Dominant negative or haploinsufficient mutations in the collagen genes COL4A1 and COL4A2 are characterized by arterial basement membrane thickening resulting in a multisystem microangiopathy targeting the CNS but also potentially affecting the ocular, renal, cardiac, and muscular systems. Within the brain, such changes predispose affected individuals to recurrent ischemic and/or hemorrhagic strokes beginning during early fetal development but extending into the postnatal period and even into adulthood.¹ Mutations affecting glycine residues of the Gly-Xaa-Yaw (typically representing glycine-proline-4-trans-hydroxyproline in vertebrates) repeat domains that typify collagens usually manifest in an autosomal dominant (AD) fashion. However, recent work suggests that tissue-specific mutation effects may also occur, with mutations leading to gain of function effects in some tissues and loss of function effects in others.² Stroke-related complications may be insidious and clinically silent. Neuroimaging phenotypes of COL4A-associated disease include chronic white matter disease, porencephaly/hydranencephaly, encephalomalacia, cerebral calcifications, schizencephaly and hydrocephalus and corresponding clinical diagnoses of cerebral palsy, intellectual disability, cortical visual impairment, and epilepsy.³

胶原基因COL4A1和COL4A2的显性负突变或单倍体不足突变的特征是动脉基底膜增厚，导致靶向CNS的多系统微血管病，但也可能影响眼，肾，心脏和肌肉系统。在大脑内部，这种变化使受影响的个体容易在胎儿发育早期开始反复发作缺血性和/或出血性中风，但一直持续到出生后甚至成年。^1个影响Gly-Xaa-Yaw的甘氨酸残基的突变（通常在脊椎动物中代表甘氨酸-脯氨酸-4-反式-羟基脯氨酸）重复域，通常以常染色体显性（AD）方式显示胶原蛋白。但是，最近的工作表明，也可能发生组织特异性突变效应，这种突变导致某些组织的功能效应获得，而另一些组织的功能丧失。²中风相关的并发症可能是隐匿的，临床上无言。与COL4A相关的疾病的神经影像学表现型包括慢性白质病，头颅/脑瘫，脑水肿，脑钙化，裂脑和脑积水，以及相应的脑瘫，智力障碍，皮质视力障碍和癫痫的临床诊断。³