{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:14:30Z","timestamp":1789942470401,"version":"4.0.1"},"reference-count":13,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,11,1]]},"abstract":"<jats:p>OBJECTIVE. We sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood.<\/jats:p><jats:p>PATIENTS AND METHODS. We report on 3 children who presented in infancy with symptoms and signs that initially were not recognized to be those of systemic hyalinosis. Although the children were evaluated for a variety of problems, including lysosomal storage disorders and nonaccidental trauma, all eventually underwent genetic analysis of the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic hyalinosis.<\/jats:p><jats:p>RESULTS. We describe the recognizable but variable clinical phenotype of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals presented in early infancy with severe pain and progressive contractures. Initial diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case. Although 2 of the children died in infancy as a result of complications of chronic diarrhea, the third child has survived into midchildhood. These data suggest that some ANTRX2 mutations, such as that identified in the long-term survivor, may be associated with a less severe course of disease.<\/jats:p><jats:p>CONCLUSIONS. Although some aspects of systemic hyalinosis may resemble lysosomal storage disorders, the clinical features of systemic hyalinosis are distinctive, and detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of affected individuals should allow for aggressive pain control and expectant management of the multiple associated problems, including gastrointestinal dysfunction.<\/jats:p>","DOI":"10.1542\/peds.2006-0824","type":"journal-article","created":{"date-parts":[[2006,10,17]],"date-time":"2006-10-17T12:08:22Z","timestamp":1161086902000},"page":"e1485-e1492","source":"Crossref","is-referenced-by-count":22,"title":["Systemic Hyalinosis: A Distinctive Early Childhood\u2013Onset Disorder Characterized by Mutations in the Anthrax Toxin Receptor 2 Gene (<i>ANTRX2<\/i>)"],"prefix":"10.1542","volume":"118","author":[{"given":"Joseph T.C.","family":"Shieh","sequence":"first","affiliation":[{"name":"Divisions of Medical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Swidler","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Martignetti","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics"},{"name":"Pediatrics"},{"name":"Oncological Sciences, Mount Sinai School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Celeste M.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imelda","family":"Balboni","sequence":"additional","affiliation":[{"name":"Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Abdul-Rahman","sequence":"additional","affiliation":[{"name":"Divisions of Medical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Enns","sequence":"additional","affiliation":[{"name":"Divisions of Medical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Sandborg","sequence":"additional","affiliation":[{"name":"Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Slavotinek","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Eugene","family":"Hoyme","sequence":"additional","affiliation":[{"name":"Divisions of Medical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2006,11,1]]},"reference":[{"key":"2021120823203178100_R1","doi-asserted-by":"crossref","unstructured":"Bedford CD, Sills JA, Sommelet-Olive D, Boman F, Beltramo F, Cornu G. Juvenile hyaline fibromatosis: a report of two severe cases. J Pediatr.\u20081991;119:404\u2013410","DOI":"10.1016\/S0022-3476(05)82053-0"},{"key":"2021120823203178100_R2","doi-asserted-by":"crossref","unstructured":"Kitano Y, Horiki M, Aoki T, Sagami S. Two cases of juvenile hyalin fibromatosis: some histological, electron microscopic, and tissue culture observations. Arch Dermatol.\u20081972;106:877\u2013883","DOI":"10.1001\/archderm.106.6.877"},{"key":"2021120823203178100_R3","doi-asserted-by":"crossref","unstructured":"Levkoff AH, Gonzalez CG, Neher JL. Congenital diffuse fibromatosis: a case report. 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