CANDLE syndrome is caused by mutations in PSMB8, a gene recently reported to cause "JMP" syndrome (joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced childhood-onset lipodystrophy) in adults.
Skeletal abnormalities (for MPS IVA and MPS VI), joint contractures (for MPS II), and typical facial features (for MPS I) were the most frequently reported first signs/symptoms.
The present study demonstrates the important role of HIF-1 in the initial progression of immobilization-induced joint contracture, and indicates the possibility of molecular treatment to prevent the progression of joint contracture prior to intervention with physical therapy.
Further, the evidence of TGF β2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies.
Skeletal abnormalities (for MPS IVA and MPS VI), joint contractures (for MPS II), and typical facial features (for MPS I) were the most frequently reported first signs/symptoms.