Padaczka i zaburzenia rozwojowe mózgu spowodowane inwersją-duplikacją chromosomu 15: Opis charakterystyki padaczki i wyników leczenia

OBJECTIVE: Inversion-duplication syndrome of chromosome 15 (invdup15) is a chromosomal disorder characterized by an inverted duplication of 15q11.2-q13.1. Epilepsy is highly prevalent (60%-80%), drug-resistant, and may progress to developmental epileptic encephalopathies (DEEs) such as Lennox-Gastaut syndrome (LGS). Despite its impact, epilepsy and optimal treatments remain poorly described. METHODS: A retrospective multicenter study across 37 Spanish hospitals analyzed 54 patients, divided into two genetic subgroups: invdup15q and intdup15q. Clinical and genetic data were reviewed, focusing on epilepsy onset, seizure types, syndrome progression, electroencephalographic (EEG) findings, and treatment response. RESULTS: Epilepsy was present in 29 of 54 (54%) patients, with a mean age at onset of 7.4 years (range = 1 month-24 years, SD = 6.4). LGS (16/29, 55%) and focal epilepsy (15/29, 52%) were the most frequent epilepsy types, although infantile epileptic spasms predominated in younger patients (5/6, 83%). Late onset LGS (>8 years) occurred in 38%. Initial seizures were mostly focal motor (10/29, 34%) and generalized tonic-clonic seizures (8/29, 28%), later evolving to tonic, myoclonic, and atypical absence seizures. Twenty-six of 29 (90%) reported drug-resistant epilepsy. Epilepsy was more frequent (65% vs. 35%, p < .05) and had earlier onset (median = 5.7 vs. 12.3 years) in invdup15q than intdup15q. EEG demonstrated unusual activities including diffuse fast activity, along with repetitive trains of paroxysmal fast activity during sleep. The most effective antiseizure drugs were oxcarbazepine for focal (9/11, 81%) and for generalized (2/3, 67%) epilepsy and valproic acid (6/10, 60%) for generalized epilepsy, whereas vigabatrin, zonisamide, and brivaracetam showed limited efficacy. In LGS, oxcarbazepine (8/12, 66%), valproic acid (11/18, 61%), and cannabidiol (6/9, 66%) yielded the best responses. All patients had early developmental delay; autism spectrum disorder was diagnosed in 22 of 54 (41%) and behavioral disorders in 30 of 54 (56%). SIGNIFICANCE: Epilepsy in invdup15 is highly drug-resistant and exhibits features consistent with DEEs, particularly LGS. EEG findings may serve as disorder biomarkers. Oxcarbazepine and valproic acid were the treatments most often associated with seizure improvement in this sample.