Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain.
Department of Neurology, Hospital Severo Ochoa, Madrid, Spain.
Alzheimers Dement. 2014 Oct;10(5 Suppl):S284-9. doi: 10.1016/j.jalz.2013.09.013. Epub 2014 Jan 15.
In recent years, a benign variant of frontotemporal lobar degeneration (FTLD) has been recognized, with a particularly slow progression of cognitive deficits and scarce frontotemporal atrophy or hypoperfusion in neuroimaging studies. Patients with FTLD have been considered "phenocopies," with an underlying nondegenerative neurologic process.
We report the first family with three affected members having benign FTLD associated with C9ORF72 gene hexanucleotide expansion. Onset of symptoms occurred during the fifth decade, with naming and memory problems as the main features. Two siblings have stabilized at mild cognitive impairment or incipient dementia for more than a decade, and remain quite independent for their activities of daily living at the current ages of 69 and 65 years, respectively. Their mother's cognitive deterioration evolved slowly during >30 years.
This family demonstrates that a benign evolution can be part of the growing spectrum of clinical phenotypes associated with neurodegenerative diseases caused by the C9ORF72 hexanucleotide expansion. Screening of this genetic marker should be considered in cases with this slow deterioration, especially if there is a family history.
近年来，一种良性额颞叶变性（FTLD）变异型得到了认可，其认知功能缺损的进展特别缓慢，神经影像学研究中额颞叶萎缩或灌注不足也很少见。FTLD 患者被认为是“表型模拟”，存在潜在的非退行性神经过程。
我们报告了首例与 C9ORF72 基因六核苷酸扩展相关的良性 FTLD 家族，该家族有 3 名受影响的成员。症状发作于 50 多岁，主要特征为命名和记忆问题。2 名兄弟姐妹已稳定处于轻度认知障碍或早期痴呆 10 多年，分别在 69 岁和 65 岁时仍能独立生活自理。他们的母亲的认知功能恶化在 >30 年的时间里缓慢进展。
该家族表明良性进展可能是与 C9ORF72 六核苷酸扩展引起的神经退行性疾病相关的不断增长的临床表型谱的一部分。对于这种缓慢恶化的病例，特别是如果有家族史，应考虑进行这种遗传标记的筛查。
