Hyperostosis frontalis interna as a novel finding in Unverricht-Lundborg disease

Abstract

Unverricht-Lundborg disease (ULD) is a rare autosomal recessive inherited disorder, which belongs to the progressive myoclonic epilepsies. Genetic linkage studies have indicated that loss-of-function mutations in the cystatin B gene ( CSTB ) lead to the genesis of ULD.1 Even though mutations in CSTB are responsible for ULD, the pathophysiologic role of the CTSB -encoded cystatin B protein is unknown. The cystatin B protein is a cysteine proteinase inhibitor, which protects osteoclasts from experimentally induced apoptosis, and decreases intracellular cathepsin K activity.2 Cathepsin K is expressed predominantly in osteoclasts, and is the major cysteine proteinase involved in bone resorption in rats.3 Overexpression of cathepsin K in mice induces increased thickness and mineral density of diaphyseal cortical bone, and increased porosity of diaphyseal cortex.4 Hyperostosis frontalis interna (HFI) is characterized by a symmetric and nodular thickening of the inner table of the frontal cranial bone. The etiology of the HFI phenotype is obscure, and the lack of evidence of a causative relationship between HFI and clinical findings suggests that it has no pathologic relevance. However, HFI seems to be a …