Leukoencephalopathy with calcifications and cysts (LCC)
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.
Clinical manifestations
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. Unlike Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), LCC does not present with systemic manifestations.
References
- Paff, Michelle, et al. "Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease." BMC neurology 22 (2022): 1-6.
Calcifications and cysts in the deep nuclei
Calcifications and cysts are observed in the basal ganglia, specifically in the putamen, globus pallidus, caudate nucleus, and thalamus. These lesions are usually bilateral but may exhibit asymmetry.
White matter abnormal signal and calcifications
On T2-weighted and FLAIR imaging, diffuse hyperintensity is observed in the periventricular white matter, with the subcortical U-fibers and corpus callosum are relatively spared. The calcifications are typically located in the cortex and white matter of the brain, with a predilection for the frontal and parietal lobes. However, they can occur anywhere within the cerebrum.