Congenital Brain Malformation (Lissencephaly) with Drug-Resistant Structural Multifocal Epilepsy and Severe Motor Impairment: a Case Report

Lissencephaly is a severe cortical malformation associated with impaired neuronal migration. Clinically, it may manifest with early-onset epileptic seizures, marked psychomotor developmental delay, muscle tone abnormalities, and persistent motor deficit []. PAFAH1B1-associated forms are characterized by a broad phenotypic spectrum, including feeding difficulties, poor head control, spasticity, visual impairment, and a high frequency of drug-resistant epileptic seizures.
The presented case demonstrates a congenital brain malformation associated with severe motor impairment (GMFCS V/ MACS V), drug-resistant structural multifocal epilepsy, pseudobulbar syndrome, chronic aspiration syndrome, nutritional insufficiency, and neurogenic dysfunction of the pelvic organs.
The aim of this case report is to demonstrate the importance of comprehensive multidisciplinary assessment in a patient with lissencephaly, drug-resistant epilepsy, and multiple somatic complications, as well as the need for careful interpretation of genetic findings until familial validation of the identified variant is completed.

1. Pilz DT, Quarrell OW. Syndromes with lissencephaly. J Med Genet. 1996;33(4):319–323. doi: 10.1136/jmg.33.4.319

2. Brock S, Dobyns WB, Jansen A. PAFAH1B1-related lissencephaly / Subcortical Band Heterotopia. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. [2009 Mar 3]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2009. PMID: 20301752

3. Cardoso C, Leventer RJ, Dowling JJ, et al. Clinical and molecular basis of classical lissencephaly: mutations in the LIS1 gene (PAFAH1B1). Hum Mutat. 2002;19(1):4‒15. doi: 10.1002/humu.10028

4. Kolbjer S, Martin DA, Pettersson M, et al. Lissencephaly in an epilepsy cohort: molecular, radiological and clinical aspects. Eur J Paediatr Neurol. 2021;30:71‒81. doi: 10.1016/j.ejpn.2020.12.011

5. Faccioli S, Pagliano E, Ferrari A, et al. Evidence-based management and motor rehabilitation of cerebral palsy children and adolescents: a systematic review. Front Neurol. 2023;14:1171224. doi: 10.3389/fneur.2023.1171224

6. Calderone A, Militi D, Cardile D, et al. Swallowing disorders in cerebral palsy: a systematic review of oropharyngeal dysphagia, nutritional impact, and health risks. Ital J Pediatr. 2025;51:57. doi: 10.1186/s13052-025-01903-1

7. Erasmus CE, van Hulst K, Rotteveel JJ, et al. Clinical practice: swallowing problems in cerebral palsy. Eur J Pediatr. 2012;171(3):409‒414. doi: 10.1007/s00431-011-1570-y

8. Palisano R, Rosenbaum P, Walter S, et al. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol. 1997;39(4):214‒223. doi: 10.1111/j.1469-8749.1997.tb07414.x

9. Paulson A, Vargus-Adams J. Overview of four functional classification systems commonly used in cerebral palsy. Children (Basel). 2017;4(4):30. doi: 10.3390/children4040030