|Year : 2019 | Volume
| Issue : 1 | Page : 64-67
Hyaline fibromatoses syndrome: A rare entity
Resham Vasani, Deepak Parikh
Department of Pediatric Dermatology, Bai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India
|Date of Web Publication||14-Dec-2018|
Dr. Resham Vasani
C-1, 22, Karmakshetra, Near Shanmukhananda Hall, Sion, Mumbai - 400 037, Maharashtra
Source of Support: None, Conflict of Interest: None
Hyaline fibromatoses syndrome is a rare autosomal recessive disorder with very few cases reported from India till date. It is characterized by the deposition of amorphous hyaline material in the skin, bones, and viscera. It represents a disease spectrum with infantile systemic hyalinosis as the most severe form and juvenile hyaline fibromatoses (JHF) being the mild form. These conditions characteristically present with overlapping clinical features such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. Identification of this condition by the treating dermatologist is important to facilitate an early diagnosis and a multidisciplinary follow-up. We report one such case of this uncommon condition– JHF.
Keywords: Hyaline Fibromatoses Syndrome, Juvenile Hyaline Fibromatoses, Infantile systemic hyalinosis
|How to cite this article:|
Vasani R, Parikh D. Hyaline fibromatoses syndrome: A rare entity. Indian J Paediatr Dermatol 2019;20:64-7
| Introduction|| |
Hyaline fibromatoses syndrome (HFS) requires a multidisciplinary approach; however, the role of a dermatologist is crucial to identify its cutaneous features and thereby facilitating early diagnosis and later, surgical intervention, genetic counseling for the family, and a multidisciplinary follow-up. There are only a few cases reported from India till date.,, We report one more case of this rare condition.
| Case Report|| |
A 15-month-old male child was referred to us by the neurology department for a rash on the forehead, perinasal, perioral areas, and neck. He was being evaluated for decreased limb movements. The index case was the second child, born of third-degree consanguineous marriage, at term, through a cesearean section, and cried immediately after birth. The perinatal period was uneventful. The parents started noticing progressive tightening of the skin over the extremities of the child with decreased limb movements. No associated systemic comorbidities have been detected till date. There was no similar history in the 9-year-old sibling, in the parents or the other family members. The child started neck holding at 1 year and sitting with support at 8–9 months. Unidextrous grasp was present. Social milestones achieved included maintaining eye contact, recognition of parents, response to name, separation anxiety, understanding peek-a-boo, and “bye-bye.”
The child weighed 5.7 kg with a head circumference of 45 cm suggestive of macrocephaly. There was no regional lymphadenopathy. There were flexion contractures over the elbows, knees, and small joints of the fingers leading to a frog-like position [Figure 1]. The forehead was prominent with depressed nasal bridge and excessive facial hair [Figure 2]a. There were multiple asymptomatic nontender skin-colored to pink, pinhead-sized papules clustered on the forehead along the eyebrows, bilateral nasolabial folds, perioral area, and pinnae [Figure 2]b. The papules coalesced to form moist pink plaques on the neck, retroauricular area and in a linear distribution along the natal cleft [Figure 2]c. Multiple, shiny, and moist papulonodular lesions were present around the anal orifice [Figure 3]. Hyperpigmented indurated plaques were present on the bony prominences of the elbow, knees, wrist, and ankle joints [Figure 4]. Palms and soles showed normal dermatoglyphics. Eye and ear examination were normal. Dental examination was normal. Power was >3/5 at the hip joint and 2/5 at the elbow and shoulder joints bilaterally.
|Figure 1: Flexion contractures of the elbows, knees, and small joints of the hands and feet giving a frog-like position|
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|Figure 2: (a) Prominent forehead with depressed nasal bridge with the presence of multiple pink, pinhead-sized papules clustered on the forehead along the eyebrows, bilateral nasolabial folds, and perioral area. (b) Coalescence of papules seen on the neck. (c) Coalescence of papules in a linear distribution to form a plaque along the natal cleft|
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|Figure 3: Multiple, shiny, and moist papulonodular lesions present around the anal orifice|
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|Figure 4: (a) Hyperpigmented indurated plaques on the ankle. (b) Hyperpigmented indurated plaques on the wrist joint|
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Hematological investigations revealed hypochromic microcytic anemia (Hb-8.4% gm) leukocytosis (white blood cell [WBC]-20.31 × 103/μl), with thrombocytosis (Platelet count – 756 × 103/μl). The ultrasound of the abdomen, two-dimensional echo, and X-ray chest were normal. Skeletal survey showed thinning of cortex and rarefaction [Figure 5].
Histopathology of the papular eruption from the forehead showed a thinned out epidermis with the presence of periodic acid–Schiff (PAS)-positive diastase resistant eosinophilic hyaline material deposited in the upper dermis and the adnexal structures [Figure 6]. This confirmed the final diagnosis as HFS. As per the grading system proposed by Nofal et al., this patient had moderate severity on account of lack of evident internal organ involvement and absence of severe clinical decompensation.
|Figure 6: Thinned out epidermis with the presence of eosinophilic hyaline material present in the upper dermis (H and E, ×10)|
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The patient was advised physiotherapy for the release of contractures. Genetic counseling of parents is planned since there is a 25% chance of the next child being similarly afflicted.
| Discussion|| |
HFS is a rare autosomal recessive disorder, caused by homozygous mutation or compound heterozygous mutation in gene encoding for capillary morphogenesis protein-2 also called as anthrax toxin receptor-2 on chromosome 4q21.
These mutations account for possible absence of pro α2 collagen chains and Type III collagen with increased synthesis and decreased degradation of type I collagen, which is hypothesized to be the origin of hyaline material that gets deposited in the papillary and reticular dermis and leads to the formation of papules or nodules. It can compromise specific functions when deposited in various organs.
Infantile systemic hyalinosis (ISH) and juvenile hyaline fibromatoses (JHF) are two variants of HFS, with molecular defect common to both diseases expressing genotypic and phenotypic variables consequent to different possible mutations of the same gene. Both diagnoses should be considered in children presenting with clinical manifestations such as nodules and or pearly papules, gingival hyperplasia, and joint contractures. ISH is differentiated from JHF by hyaline deposits in multiple organs, recurrent infections, protein-losing enteropathy, failure to thrive, and death.
These children are usually normal at birth. The sequence and severity of organ involvement is variable. Progressive flexion contractures are the most debilitating problem causing a frog-like position with inability to stand and walk. The facial features comprise deep-set eyes, depressed nasal bridge, prominent forehead, and macrocephaly. Skin lesions are the most common feature. Skin tumors associated with JHF are divided into three types. (a) Small fleshy pearly papules, especially in nasolabial folds, mastoid area, and neck. (b) Translucent nodules on pulps of fingers, external portions of ears, and nose. (c) Large subcutaneous tumors, especially on the scalp and also on the trunk and extremities. Gingival hyperplasia can lead to poor oral hygiene, the inability to feed, and dental infections. Thickened hyperpigmented macules and plaques over bony prominences of joints may be seen.
Radiological changes include delayed skeletal maturation, severe osteopenia, bony erosions, and lucent defects. Hematological changes include low serum albumin, hypochromic, and microcytic anemia, with moderately elevated WBC count and elevated platelet count.
Histopathology reveals the deposition of amorphous hyaline eosinophilic substance, in which spindle-shaped cells are embedded. It has been described to have a chondroid appearance and is PAS positive and diastase resistant.
Differential diagnosis of this condition include congenital generalized myofibromatosis, Farbers lipogranulomatosis, lipoid proteinosis, mucopolysaccharidosis, and Winchester syndrome that can be differentiated on the basis of clinical, histological, and biochemical criteria. [Table 1] describes the salient features of these differentials.
The treatment is mainly palliative. Intralesional steroids have been used to reduce the size of the lesions in early stages. Early surgical excision has been recommended to prevent new lesions, but recurrences are frequent. Capsulotomy has been shown to provide some relief. Radiotherapy is ineffective. Physiotherapy is advocated for muscle strengthening and treating contractures. Penicillamine, methotrexate, calcitriol, dimethylsulfoxide, and ketotifen have been tried in isolated cases with limited success. Partial or radical gingivectomy with extraction of decayed or unstable teeth is said to be helpful. Treatment of infections is essential. Proteasome and possibly other components of endoplasmic reticulum degradation system are potential targets for treatment of HFS.
Declaration of patient consent
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 cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]