Heterozygous Mutations in ANTXR2 Gene in a Child with Oral Manifestations of Hyaline Fibromatosis Syndrome: A Case Report and Review of Phenotype-Genotype Correlations

Abstract

<h3>Introduction</h3> Hyaline fibromatosis syndrome (HFS) is an autosomal recessive condition with hyaline deposits in the oral mucosa, skin, and other tissues, causing severe deformity and disability. HFS is caused by homozygous and compound heterozygous mutations in the <i>ANTXR2</i> gene. <i>ANTXR2</i>is ubiquitously expressed in all tissues except for the brain, and mutations in this gene are responsible for the complex clinical manifestations of this condition. Clinical hallmarks of the syndrome include progressive joint contractures, gingival hypertrophy, skin nodules, perianal masses, and hyperpigmentation over bony prominences. <h3>Case Findings</h3> A 19 month old female diagnosed with HFS, heterozygous for two novel pathogenic mutations in two separate alleles in <i>ANTXR2</i>, was evaluated for gingival hypertrophy. Additional clinical findings included subcutaneous nodularity of her facial skin, ears, lip commissures and with joint contractures. Rapid gingival overgrowth obscuring the primary dentition over five months, as well as involvement of her facial skin and perianal region necessitated multidisciplinary treatment to debulk the fibromatoses. <h3>Results</h3> A gingivectomy was performed to expose the patient's erupted primary dentition to facilitate oral mastication and potential for speech and language development. A preauricular nodule and perianal mass were excised. The histopathology of the gingival, preauricular, and perianal lesions revealed characteristic diffuse vascular hyaline collagen, typical for the syndrome. <h3>Conclusion</h3> Hyaline fibromatosis syndrome is rare and has significant oral manifestations. The histopathology of lesional tissues are quite characteristic. The novel mutations discovered in our patient and the clinical presentation support the phenotype-genotype correlations that have been previously suggested. The clinical phenotype coupled with the genotypic findings would classify this case as Grade 3 (severe) using a proposed four tier grading system for HFS. The differential diagnosis for progressive gingival overgrowth in children should include hyaline fibromatosis syndrome, as gingival hyperplasia and subcutaneous nodules may be the initial presentation in milder cases.