Good Outcome of Resective Epilepsy Surgery in a 1-Year-Old Child with Drug-Resistant Focal Epilepsy with a Novel Pathogenic COL4A1 Mutation

Abstract

Pathogenic variants in COL4A1, encoding the α chain of type IV collagen, have been associated with cerebrovascular pathology as well as malformations of cortical development, thereby causing structural epilepsy. This case illustrates successful resective epilepsy surgery in a 12-month-old girl with left occipital focal cortical dysplasia (FCD) associated with a heterozygous splice-donor variant in COL4A1. She presented with drug-resistant focal epilepsy with daily seizures from the age of 2 months, refractory to several combinations of antiseizure medications, as well as mild right-sided hemiparesis and developmental delay. All presurgical diagnostic modalities, including ictal and interictal electroencephalography, magnetic resonance imaging, and ictal fluorodeoxyglucose positron emission tomography, showed congruent findings, pointing toward one single left occipital epileptogenic zone (EZ). We performed a left occipital lobectomy, using intraoperative electrocorticography to confirm the boundaries of the EZ. After surgery, the patient has remained seizure free, and both cognitive and motor developments have improved. Histopathology of the resected brain tissue showed FCD type Ia. Resective epilepsy surgery can have a very good outcome, also in patients with genetic mutations in COL4A1, constituting a less invasive option than the previously used more radical surgical procedures such as hemispherectomy.

Keywords

genetic epilepsies - focal cortical dysplasia - malformations of cortical development - collagen - FCD

Consent for Publication

Written informed consent for publication was obtained from the patient's guardians.

Authors' Contribution

N.F. contributed to writing—original draft, writing—review and editing, investigation, and visualization; M.W. to writing—review and editing, and investigation; I.B. to writing—review and editing, and supervision; M.K. to writing—review and editing, and resources; C.V. to writing—review and editing, supervision, and project administration.

Publication History

Received: 31 March 2023

Accepted: 28 December 2023

Accepted Manuscript online:
02 January 2024

Article published online:
30 January 2024

• References

• 1 Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol 2011; 3 (01) a004978
• 2 Vahedi K, Alamowitch S. Clinical spectrum of type IV collagen (COL4A1) mutations: a novel genetic multisystem disease. Curr Opin Neurol 2011; 24 (01) 63-68
• 3 Gould DB, Phalan FC, van Mil SE. et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 2006; 354 (14) 1489-1496
• 4 Gould DB, Phalan FC, Breedveld GJ. et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005; 308 (5725) 1167-1171
• 5 Yoneda Y, Haginoya K, Kato M. et al. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Ann Neurol 2013; 73 (01) 48-57
• 6 Zagaglia S, Selch C, Nisevic JR. et al. Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease. Neurology 2018; 91 (22) e2078-e2088
• 7 Meuwissen MEC, Halley DJJ, Smit LS. et al. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. Genet Med 2015; 17 (11) 843-853
• 8 Labelle-Dumais C, Dilworth DJ, Harrington EP. et al. COL4A1 mutations cause ocular dysgenesis, neuronal localization defects, and myopathy in mice and Walker-Warburg syndrome in humans. PLoS Genet 2011; 7 (05) e1002062
• 9 Najm I, Lal D, Alonso Vanegas M. et al. The ILAE consensus classification of focal cortical dysplasia: an update proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia 2022; 63 (08) 1899-1919
• 10 Hino-Fukuyo N, Kikuchi A, Iwasaki M. et al. Dramatic response after functional hemispherectomy in a patient with epileptic encephalopathy carrying a de novo COL4A1 mutation. Brain Dev 2017; 39 (04) 337-340
• 11 Papandreou A, Tisdall MM, Chong WK, Cross JH, Harkness WF, Varadkar SM. COL4A1 mutations should not be a contraindication for epilepsy surgery. Childs Nerv Syst 2014; 30 (08) 1467-1469
• 12 Tavtigian SV, Harrison SM, Boucher KM, Biesecker LG. Fitting a naturally scaled point system to the ACMG/AMP variant classification guidelines. Hum Mutat 2020; 41 (10) 1734-1737
• 13 Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med 2011; 365 (10) 919-926
• 14 Stevelink R, Sanders MW, Tuinman MP. et al. Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review. Epileptic Disord 2018; 20 (02) 99-115
• 15 Holthausen H, Coras R, Tang Y. et al. Multilobar unilateral hypoplasia with emphasis on the posterior quadrant and severe epilepsy in children with FCD ILAE type 1A. Epilepsia 2022; 63 (01) 42-60