Case Report: Leukoencephalopathy with calcifications and cysts caused by novel biallelic SNORD118 variants in a childhood-onset patient with long-term follow-up

Background Labrune syndrome, also termed leukoencephalopathy with calcifications and cysts (LCC), is a rare autosomal recessive cerebral microangiopathy associated with pathogenic variants of the SNORD118 gene. Long-term clinical follow-up of childhood-onset LCC progressing into adulthood is limited in the literature. Case presentation We present a 24-year-old woman whose neurological symptoms began at age 6 years with recurrent headaches and visual disturbances. Learning difficulties emerged at age 7 years. At age 22 years, she developed probable focal-onset seizures with bilateral tonic–clonic evolution, preceded by headache and blurred vision. At age 24 years, cognitive assessment showed a Mini-Mental State Examination score of 12, indicating significant impairment. Neuroimaging demonstrated the characteristic triad of diffuse white matter abnormalities, intracranial calcifications, and parenchymal cysts with fluid levels. Histopathological examination of a left frontal lobe biopsy demonstrated telangiectatic vessels, fibrinoid necrosis, hemosiderin deposition, and reactive gliosis, consistent with chronic cerebral microangiopathy. Whole-genome sequencing identified compound heterozygous SNORD118 variants, including the previously reported n.24C>T variant and the novel n.103G>C variant. Parental segregation confirmed that the two variants were inherited from different parents and were located in trans. The patient was treated with lacosamide 100 mg twice daily, with partial reduction in seizure frequency. Bevacizumab was discussed but declined for financial reasons. Conclusion This case illustrates the long-term clinical course of childhood-onset LCC extending into adulthood and highlights the value of integrating characteristic neuroimaging, histopathology, and genetic testing. The patient’s longitudinal clinical history, together with pathological evidence of chro nic cerebral microangiopathy, is consistent with the progressive vascular phenotype previously described in LCC, although prospective radiological progression was not documented during the most recent follow-up. The novel SNORD118 n.103G>C variant was classified as Likely Pathogenic according to the applied ACMG/AMP framework; however, its pathogenic effect has not been experimentally validated.