Published online October 16, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. e1485-e1492 (doi:10.1542/peds.2006-0824)

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shieh, J. T.C. Articles by Hoyme, H. E. Search for Related Content PubMed PubMed Citation Articles by Shieh, J. T.C. Articles by Hoyme, H. E. Related Collections Genetics & Dysmorphology Social Bookmarking                         What's this?

ARTICLE

Systemic Hyalinosis: A Distinctive Early Childhood–Onset Disorder Characterized by Mutations in the Anthrax Toxin Receptor 2 Gene (ANTRX2)

Joseph T.C. Shieh, MD, PhD^a, Petra Swidler, MD^c, John A. Martignetti, MD, PhD^d,e,f, Maria Celeste M. Ramirez, BS^d, Imelda Balboni, MD, PhD^b, Julie Kaplan, MD^c, Jeanette Kennedy, RN, MS^b, Omar Abdul-Rahman, MD^a, Gregory M. Enns, MB, ChB^a, Christy Sandborg, MD^b, Anne Slavotinek, MBBS, PhD^c and H. Eugene Hoyme, MD^a

^a Divisions of Medical Genetics
^b Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California
^c Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, California
^d Departments of Human Genetics
^e Pediatrics
^f Oncological Sciences, Mount Sinai School of Medicine, New York, New York

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.

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.

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.

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.

---

Key Words: hyalinosis • chronic pain • progressive childhood contractures • gingival hypertrophy • anthrax toxin receptor 2 gene • genetic testing • fibromatosis

Abbreviations: ANTRX2—anthrax toxin receptor 2 gene

---

Accepted May 24, 2006.

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?