8th Baltic Congress of Radiology

Neuroradiology

oral abstract

Children with antenatal hemorrhage and/or porencephaly have been shown to have high incidence of pathogenic changes in COL4A1/A2 genes. The etiology of presumed antenatal periventricular venous infarction (PVI), diagnosed with periventricular white matter damage and porencephaly after the neonatal period, is not clear. The aim of this study was to evaluate genetic risk factors in children with antenatal, presumed antenatal and neonatal PVI and to find radiological signs characteristic of genetic cause of the stroke.

Genetic analysis and magnetic resonance imaging (MRI) were performed in 85 children with PVI: term born children (≥36 gestational weeks) with antenatal (n=6) or presumed antenatal (n=40) PVI and preterm children (<36 gestational weeks) with neonatal PVI (n=39). Genetic testing was performed using exome (n=60) or large gene panel (n=6700 genes) (n=23) sequencing, or single gene testing (n=2) before next-generation sequencing became available.

Pathogenic variants previously associated with a cerebrovascular disease were found in 11/85 (12.9%) children with PVI. In addition, variants of unknown significance were detected in 12/85 (14.1%) children. Among the pathogenic variants, COL4A1, COL4A2 and COL5A1 variants were most frequently found (7/11;63%). Pathogenic variants associated with coagulopathy were found in 2/11 (18%) children and other variants that can be associated with stroke, in 2/11 (18%). Children with collagenopathies had significantly more often severe findings in MRI compared to children with PVI without genetic changes in studied genes: bilateral multifocal porencephaly (p=0.0029), bilateral severe white matter loss (p=0.01), bilateral hyperintensities in the white matter (p=0.008), moderate to severe hydrocephalus (p=0.01), extensive bilateral periventricular gliosis (p=0.016), lacunes in the contralesional hemisphere (in the putamen) (p=0.0098), moderate to severe volume loss in the ipsilesional nucleus caudatus (p=0.018), putamen (p=0.0015) and thalamus (p=0.017). In 3/7 children with collagenopathies had computed tomography available and all of them had small bilateral parenchymal punctate calcifications. Neurodevelopmental outcome in children with pathogenic/likely pathogenic variants of collagen genes was poor. Severe hemiparesis/spastic quadriplegia and epilepsy developed more often in children with pathogenic variants in collagen genes compared to children without genetic variants (85.7% versus 20.7%) respectively, p=0.0013; OR=233 (95% CI: 2.8 – 531) and (57.1% versus 15.5% respectively, p= 0.025; OR=7.3 (95% CI: 1.3 – 41), respectively.

Our data suggest that children with PVI have high prevalence of pathogenic variants in collagene genes (COL4A1/A2 and COL5A1) and these variants are more often associated with bilateral severe brain damage and poor neurodevelopmental outcome. All children with PVI, especially those with bilateral multifocal strokes, need genetic testing. Collagenopathies (COL4A1/A2 and COL5A1/A2 genes) should be investigated first. This study was supported by the Estonian Research Council grants (PUT148, PRG471, MOBTP175, PSG774) and basic financing from the University of Tartu

Genetic analysis and magnetic resonance imaging were performed in 85 children with with periventricular venous infarction (PVI). Pathogenic variants associated with stroke were found in 12.9% children, including most frequently COL4A1/A2 and COL5A1 variants (63%). Children with collagenopathies had significantly more often severe findings in MRI and poor neurodevelopmental outcome, suggesting that genetic testing should be offered to children with PVI.

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