Molecular Characterization of Cerebellar Dysplastic Gangliocytoma With Clinical and Radiological Correlations

The purpose of this report is to describe the clinical, molecular, and imaging findings of the dysplastic gangliocytoma of the cerebellum (also called Lhermitte–Duclos disease), a rare pathological entity, with an emphasis on the genotype–phenotype correlation to further clarify its etiology and long‐term effects. The case reported herein refers to an 11‐year‐old boy with pharmaco‐resistant epilepsy, which eventually was associated with headaches, vomiting, and papilledema as the disease progressed. His magnetic resonance imaging (MRI) scans were compatible with a left cerebellar dysplasia. He underwent surgical treatment (excision of dysplastic cerebellar tissue) and improved significantly, remaining seizure‐free over a 3‐year follow‐up. Histopathological analysis revealed an increase in myelinization of axons in the molecular layer, the absence of Purkinje cells, hypertrophy in the granular cell layer, and atrophy of the white matter of the cerebellum. Furthermore, we performed whole‐exome sequencing (WES) of the patient’s samples to look for abnormal genetic variants. However, even though overactivation of the mechanistic target of rapamycin pathway has been found to play an essential role in the pathogenesis of cerebellar dysplasia, we were unable to identify pathogenic germline variants that could be associated with the observed phenotype. In conclusion, cerebellar dysplasia of the cerebellum is a complex disease with progressive clinical features, including refractory seizures, that responds well to surgical treatment. Further molecular studies are warranted to elucidate the pathogenesis of this rare pathology.