvenile hyaline fibromatosis? Pediatr Dermatol 2004;21:154-9.
[Google Scholar]
2.
Mancini G, Orange A, Hollander J, Levy M. Fibromatosis, hyalinosis and Stiff Skin syndrome. In: Harper J, Oranje A, Prose N, editors. Textbook of Pediatric Dermatology. 2nd ed. Oxford: Blackwell 2006. p. 951-4.
[Google Scholar]
3.
Gupta LK, Singhi MK, Bansal M, Khullar R, Jain V, Kachhawa D. Juvenile hyaline fibromatosis in siblings. Indian J Dermatol Venereol Leprol 2005;71:115-8.
[Google Scholar]
4.
Nischal KC, Sachdev D, Kharkar V, Mahajan S. Juvenile hyaline fibromatosis. J Postgrad Med 2004;50:125-6.
[Google Scholar]
5.
Finlay AY, Ferguson SD, Holt PJ. Juvenile hyaline fibromatosis. Br J Dermatol 1983;108:609-16.
[Google Scholar]
6.
Burgdorf W, Ruiz-Maldonado R. Benign and malignant tumors. In: Schachner L.A, Hansen R, editors. Pediatric Dermatology. 3 rd ed. Edinburgh: Elsevier Limited; 2003. p. 870.
[Google Scholar]
7.
Larralde M, Santos-Munoz A, Calb I, Magarinos C. Juvenile hyaline fibromatosis. Pediatr Dermatol 2001;18:400-2.
[Google Scholar]
8.
Shin HT, Paller A, Hoganson G, Willner JP, Chang MW, Orlow SJ. Infantile systemic hyalinosis. J Am Acad Dermatol 2004;50:S61-4.
[Google Scholar]
9.
Glover MT, Lake BD, Atherton DJ. Clinical, histologic and ultrastructural findings in two cases of infantile systemic hyalinosis. Pediatr Dermatol 1992;9:255-8.
[Google Scholar]
10.
Huang YC, Xiao YY, Zheng YH, Jang W, Yang YL, Zhu XJ. Infantile systemic hyalinosis: A case report and mutation analysis in a Chinese infant. Br J Dermatol 2007;156:602-4.
[Google Scholar]
11.
Weedon D. Skin Pathology. 2nd Ed. Philadephia: Elsevier; 2002. p. 928
[Google Scholar]
12.
Quintal D, Jackson R. Juvenile hyaline fibromatosis: A 15-year follow-up. Arch Dermatol 1985;121:1062-3.
[Google Scholar]

Fulltext Views
1,495

PDF downloads
1,051
Show Sections