- Juvenile Hyaline Fibromatosis is a genetic disease that causes the formation of soft tissue masses around the body
- The disease occurs due to an autosomal recessive mutation of a gene causing abnormal collections of fibroblasts and excessive collagen VI
- The disease can be classified from mild to life-threatening and currently can only be treated through surgical excision of the masses; however, these masses tend to recur
This case study from the American Journal of case reports outlines the condition of a seven year old girl who presented to Songklanagarind Hospital with multiple soft tissue swellings on her body.
The patient’s medical history reported that she had average developmental growth until the age of 2 years. Since then, multiple soft tissue masses had erupted on her body. The masses grew slowly and were painless. At the time, her parents took her to their local hospital. There, the doctors diagnosed her with leiomyoma, i.e. benign tumors originating from smooth muscle cells. They excised the swellings and followed up with the patient multiple times in a year. However, the swellings reoccurred occasionally on her scalp and forearm, and re-excision was necessary.
The patient was referred to Songklanagarind at the age of seven years. There, doctors discovered the soft tissue swellings on the girl’s ears, forehead, scalp, back, and anterior chest wall. The masses varied from 1-5 cm in diameter, had a well-defined margin and were firm and movable on examination. There was no local inflammation or growth impediment, and organ and cognitive functions were normal. The patient weighed 18.8 kilo grams, with a height of 117 cm on presentation.
The doctors screened the patient with a CT scan, which showed that she had multiple masses of the same type on her scalp. However, the masses did not extend intracranially.
The interdisciplinary team at Songklanagarind decided to manage the patient with mass excision. العاب ماكينات القمار مجانا
An excisional biopsy was performed on the masses, which revealed the presence of benign fibroblastic cells. The immunohistochemistry revealed that the sample was also positive for collagen VI. Furthermore, it was negative for collagen IV which was previously believed to be associated with Juvenile Hyaline Fibromatosis.
Subsequently, the team collected peripheral blood samples from the patient and her parents after obtaining consent. The DNA sequencing revealed a deletion/insertion mutation of the ANTXR2 gene. The mutation, c.1273_1293delinsTCTTG TGGGTTTGGCT occurred in exon 15 of the ANTXR2 gene.
According to the test result, the patient herself had a homozygous inheritance of the deletion/insertion variant. Meanwhile, her parents, who were consanguineous, were heterozygous carriers of the same variant.
The clinical picture and pathological evidence led to the diagnosis of Juvenile Hyaline Fibromatosis.
Juvenile Hyaline Fibromatosis
JHF is an autosomal recessive disorder of unknown prevalence which causes hyaline fibrous tissue growth in various areas of the body, including the skin, bone, and internal organs. A typical presentation includes cutaneous nodules, thicker skin, facial papules, gingival hyperplasia, joint and osteolytic lesions with hyperpigmentation, and organ involvement. The growths are usually present in pediatric patients.
The mutated ANTXR2 genes interrupt the lysosomal degradation of collagen VI, leading to excessive accumulation in the form of hyalinized fibrous nodules. According to previous studies, this fibrosis caused uterine tissue destruction and infertility in mice with ANTXR2 homozygosity. رهان اون لاين Another study showed that the mutated gene indeed caused collagen VI accumulation in human duodenal cells, confirming that the pathology does certainly occur in humans. Although the causative agent (ANTXR2) is known, the pathogenesis of the disease currently remains uncertain
Juvenile Hyaline Fibrosis can be classified into 4 grades:
- Grade 1: Mild – Only skin and gingival involvement
- Grade 2: Moderate – cutaneous + joint and bone involvement (the typical initial presentation)
- Grade 3: Cutaneous + joint and bone + internal organ involvement with or without clinical manifestation (usually manifests as persistent diarrhea or recurrent infection)
- Grade 4: Life threatening
Since the JHF patient at Songklanagarind only clinically manifested with skin lesions, the doctors classified her case as grade 1 JHF.
To date, surgical excision remains the treatment with the best-proven prognosis for juvenile hyaline fibromatosis. However, it is not a complete treatment, as there are chances that the growths recur. Doctors have tried other therapies previously, including penicillamine, methotrexate, and steroid treatments, although none showed definitive curative properties.
Because this disease is genetic, the patient at Songklanagarind and her parents received family planning counseling as part of her treatment.
The authors of the case report explain that molecular genetic testing is a key diagnostic tool for patients with a definitive JHF diagnosis. Therefore, they advocate that it should be a part of every treatment plan. They state that the test helps doctors detect the disease while also allowing them to carry out a risk assessment for family members. The resulting data helps design informed family planning counseling sessions, which are integral for a comprehensive treatment plan.
Choochuen, P., Laochareonsuk, W., Tanaanantarak, P., Kanjanapradit, K., & Sangkhathat, S. (2022). Juvenile Hyaline Fibromatosis: Report of a Case with a Novel ANTXR2 Gene Mutation. ربح حقيقي من الانترنت The American journal of case reports, 23, e935921. https://doi.org/10.12659/AJCR.935921