Hyaline fibromatosis syndrome (HFS) is an autosomal recessive disorder caused by variants in the ANTXR2 gene. Clinically, HFS is characterized by papular and nodular skin lesions, gingival hyperplasia, joint contractures, and bone involvement in variable degrees. In this report, we present a 3-year-old Syrian boy with HFS, detailing his clinical and genetic profile, furthering the understanding of genotype-phenotype correlation in the ANTXR2 gene and HFS.

Hyaline fibromatosis syndrome (HFS) is a rare genetic disorder encompassing juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH), caused by mutations in the anthrax toxin receptor 2 gene (ANTXR2). This condition leads to the accumulation of hyaline plaques in the skin and organs, resulting in symptoms such as skin lesions, joint contractures, and digestive issues, often culminating in early mortality due to infections or diarrhea. By 2005, 20 mutations in ANTXR2 linked to ISH and JHF had been documented, impairing cellular adhesion to the laminin matrix. In this study, we present a case of a 6-month-old Iranian female of western Asian ethnicity, born to consanguineous parents. She exhibited hyperpigmentation of the proximal interphalangeal (PIP) joints, knee flexion contractures, persistent diarrhea, and failure to thrive. Initial assessments suggested arthrogryposis; however, the presence of hyperpigmented nodules and perianal plaques prompted further investigation. Genetic analysis confirmed a homozygous mutation in ANTXR2 and incidental heterozygous mutations in the HEXA and PAH genes. The patient will undergo regular monitoring and may require immunosuppressive therapy and orthopedic interventions. Hyaline fibromatosis syndrome presents unique diagnostic challenges due to its overlap with other conditions like arthrogryposis. While arthrogryposis typically lacks systemic symptoms, HFS is marked by significant pain and systemic manifestations due to hyaline deposits in tissues. The case presented aligns with existing literature regarding HFS characteristics, including joint contractures and skin lesions. The identification of the c.697+1G>A mutation at a splice site within the ANTXR2 gene highlights potential mechanisms contributing to HFS pathology. This finding emphasizes the necessity for comprehensive genetic profiling when diagnosing rare syndromes. Furthermore, low allele frequencies of this variant across population databases underscore its rarity and potential significance in disease manifestation. Hyaline fibromatosis syndrome (HFS) is an uncommon autosomal recessive disorder that is marked by notable clinical features, such as the deposition of hyaline material in various tissues, joint contractures, and systemic complications. The case discussed illustrates the diagnostic challenges associated with HFS, particularly in a young patient who presented with atypical symptoms that initially indicated arthrogryposis. Genetic analysis revealed a homozygous mutation in the ANTXR2 gene, specifically the c.697+1G>A variant, which interferes with normal splicing and results in the absence of functional protein. This observation emphasizes the critical role of genetic testing in the precise diagnosis of rare syndromes and in differentiating them from other hereditary disorders.

This case report presents a 5-year-old boy diagnosed with juvenile hyaline fibromatosis (JHF), an extremely rare autosomal recessive disorder characterized by the abnormal accumulation of collagen. The patient exhibited a recurrent giant subcutaneous tumor measuring 20 cm in diameter, along with multiple tumors in the oral cavity, gingiva, and joints, leading to significant facial deformity and functional impairments. Previous surgeries at ages 1 and 2 for tumor removal resulted in recurrence. Surgical intervention was performed to excise the large tumor and alleviate symptoms. Pathologic analysis confirmed the diagnosis of JHF. This case highlights the challenges in managing JHF and the need for multidisciplinary approaches in treatment.

Hyaline fibromatosis syndrome (HFS) is a rare, autosomally-recesfvsive disease characterized by papulonodular skin lesions, soft tissue masses, joint contractures, gingival overgrowth, and osteolytic bone lesions. Mutations in capillary morphogenesis gene 2 are responsible for both these conditions. Generally, an autosomal recessive pattern is assumed to be the most common mode of inheritance. Here, we report an unusual case of a twenty-three-year-old female patient with HFS who reported with a chief complaint of growing nasal mass for three months. There was no history of pain or bleeding associated with the nasal mass. Due to the growing mass, she experienced right nasal obstruction, which compromised her quality of life. There was an unremarkable family history. Her physical examination revealed multiple asymptomatic pinkish-white papulonodular lesions located at multiple sites. Intra orally, she had generalized gingival enlargement. Her nasal examination revealed a right sided nasal mass, bright red in color. The lesion was soft on palpation. All the results of hematological and biochemical tests were normal. However, skeletal radiographic examination showed the joint contractures on her knees and elbows without the presence of osteolytic bone lesions. The nasal lesion was surgically excised and histopathological examination revealed features suggestive of HFS.