Di Donato I, Banchi S, Federico A, Dotti M T
Department of Medicine, Surgery and Neuroscience, University of Siena, via Banchi di Sotto, 55, 53100 Siena, Italy.
Curr Mol Med. 2014;14(8):944-958. doi: 10.2174/1566524014666141010130545.
Inherited white matter (WM) disorders include a heterogenous group of disorders affecting brain white matter and associated with myelin, axonal and glial cells or vascular pathology. Often a wide range of overlapping neurological manifestations possibly associated with variable systemic involvement are found in these disorders making clinical diagnosis challenging. Advances in molecular genetics enabled the identification of the responsible genes of an increasing number of previously undefined forms. This review focuses on genetic leukoencephalopathies with exclusive adulthood presentation, most of which have an autosomal dominant inheritance. The most common forms are related to vascular pathology, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), COL4A1-related leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy (RVCL), and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Also cerebroretinal microangiopathy with cysts and calcifications (CRMCC), which presents a prevalent infantile onset, will be detailed because of the vascular based myelin damage and the recent genetic characterization. Other adult onset (AO) leukoencephalopathies, such as the recently genetically defined hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), adult-onset autosomal dominant leukodystrophy (ADLD) due to LMNB1 duplication, adult polyglucosan body disease (APBD), and fragile X-associated tremor/ataxia syndrome (FXTAS) will be detailed shortly. Short notes on the clinical and MRI features of late onset variants of the classical infantile-onset leukodystrophies mostly related to metabolic disorders will also be given. Finally, palliative, curative and experimental treatment options are here summarized.
遗传性白质（WM）疾病包括一组异质性疾病，这些疾病影响脑白质，并与髓鞘、轴突、胶质细胞或血管病变相关。在这些疾病中，通常会发现一系列广泛的重叠神经学表现，可能伴有不同程度的全身受累，这使得临床诊断具有挑战性。分子遗传学的进展使得越来越多以前未明确的疾病形式的致病基因得以鉴定。本综述重点关注仅在成年期出现症状的遗传性脑白质病，其中大多数为常染色体显性遗传。最常见的形式与血管病变有关，如伴有皮质下梗死和白质脑病的脑常染色体显性动脉病（CADASIL）、伴有皮质下梗死和白质脑病的脑常染色体隐性动脉病（CARASIL）、COL4A1相关的白质脑病、伴有脑白质营养不良的视网膜血管病（RVCL）以及伴有硬化性白质脑病的多囊性脂膜骨发育异常（PLOSL）。由于基于血管的髓鞘损伤和最近的基因特征，还将详细介绍伴有囊肿和钙化的脑视网膜微血管病（CRMCC），其发病多在婴儿期。其他成年期起病（AO）的白质脑病，如最近在基因上明确的伴有轴突球体的遗传性弥漫性白质脑病（HDLS）、由于LMNB1重复导致的成年期起病的常染色体显性白质营养不良（ADLD）、成年型多葡聚糖体病（APBD）以及脆性X相关震颤/共济失调综合征（FXTAS），也将在短期内详细介绍。还将简要介绍经典婴儿期起病的白质营养不良的晚期起病变异型的临床和MRI特征，这些变异型大多与代谢紊乱有关。最后，总结了姑息、治愈和实验性治疗方案。
