TY - JOUR
T1 - Systemic hyalinosis
T2 - A distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (ANTRX2)
AU - Shieh, Joseph T.C.
AU - Swidler, Petra
AU - Martignetti, John A.
AU - Ramirez, Maria Celeste M.
AU - Balboni, Imelda
AU - Kaplan, Julie
AU - Kennedy, Jeanette
AU - Abdul-Rahman, Omar
AU - Enns, Gregory M.
AU - Sandborg, Christy
AU - Slavotinek, Anne
AU - Hoyme, H. Eugene
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Anthrax toxin receptor 2 gene
KW - Chronic pain
KW - Fibromatosis
KW - Genetic testing
KW - Gingival hypertrophy
KW - Hyalinosis
KW - Progressive childhood contractures
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U2 - 10.1542/peds.2006-0824
DO - 10.1542/peds.2006-0824
M3 - Article
C2 - 17043134
AN - SCOPUS:33750933539
SN - 0031-4005
VL - 118
SP - e1485-e1492
JO - Pediatrics
JF - Pediatrics
IS - 5
ER -