Ataxia, Intellectual Disability, and Ocular Apraxia with Cerebellar Cysts: A New Disease?

Cerebellar cysts are rare findings in pediatric neuroimaging and rather characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim to report on seven children with cerebellar cysts showing absence of weakness and ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about neurological and ophthalmological features, outcome, and creatine kinase values were collected from clinical histories and follow-up examinations. All MR images were qualitatively evaluated for infra-and supratentorial abnormalities. A SNP 6.0-Array was performed in three children. The POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56 genes were screened in all patients by Sanger sequencing. Seven children from five families were studied. Ataxia, intellectual disability, and language impairment were found in all patients, ocular motor apraxia in five, and severe myopia in three. None of the patients had weakness, only three a minimally increased creatine kinase value. Qualitative neuroimaging evaluation showed cerebellar cysts and dysplasia in the cerebellar hemispheres and vermis in all children. Additional findings were an enlarged fourth ventricle in all children, vermian hypoplasia and brain stem morphological abnormalities in five. The SNP array showed no pathogenetic imbalances in all children evaluated. In all patients, no mutations were found in POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56. The peculiar combination of the same clinical and neuroimaging findings in our patients highly suggests that this phenotype may represent a novel entity, possibly falling within the spectrum of dystroglycanopathies.