Laminin α2 gene (LAMA2)-related Congenital Muscular Dystrophy (CMD) was distinguished by a defining central nervous system (CNS) abnormality—aberrant white matter signals by MRI—when first described in the 1990s. In the past 25 years, researchers and clinicians have expanded our knowledge of brain involvement in LAMA2-related CMD, also known as Congenital Muscular Dystrophy Type 1A (MDC1A). Neurological changes in MDC1A can be structural, including lissencephaly and agyria, as well as functional, including epilepsy and intellectual disability. Mouse models of MDC1A include both spontaneous and targeted LAMA2 mutations and range from a partial loss of LAMA2 function (e.g., dy^2J/dy^2J), to a complete loss of LAMA2 expression (dy^3K/dy^3K). Diverse cellular and molecular changes have been reported in the brains of MDC1A mouse models, including blood-brain barrier dysfunction, altered neuro- and gliogenesis, changes in synaptic plasticity, and decreased myelination, providing mechanistic insight into potential neurological dysfunction in MDC1A. In this review article, we discuss selected studies that illustrate the potential scope and complexity of disturbances in brain development in MDC1A, and as well as highlight mechanistic insights that are emerging from mouse models.

层粘连蛋白α2基因（LAMA2）相关的先天性肌营养不良症（CMD）的特征在于定义的中枢神经系统（CNS）异常-MRI产生的异常白质信号-在1990年代首次被描述时。在过去的25年中，研究人员和临床医生扩大了我们对LAMA2相关CMD（也称为先天性肌营养不良1A型（MDC1A））的大脑参与程度的了解。MDC1A的神经系统变化可能是结构性的，包括lissencephaly和agyria，也可能是功能性的，包括癫痫和智力障碍。MDC1A的小鼠模型既包括自发性LAMA2突变，也包括针对性LAMA2突变，其范围包括部分LAMA2功能丧失（例如，dy ^2J / dy ^2J），导致LAMA2表达完全丧失（dy^3K /dy^3K）。据报道，MDC1A小鼠模型的大脑中存在多种细胞和分子变化，包括血脑屏障功能障碍，神经和胶质细胞生成改变，突触可塑性变化和髓鞘减少，从而提供了对MDC1A潜在神经功能障碍的机械观察。在这篇综述文章中，我们讨论了一些选定的研究，这些研究阐明了MDC1A大脑发育障碍的潜在范围和复杂性，并重点介绍了从小鼠模型中获得的机制性见解。