Cavitating leukoencephalopathy (CLE) is an imaging clinical syndrome characterized by cavities in the white matter and the acute onset of neurological dysfunction. It should be classified as the myelin vacuolization in the classification system of leukodystrophies based on pathological changes in 2017.

To get an overall understanding of CLE, we recruited 37 children who met the criteria of CLE from 2009 to 2018. Whole-exome sequencing and follow-up study with a median of 23.5 months were performed.

Genotypic spectrum: pathogenic or likely pathogenic mutations were identified in eight genes, including IBA57 (17/37), NDUFS1 (5/37), NDUFV1 (2/37), NDUFV2 (3/37), NDUFAF5 (1/37), LYRM7 (1/37), NDUFB8 (1/37) and GLRX5 (1/37). Natural course: the median age at disease onset was 11 months. All cases had acute or subacute onset, and the median time at which the deterioration of neurological function reached its nadir phase was 1 month. 35/37 (94.59%) showed motor regression. Then, the condition of most patients gradually stabilized or even improved (94.59%, 35/37), except two deaths. Some cases presented visual impairment (32.43%, 12/37), epilepsy (29.73%, 11/37) and nystagmus (18.92%, 7/37). Neuroimaging features: cavities and high-intensity diffusion-weighted imaging (DWI) signals were observed in the white matter in the peak phase and then gradually reduced. 84% (21/25) remained high-intensity DWI signals for a long time, and 38.10% (8/21) presented new high-intensity DWI signals.

CLE is a group of heterogeneous disorders due to different gene mutations. Most patients share similar natural course and neuroimaging features. IBA57 is the most common candidate gene.