title: Thickened skull, scoliosis and other skeletal findings in Unverricht-Lundborg disease link cystatin B function to bone metabolism.
abstract: OBJECTIVE
  Unverricht-Lundborg disease (EPM1) is a rare type of inherited progressive myoclonic epilepsy resulting from mutations in the cystatin B gene, CSTB, which encodes a cysteine cathepsin inhibitor. Cystatin B, cathepsin K, and altered osteoclast bone resorption activity are interconnected in vitro. This study evaluated the skeletal characteristics of patients with EPM1.
  
  
  METHODS
  Sixty-six genetically verified EPM1 patients and 50 healthy controls underwent head MRI. Skull dimensions and regional calvarial thickness was measured perpendicular to each calvarial bone from T1-weighted 3-dimensional images using multiple planar reconstruction tools. All clinical X-ray files of EPM1 patients were collected and reviewed by an experienced radiologist. A total of 337 X-ray studies were analyzed, and non-traumatic structural anomalies, dysplasias and deformities were registered.
  
  
  RESULTS
  EPM1 patients exhibited significant thickening in all measured cranial bones compared to healthy controls. The mean skull thickness was 10.0±2.0mm in EPM1 patients and 7.6±1.2mm in healthy controls (p<0.001). The difference was evident in all age groups and was not explained by former phenytoin use. Observed abnormalities in other skeletal structures in EPM1 patients included thoracic scoliosis (35% of EPM1 patients) and lumbar spine scoliosis (35%), large paranasal sinuses (27%), accessory ossicles of the foot, and arachnodactyly (18%).
  
  
  CONCLUSIONS
  Skull thickening and an increased prevalence of abnormal findings in skeletal radiographs of patients with EPM1 suggest that this condition is connected to defective cystatin B function. These findings further emphasize the role of cystatin B in bone metabolism in humans.
authors.affiliation: Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Suoranta
authors.forename: Hannu
authors.initials: H
authors.lastname: Manninen
authors.forename: Päivi
authors.initials: P
authors.lastname: Koskenkorva
authors.forename: Mervi
authors.initials: M
authors.lastname: Könönen
authors.forename: Rita
authors.initials: R
authors.lastname: Laitinen
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Reetta
authors.initials: R
authors.lastname: Kälviäinen
authors.forename: Ritva
authors.initials: R
authors.lastname: Vanninen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D055313:Cystatin B / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012600:Scoliosis / Q000378:metabolism* / Q000473:pathology*; D012886:Skull / Q000378:metabolism* / Q000473:pathology*; D020194:Unverricht-Lundborg Syndrome / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D055313:Cystatin B