Abstract：
We report three siblings homozygous for CSF1R variant c.1969 + 115_1969 + 116del to expand the phenotype of \"brain abnormalities, neurodegeneration, and dysosteosclerosis\" (BANDDOS) and discuss its link with \"adult leukoencephalopathy with axonal spheroids and pigmented glia\" (ALSP), caused by heterozygous CSF1R variants. We evaluated medical, radiological, and laboratory findings and reviewed the literature. Patients presented with developmental delay, therapy-resistant epilepsy, dysmorphic features, and skeletal abnormalities. Secondary neurological decline occurred from 23 years in sibling one and from 20 years in sibling two. Brain imaging revealed multifocal white matter abnormalities and calcifications during initial disease in siblings two and three. Developmental brain anomalies, seen in all three, were most severe in sibling two. During neurological decline in siblings one and two, the leukoencephalopathy was progressive and had the MRI appearance of ALSP. Skeletal survey revealed osteosclerosis, most severe in sibling three. Blood markers, monocytes, dendritic cell subsets, and T-cell proliferation capacity were normal. Literature review revealed variable initial disease and secondary neurological decline. BANDDOS presents with variable dysmorphic features, skeletal dysplasia, developmental delay, and epilepsy with on neuro-imaging developmental brain anomalies, multifocal white matter abnormalities, and calcifications. Secondary neurological decline occurs with a progressive leukoencephalopathy, in line with early onset ALSP. Despite the role of CSF1R signaling in myeloid development, immune deficiency is absent. Phenotype varies within families; skeletal and neurological manifestations may be disparate.
摘要：
我们报告了CSF1R变体c.1969+115_1969+116del纯合的三个兄弟姐妹，以扩大“脑异常”的表型，神经变性,和肌营养不良症（BANDDOS），并讨论其与“具有轴突球体和色素胶质细胞的成人白质脑病”（ALSP）的联系，由杂合CSF1R变体引起。我们评估了医学，放射学,和实验室研究结果，并回顾了文献。出现发育迟缓的患者，难治性癫痫，变形特征，和骨骼异常。继发性神经系统衰退发生在兄弟姐妹1的23年和兄弟姐妹2的20年。脑成像显示兄弟姐妹2和3的初始疾病期间多灶性白质异常和钙化。大脑发育异常,在这三个人中都看到了，兄弟姐妹中最严重。在兄弟姐妹1和2的神经系统衰退期间，白质脑病为进行性,MRI表现为ALSP.骨骼调查显示骨硬化，兄弟姐妹三最严重。血液标记物,单核细胞,树突状细胞亚群，T细胞增殖能力正常。文献综述显示可变的初始疾病和继发性神经系统衰退。BANDDOS具有可变的变形特征，骨骼发育不良,发育迟缓,与神经成像发育大脑异常的癫痫，多灶性白质异常，和钙化。继发性神经衰退发生在进行性白质脑病，符合早发性ALSP。尽管CSF1R信号在骨髓发育中的作用，不存在免疫缺陷。表型在家庭内不同；骨骼和神经系统表现可能不同。
