Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Clin Neurol Neurosurg. 2023 Feb;225:107584. doi: 10.1016/j.clineuro.2022.107584. Epub 2022 Dec 31.
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.
主要 COL4A1 和 COL4A2 突变导致广泛的脑血管疾病，其发病从胎儿期到成年期不等，主要表现为伴有脑裂畸形的产前-新生儿颅内出血和伴有钙化的脑室周围脑白质软化，相应的临床诊断为脑瘫样表现。Axenfeld-Rieger 综合征伴白质脑病、HANAC 综合征、早发和迟发性中风以及皮质发育畸形较为少见。最近，已经证实存在 COL4A1 和 COL4A2 相关的隐性形式。我们通过描述第二个具有隐性致病性变异和点状钙化的脑白质病神经影像学表型的家族，扩展了 COL4A2 相关疾病的表型和基因型谱。
