Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disease caused by mutations in the colony stimulating factor 1 receptor (CSF1R) gene that often results in cognitive impairment, psychiatric disorders, motor dysfunction and seizure. We report familial cases of a novel CSF1R mutation causing HDLS similar to hydrocephalus. The patients initially presented with a gait disturbance and then developed progressive cognitive decline, urinary incontinence, epileptic seizures and became bedridden as the disease progressed. A brain magnetic resonance imaging (MRI) scan revealed striking ventricular enlargement and diffuse brain atrophy with frontotemporal predominance, which was later accompanied by white matter changes. Genetic testing in this family showed a novel c.2552T>C (p.L851P) mutation in exon 19 of the CSF1R gene. However, three gene carriers in the family remained clinically asymptomatic. Because of its heterogeneous clinical phenotypes, HDLS patients are often misdiagnosed with other diseases. This is the first genetically proven HDLS case resembling hydrocephalus, and the clinical symptoms of HDLS may be related to the specific genetic mutation.

中文翻译：

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遗传性弥漫性白质脑病家族中的一种新型CSF-1R突变，其中轴突类球体被误诊为脑积水。

带有轴突球体的遗传性弥漫性白质脑病（HDLS）是一种罕见的常染色体显性疾病，由集落刺激因子1受体（CSF1R）基因突变引起，通常导致认知障碍，精神病，运动功能障碍和癫痫发作。我们报告家族病例的新型CSF1R突变导致类似于脑积水的HDLS。患者最初表现为步态障碍，然后逐渐发展为认知能力下降，尿失禁，癫痫发作，并随着疾病的进展而卧床不起。脑磁共振成像（MRI）扫描显示，前额颞叶占优势，脑室明显增大，弥漫性脑萎缩，随后伴有白质改变。该家族的基因测试显示出一种新颖的c.2552T> C（p。CSF1R基因第19外显子的L851P）突变。但是，该家族中的三种基因携带者在临床上仍无症状。由于HDLS患者的临床表型各异，因此常被误诊为其他疾病。这是首例经遗传学证实的脑积水类似HDLS的病例，HDLS的临床症状可能与特定的基因突变有关。