GATOR1相关癫痫的神经影像谱系（GATORopathies）

BACKGROUND: The mTOR pathway is important for neurodevelopment. The GATOR1 complex, composed of DEPDC5, NPRL2, and NPRL3, functions as a negative regulator of mTORC1 activity and pathogenic variants in the genes which comprise this complex cause focal epilepsy and malformation of cortical development, all named as GATORopathies. While focal cortical dysplasia is commonly reported, the full spectrum of associated neuroimaging findings remains incompletely defined.

OBJECTIVE: To characterize the neuroimaging features associated with GATOR1 complex mutations and to explore potential associations between imaging phenotypes and specific genotypes.

METHODS: MRI studies were retrospectively reviewed from January 2019 to December 2025 in patients with genetically confirmed GATOR1 mutations. Clinical, radiological, and genetic data were analyzed to identify imaging patterns and genotype-phenotype correlations.

RESULTS: Twenty patients (median age : 6 years; range 1-25 years) were included. DEPDC5 mutations were most frequent (n = 12), followed by NPRL3 (n = 5) and NPRL2 (n = 3). MRI abnormalities were identified in 16 patients (80%). Focal cortical malformations were the most common finding (n = 8), followed by diffuse cortical malformations (n = 5) and generalized neuroparenchymal atrophy (n = 3); four patients had MRI-negative studies. Imaging findings varied considerably across genotypes. DEPDC5 and NPRL2 mutations showed a broad and heterogeneous radiological spectrum, whereas NPRL3 mutations showed a tendency toward cortical malformations, though the small subgroup size limits interpretation. Seizure onset spanned from infancy to adulthood; however, patients with diffuse cortical abnormalities or generalized neuroparenchymal atrophy tended to present earlier and experienced a greater seizure burden.

CONCLUSION: GATOR1-related epilepsy demonstrates substantial variability in neuroimaging and electroclinical features, extending beyond focal cortical malformations to include diffuse cortical malformations, generalized neuroparenchymal atrophy, and MRI-negative presentations. These findings highlight the value of integrated genetic, imaging, and electroclinical assessment in routine clinical practice.