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Correspondence to Dr Linford Fernandes, Department of Neurology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3EX, UK; [email protected]
A Caucasian woman in her 50s had a 6-month history of progressive left arm and leg weakness with difficulty walking and inco-ordination. She also had intermittent visual blurring and poor memory. She had been previously well with no relevant family history. On examination, there was a left hemiparesis and ataxic gait.
CT and MR scans of the brain showed extensive leukoencephalopathy with cysts and multiple foci of calcification (figure 1). Cerebrospinal fluid analysis showed oligoclonal bands but was otherwise normal. Plasma amino acids, white cell enzymes, very-long-chain fatty acids and bile acids were normal.
Given the striking brain imaging features, our neuroradiologist suggested a diagnosis of leukoencephalopathy with calcifications and cysts. We screened the patient for genetic variants in the SNORD118 gene using Sanger sequence analysis, as the clinical genetics team advised that this test had a quicker turnaround time than a white matter panel or whole genome sequencing. The Sanger sequence analysis showed the patient was heterozygous for two pathogenic SNORD118 variants, NR_033294.1 n.*5C>G and n.*9C>T.
SNORD118 is a non-protein-coding gene producing a small nucleolar RNA, the box C/D snoRNA U8, involved in ribosome biogenesis and function.1 Leukoencephalopathy with calcifications and cysts (also known as Labrune’s syndrome) was first described in 1996 in three unrelated children. Patients present with progressive cognitive impairment, seizures, ataxia as well as pyramidal and extrapyramidal symptoms.2 It is characterised histologically by fibrinoid deposition in the mural tissues of the cerebral microvasculature, and Rosenthal fibre formation, which are clumped intermediate filament proteins that primarily contain glial fibrillar acidic protein. Occasionally, there is abnormal proliferation of the cerebral microvasculature, leading to microhaemorrhages.3 The condition commonly presents in childhood but there are adult onset cases described with a...