Leukoencephalopathy with spot-like calcifications caused by recessive COL4A2 variants

Abstract

Dominant COL4A1 and COL4A2 mutations cause a broad spectrum of cerebrovascular diseases, whose onset varies from fetal to adult life, mostly represented by prenatal-neonatal intracerebral hemorrhage with porencephaly and by periventricular leukomalacia with calcifications, corresponding clinical diagnoses of cerebral palsy mimics. Axenfeld-Rieger syndrome with leukoencephalopathy, HANAC syndrome, young- and late-onset stroke and malformation of cortical development are rarer presentations. Very recently, the existence of recessive COL4A1- and COL4A2-related forms has been documented. We broaden the phenotypic and genotypic spectra of COL4A2-related disease by describing this second family with recessive pathogenic variants and neuroimaging phenotype of leukoencephalopathy with spot-like calcifications.

Keywords: COL4A1; Calcifications; Leukodystrophy; Recessive; Stroke.