OBJECTIVE: Resveratrol is a natural polyphenolic compound with biological activities such as anti-inflammation and antioxidation. Its anti-fibrotic effect has been experimentally demonstrated in the pancreas and liver. This study aims to determine the anti-proliferative effect of resveratrol on fibroblasts obtained from hyperplastic gingival tissues from a patient diagnosed with Juvenile Hyaline Fibromatosis (JHF).
METHODS: Primary gingival fibroblast cell lines were obtained from gingival growth tissues by the gingivectomy of a patient with JHF. Gingival fibroblasts were treated with or without 3 different doses of resveratrol (50, 100, 200 µM). Cytotoxicity and cell proliferation were evaluated after 24, 48, and 72 h. Collagen, TGF, and CTGF were analyzed by ELISA in the 48-hour supernatants.
RESULTS: All three doses of resveratrol suppressed the proliferation of JHF gingival fibroblasts at 24 and 48 h without showing any cytotoxic effect compared to the control group (p < 0.0001). At 72 h, 100 and 200 µM resveratrol showed significantly less proliferation (p < 0.0001), less collagen, CTGF, and TGF- β (p < 0.001) than the control group.
CONCLUSIONS: Resveratrol had a profound anti-proliferative effect on gingival fibroblasts obtained from gingival enlargements with JHF, suggesting that it can be used as a therapeutic to prevent excessive cell growth by suppressing collagen, CTGF, and TGF- β synthesis in the pathogenesis of hyperplasia.

A rare autosomal recessive condition called infantile systemic hyalinosis (ISH) is characterized by early-onset skin lesions that progress to the formation of numerous contractures. The underlying disease is the progressive accumulation of hyaline substances in many tissues. We are presenting the case of a male infant who was referred for evaluation and management at the age of six months. The infant had a history of recurrent episodes of diarrhea and showed limited movement in all four limbs. Upon physical examination, hyperpigmented papulonodular lesions on bony prominences and perianal regions were found, coupled with contractures in the elbow and knee joints. Hyaline deposition in the mid-dermal region was confirmed by histopathological analysis of a skin biopsy sample. The baby also had acute otitis media, which needed to be treated with antibiotics. Parents were counseled regarding the disease\'s diagnosis, complications, prognosis, and inheritance pattern. This case highlights the clinical presentation, diagnostic process, and management strategies employed in the care of ISH, emphasizing the importance of early recognition and multidisciplinary management in mitigating its devastating effects.

BACKGROUND: Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey.
METHODS: Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser.
RESULTS: Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years.
CONCLUSIONS: HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.

Hyaline fibromatosis syndrome is an extremely rare autosomal recessive condition caused by biallelic pathogenic variants in the ANTXR2 gene that leads to abnormal growth of hyalinized fibrous tissue. Severity ranges from life-threatening intractable diarrhea, recurrent infection, and acute pain to milder disease resulting in skin lesions and less severe contractures. Here, we report the case of a 3-month-old female who presented with joint contractures and severe pain followed by failure to thrive. Diagnosis via ultra-rapid whole genome sequencing allowed our team to provide appropriate care and anticipatory guidance for this patient and family.

Juvenile hyaline fibromatosis (JHF) is a rare, hereditary disease characterized by abnormal hyaline deposits within the skin, soft tissues, joints, and bones. The condition itself is often debilitating, with no curative treatment available. A definitive diagnosis is established by genetic testing. However, the hallmarks of gingival hypertrophy, subcutaneous scalp nodules, and joint contractures can be used as a clinical guide when genetic testing is unavailable. Here, we report an unusual case of a five-year-old child clinically diagnosed with juvenile hyaline fibromatosis with atypical nodules exclusively confined to the perioral region.

This case report was written with the assistance of the large language model known as ChatGPT, a form of generative artificial intelligence that can write grammatically correct and semantically meaningful prose on a multitude of topics. Here, it has assisted us in presenting a case of anesthetic management for a case of Juvenile Hyaline Fibromatosis (JHF), an extremely rare genetic disorder that is part of a spectrum of diseases presently characterized as Hyaline Fibromatosis Syndrome (HFS), which also includes a more severe variant presenting in infancy. HFS is caused by autosomal recessive mutations in the ANTXR2 (anthrax toxin receptor cell adhesion molecule 2) gene, which binds collagen IV and laminin, suggesting that it may be involved in extracellular matrix adhesion. Defects in this molecule lead to abnormal deposition of hyaline material in perivascular areas, presenting as cutaneous lesions, joint contractures, and in some cases internal organ dysfunction. Anesthetic management of patients with JHF may present difficulties with patient positioning and airway management. Most reports of anesthetic management concern children with severe disease and adult reports are uncommon. We present a case of JHF in a 39-year-old woman managed for resection of a lower extremity cutaneous lesion. The anesthetic management of this relatively minor case was uneventful, but the process of drafting this report with the assistance of the new software tool ChatGPT was informative of both its strengths and limitations.

Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISF) are rare progressive, fatal autosomal recessive fibromatosis disorders that are characterized by the deposition of hyaline in various tissues. Mutations in capillary morphogenesis gene 2 are responsible for both of these conditions. These disorders usually present with fleshy, papular lesions, joint contractures, gingival hyperplasia, and persistent diarrhoea. An 18-month-old boy presented with multiple scalp abscesses, facial nodules, gingival hypertrophy, hypertrophic verrucous plaques and joint contractures with unique dermoscopic features and a history of recurrent diarrhoea and infections. Histopathological examination following skin biopsy revealed deposition of hyaline in the stroma and subcutaneous tissues. JHF is a differential diagnosis in children who present with multiple scalp nodules. Here, we report the case of overlapping features of JHF and ISH. The evolution of this case provides a special opportunity to further understand the pathogenesis and clinical characterization of hyaline fibromatosis syndrome.

Hyaline fibromatosis syndrome is a rare autosomal recessive disorder with ANTXR2 mutations characterised by the accumulation of hyaline substances in tissues. We present a case with the severe form-infantile systemic hyalinosis (ISH)-with long survival and review the literature.
Trio-exome sequencing revealed compound heterozygous mutations, including a novel 4.41 kb deletion on 4q21.21 and the previously reported c.1294C > T mutation, in the ANTXR2 gene. He was diagnosed with ISH and treated symptomatically. After follow-ups until 4 years of age, his recurrent respiratory infections and diarrhoea improved after one severe diarrhoea attack treated with intravenous gamma globulin. He is now awaiting surgical excision of gingival hypertrophy and joint contractures.
The novel gross deletion in ANTXR2 enriches the genetic mutation spectrum of hyaline fibromatosis syndrome. The manifestation of decreased foetal movement, acute-infection attack or intravenous gamma globulin treatment may be associated with hyaline fibromatosis syndrome. A review of 116 reported cases reveals that missense mutations in the vWA domain are associated with joint symptoms, respiratory tract infection and diarrhoea, while frameshift mutations are associated with facial deformities and speech delays. We have enriched the current knowledge of the clinical manifestations and genetic mutation spectrum of HFS.

BACKGROUND: Juvenile hyaline fibromatosis (JHF) is a rare genetic condition characterized by impaired collagen production or metabolism. This study aims to present a rare case of JHF.
METHODS: An 11-year-old boy presented with bilateral keloid-like lesions on his ears and admitted intermittent reappearance of such lesions since he was seven. He was born to second-degree relative consanguineous parents. Physical examination revealed bilateral soft pink masses on the ears, multiple scars on the scalp, severe gingival hypertrophy, multiple small soft white papules on the anterior neck, broadly shaped enlargements on the ends of the fingers and toes, and multiple reticulated hard livedoid and hyperpigmented macules on the back and anterior lower extremities. A 5 mm biopsy was taken from the lesion on the ear and histopathological examination of the specimen revealed a normal epidermis but dermal and subcutaneous deposits of nodules composed of abundant amorphous eosinophilic hyaline material with sparse embedded fibroblast associated with areas of congestion and focal hemorrhage. The ear lesions were managed by surgical excision with intraregional steroid injections to prevent relapse. To improve eating ability and oral hygiene, a gingivectomy was planned.
CONCLUSIONS: JHF presents with bone lesions, gingival hypertrophy, joint contractures, and skin lesions. The clinical features usually appear late in infancy and up to 5 years. The condition occurs mostly sporadically. A portion of the cases can be in siblings born to consanguineous parents.
CONCLUSIONS: JHF is a rare genetic disorder that can present even beyond five years. There is no standard treatment for these cases.

Juvenile hyaline fibromatosis (JHF) is an extremely rare autosomal recessive disease that typically presents in infancy or early childhood. Largely due to the rarity, JHF is still not widely recognized by clinicians and pathologists in China. It is not uncommonly to misdiagnose the disease as other types of disorders. In this study, we present our experience with five cases of JHF to enhance the recognition of this rare but distinctive entity. There were 4 males and 1 female, with age at presentation ranging from 5 to 44 years. All patients presented with multiple subcutaneous nodular lesions of varying size in various parts of the body since birth or early childhood. Three patients also had joint involvement. Pathologically, the lesions were poorly circumscribed, located mainly in the dermis and subcutis. All five cases were characterized by abundant homogeneous hyaline-like matrix that differs sharply from the adjacent connective tissue, which stained strongly with periodic acid-Schiff (PAS) and was diastase resistant. Embedded within the eosinophilic glassy matrix were cords or small clusters of plump spindled to epithelioid cells, frequently with clear cytoplasm. Familiarity with the characteristic features of JHF is not only important in avoiding misdiagnosis but also essential for clinical management and prognostic evaluation.