Cribriform Appearance of White Matter in Canavan Disease Associated with Novel Mutations of ASPA Gene

Cribriform appearance of the brain in Canavan disease is a rare finding. The two presented cases broaden the magnetic resonance imaging (MRI) phenotype wherein numerous oval, cystic structures, a few resembling dilated Virchow-Robin (VR) spaces, were noted in the centrum semiovale, periventricular, and lobar white matter producing a cribriform pattern. Besides, discrete round to oval cysts were present at the gray- white matter junctions in the second case, which were larger and appeared morphologically distinct from the VR spaces. These cysts did not elongate in any plane on imaging and were more representative of giant intramyelinic vacuoles. Genetic analysis revealed novel mutations in the aspartoacylase or ASPA gene that possibly accounts for the severe form of Canavan disease, which probably explains the imaging findings. The multicystic appearance of the white matter in Canavan disease is unusual and possibly represents two different histopathological substrates.

Automated summary

Cribriform appearance of the brain in Canavan disease is rare, with two cases showing multiple oval, cystic structures resembling dilated Virchow-Robin spaces in white matter. Genetic analysis revealed novel mutations in the ASPA gene possibly explaining the severe form of the disease. This multicystic appearance is unusual and may represent two different histopathological substrates.