Leukoencephalopathy with brain calcifications and cysts (SNORD118) [1 gene]

Biallelic variants in the SNORD118 gene, which encodes the U8 C/D box small nucleolar RNA, cause a rare brain disorder characterized by a neuroradiological triad: intracranial calcifications, parenchymal cysts, and leukodystrophy. This disorder is known as leukoencephalopathy with brain calcifications and cysts (LCC) (OMIM#614561), or Labrune syndrome. This disorder can debut at any age, from shortly after birth to late adulthood. Clinical presentation is widely variable. Symptoms range from progressive cerebellar or pyramidal signs to impaired cognitive function, epilepsy, and even acute neurological symptoms with non-specific clinical presentation, similarly to other leukoencephalopathies.

Unknown.
To date, only a hundred cases have been reported in the literature, but it could be underdiagnosed due to the fact that the gene-phenotype association has only recently been discovered. It is worth mentioning that this gene is not captured by commonly used exome sequencing kits and therefore requires a specific study.

This study allows identifying the molecular cause in patients with the leukoencephalopathy with brain calcifications and cysts disorder. Since the SNORD118 gene cannot be captured by commonly used exome sequencing kits, this study can allow identifying leukoencephalopathy patients who have already been studied and for whom no diagnosis has been reached.

The leukoencephalopathy with brain calcifications and cysts disorder is characterized by a combination of white matter hyperintensities, calcifications, and cysts on brain magnetic resonance imaging, with variable neurological signs.