infantile systemic hyalinosis and juvenile hyaline fibromatosis are very rare hereditary disorders which usually occur in arabs and exceedingly rare in indians .
hyaline fibromatosis syndrome ( hfs , online mendelian inheritance in man 228600 ) is a rare autosomal recessive condition characterized by deposition of amorphous , hyaline material in skin and visceral organs .
infantile systemic hyalinosis ( ish ) and juvenile hyaline fibromatosis ( jhf ) are two variants of hfs .
ish is distinguished from jhf by hyaline deposits in multiple organs , recurrent infections , and death within the first 2 years of life .
a 2.5-year - old female patient born of second - degree consanguineous marriage and normal full - term vaginal delivery presented with four painless swellings over scalp of 6 months duration slowly increasing in size along with raised lesions over face and perianal region of 5 months duration increasing in number .
she had fever , cough , and cold for 6 days duration with history of recurrent hospital admissions in the past for bronchopneumonia and diarrhea .
her mother gave a history of inability to move limbs over the past 1 year and inability to stand and walk till date .
there was no similar history in siblings , parents , or other family members . on examination , four bilateral , nontender , and mobile swellings of sizes ranging from 4 cm  5 cm to 7 cm
face showed depressed nasal bridge with multiple 15 mm asymptomatic nontender skin colored to pink papules clustered over bilateral nasolabial folds , nose , perioral area , eyebrows , and pinna [ figure 2 ] .
similar multiple , tiny , shiny , pink , moist papules were seen around anal orifice . a pink , fleshy , linear plaque of size 15
polydactyly was present in the left hand with hyperpigmented indurated plaques over bilateral elbows , knees , and knuckles [ figure 4a  c ] .
flexion contractures of elbow and knee joints leading to a frog - like position were noticed [ figure 1a ] .
four bilateral , nontender , mobile cystic swellings of sizes ranging from 4 cm  5 cm to 7 cm  6 cm were seen over scalp ( a and b ) .
surface of one swelling showed hemorrhagic crusting and bleeding ( c ) face showed depressed nasal bridge with multiple 15 mm asymptomatic non - tender skin coloured to pink papules clustered over bilateral nasolabial folds , nose , perioral area , eyebrows ( a ) and pinna ( b , c ) multiple , tiny , shiny , pink , moist papules seen around anal orifice ( a , b ) .
a pink fleshy linear plaque of about 15 cm was seen in natal cleft and lower back ( a ) polydactyly was present in the left hand with hyperpigmented indurated plaques over bilateral elbows , knees and knuckles ( a - c ) .
dental examination showed nodular gum hyperplasia ( d ) a differential diagnosis of deposition disorder , hyalinosis , and stiff skin syndrome was proposed .
complete blood count showed hemoglobin ( 8 g / dl ) , total leukocyte count of 15,200/mm mean corpuscular volume , and decreased mean corpuscular hemoglobin ( mch ) concentration and mch whereas peripheral blood smear revealed microcytic hypochromic anemia .
ultrasound of the skull showed superficial fluid filled lesions with no communication with inner side of the skull .
histopathological examination of papule from perianal region showed thickened dermis with abundant hyalinized eosinophilic ground substance [ figure 5a ] .
higher magnification ( 400 ) showed a few spindle cells in abundant hyalinized eosinophilic ground substance with chondroid appearance at few places [ figure 5b ] .
stain [ figure 6 ] but was negative with alcian blue or masson 's trichrome stains , thereby ruling out mucopolysaccharidosis and collagen deposition disorder , respectively .
patient was advised physiotherapy for release of contractures and surgical excision of scalp tumors under care of pediatric surgeon .
( a ) thickened dermis with abundant hyalinized eosinophilic ground substance ( h and e , 100 ) .
( b ) few spindle cells in abundant hyalinized eosinophilic ground substance with chondroid appearance at few places ( h and e , 400 ) hyaline material stained magenta pink ( periodic acid 
hfs ( online mendelian inheritance in man 228600 ) is a rare autosomal recessive condition caused by homozygous or compound heterozygous mutation in the gene encoding capillary morphogenesis protein-2 ( cmg2 or antxr2 ) on chromosome 4q21 .
most frequent in arab with around < 70 cases of jhf and < 20 cases of ish were reported worldwide till date .
recent research suggests focal synthesis of glycosaminoglycan and hyaluronic acid . recently , absent pro - alpha2 collagen chain and an absent collagen type 3 along with increased synthesis and decreased degradation of type 1 collagen have been suggested .
abnormalities begin in the first few months of life with progressive flexor joint contractures causing a frog - like position and inability to stand and walk .
face shows peculiar features such as deep set eyes , depressed nasal bridge , square box head , and prominent forehead .
characteristic skin lesions are papulonodular skin lesions , gingival hypertrophy , and thickened hyperpigmented macules / patches over bony prominences of the joints .
radiological examination of the long bones may show delayed skeletal maturation , severe osteopenia , bony erosions , and lucent defects .
ish is distinguished from jhf by hyaline deposits in multiple organs , recurrent infections , protein - losing enteropathy , failure to thrive , and death within the first 3 years of life recurrent chest infections being the leading cause of death .
hypochromic microcytic anemia , low albumin , moderately elevated white blood cells count , and platelet count may be present .
clinical differentials include congenital generalized fibromatosis , nodular amyloidosis , faber 's disease , winchester disease , mucopolysaccharidosis neurofibromatosis , neonatal onset multisystem inflammatory disease ( nomid ) . histopathology or electron microscopy of skin tissue is needed to establish the diagnosis .
histopathological examination of a typical papulonodular skin lesion shows deposition of an amorphous hyaline , eosinophilic substance in which spindle - shaped cells are embedded
the material is pas positive and diastase resistant and does not stain with alcian blue .
early surgical excision is recommended by few authors to prevent new lesions in jhf , but recurrences are frequent .
genetic counseling includes informing the parents that at conception next child has a 25% chance of being affected .
the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )
has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .
the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .
hfs is a relatively new term coined recently to include cases of ish , jhf , and intermediate cases with overlapping features of both .
the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )
has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .
the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .
hfs is a relatively new term coined recently to include cases of ish , jhf , and intermediate cases with overlapping features of both .
the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s )
has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal .
the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .
hfs is a relatively new term coined recently to include cases of ish , jhf , and intermediate cases with overlapping features of both .
 hyaline fibromatosis syndrome ( hfs ) is rare autosomal recessive disease characterized by the deposition of amorphous hyaline material in skin and visceral organs . 
 it represents a disease spectrum with infantile systemic hyalinosis ( ish ) being the severe form and juvenile hyaline fibromatosis ( jhf ) being the mild form . 
 dermatologic manifestations include thickened skin , perianal nodules , and facial papules , gingival hyperplasia , large subcutaneous tumors on the scalp , hyperpigmented plaques over the metacarpophalangeal joints and malleoli , and joint contractures . 
 ish shows a severe visceral involvement , recurrent infections , and early death . 
 we report a case of 2.5-year - old female patient who presented with hfs who had overlapping features of both ish and jhf . to the best of our knowledge , 
 very few cases of hfs have been reported in indian literature till date . 
Introduction
Case Report
Discussion
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