Sporadic periventricular nodular heterotopia: Classification, phenotype and correlation with Filamin A mutations

•The course and outcome of epilepsy was significantly “worse” in unilateral heterotopia patients.•Most patients with “classical” heterotopia were females, likely to have arachnoid cysts and cardiac abnormalities, but were mostly seizure-free.•Hippocampal abnormalities, neurological deficits and cerebellar abnormalities were more common in patients with bilateral asymmetrical heterotopia.

ObjectiveThe purpose of this study was to better delineate the clinical spectrum of periventricular nodular heterotopia (PNH) in a large patient population after long term follow up. Specifically, this study aimed to relate PNH subtypes to clinical or epileptic outcomes, epileptic discharges and underlying Filamin A (FLNA) mutations by analyzing anatomical features.MethodsThe study included 100 patients with radiologically confirmed nodular heterotopia. Patients' FLNA gene sequences and medical records were analyzed. Two-sided Chi-square test and Fisher's exact t-test were used to assess associations between the distribution of PNHs and specific clinical features.ResultsBased on imaging data, patients were subdivided into three groups: (a) classical (bilateral frontal and body, n = 41 patients), (b) bilateral asymmetrical or posterior (n = 16) and (c) unilateral heterotopia (n = 43). Most patients with classical heterotopia were females (P = 0.033) and were likely to have arachnoid cysts (P = 0.025) and cardiac abnormalities (P = 0.041), but were mostly seizure-free. Additionally, hippocampal abnormalities (P = 0.022), neurological deficits (P = 0.028) and cerebellar abnormalities (P = 0.005) were more common in patients with bilateral asymmetrical heterotopia. Patients with unilateral heterotopia were prone to develop refractory epilepsy (P = 0.041). FLNA mutations were identified in 8 patients.ConclusionsEach group's distinctive genetic mutations, epileptic discharge patterns and overall clinical outcomes confirm that the proposed classification system is reliable. These findings could not only be an indicator of a more severe morphological and clinical phenotype, but could also have clinical implications with respect to the epilepsy management and optimization of therapeutic options.