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.
EPM1 patients exhibited significant thickening in all measured cranial bones compared to healthy controls. The mean skull thickness was 10.0 ¡À 2.0 mm in EPM1 patients and 7.6 ¡À 1.2 mm 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 % ).
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.