General description

Leukoencephalopathy with calcification and cysts (LCC), also known as Labrune syndrome, is a rare, autosomal recessive genetic disorder characterized by a triad of neuroimaging findings: diffuse and asymmetric leukoencephalopathy, extensive cerebral calcifications, and parenchymal brain cysts. This triad reflects an underlying cerebral microangiopathy, a disease of the small blood vessels in the brain. LCC is caused by biallelic mutations in the SNORD118 gene, located on chromosome 17p13.1. This gene encodes a small nucleolar RNA, though the precise mechanism by which SNORD118 mutations lead to the LCC phenotype remains an area of active research.

The clinical presentation of LCC is variable, with onset ranging from early infancy to late adulthood, although most cases are diagnosed in childhood or young adulthood. While a slight female predominance has been observed, both sexes are affected. Symptoms arise from the combined effects of leukoencephalopathy, calcifications, and cysts, and can include headaches, slowing of cognitive performance, seizures, visual disturbances, and a combination of extrapyramidal, cerebellar, and pyramidal features. These clinical manifestations are thought to result from the cerebral microangiopathy, which is characterized by angiomatous-like blood vessels associated with gliosis and the deposition of Rosenthal fibers, a prominent pathological hallmark of the disease.