新描述的末端截断变异的临床放射学谱扩展
Extension of the Clinicoradiologic Spectrum of Newly Described End-Truncating Variations.
作者信息
Morel Hélène, Bailly Laurent, Urbanczyk Cédric, Hervé Dominique, Berroir Stéphane, Le Bouc Raphaël, Levy Richard, Meyer Mylène, Aloui Chaker, Tournier-Lasserve Elisabeth, Mathey Guillaume
机构信息
Université de Paris (H.M., D.H., C.A., E.T.-L.), INSERM UMR 1141 NeuroDiderot; AP-HP (H.M., E.T.-L.), Service de Génétique Moléculaire Neurovasculaire, Hôpital Saint-Louis; Reference Centre for Rare or Early-Onset Dementias (L.B., R.L.B., R.L.), IM2A, Département de Neurologie, AP-HP - Hôpital Pitié-Salpêtrière, Paris; Centre Hospitalier Départemental La Roche-Sur-Yon (C.U.), Service de Neurologie, La Roche-Sur-Yon; AP-HP (D.H.), CERVCO, Centre de Neurologie Vasculaire Translationnelle, Hôpital Lariboisière; Service de Neurologie (S.B.), Centre Hospitalier Alpes Leman, Contamine sur Arve; and Service de Neurologie (M.M., G.M.), Centre Hospitalier Regional Universitaire de Nancy, France.
出版信息
Neurol Genet. 2023 Apr 12;9(3):e200069. doi: 10.1212/NXG.0000000000200069. eCollection 2023 Jun.
OBJECTIVES
To refine the clinical spectrum of a very recently identified phenotype associated with end-truncating pathogenic variations.
METHODS
Detailed clinical, neuropsychological, and MRI investigation of 6 patients from 2 unrelated families segregating end-truncating variations.
RESULTS
All patients harbored end-truncating pathogenic variation. The specific association of a hippocampal type episodic memory dysfunction and a diffuse leukoencephalopathy was observed in all 4 patients aged older than 50 years, slightly worsening over time in 2 patients with several years of follow-up. Additional unspecific neurologic symptoms are reported, such as episodes of numbness, language troubles, or faintness in these 4 patients and the 2 younger ones.
DISCUSSION
The association of an extensive leukoencephalopathy with an episodic memory dysfunction of the hippocampal type is strongly suggestive of a end-truncating variation in adults older than 50 years. Early cognitive complaints and imaging abnormalities might exist decades before. Additional transient manifestations can be observed, and this association should lead to screening to avoid unnecessary invasive investigations.
目的
细化一种最近发现的与截短型致病变异相关的表型的临床谱。
方法
对来自2个不相关家族的6例携带截短型变异的患者进行详细的临床、神经心理学和MRI检查。
结果
所有患者均携带截短型致病变异。在所有4例年龄超过50岁的患者中均观察到海马型情景记忆功能障碍与弥漫性白质脑病的特定关联，在2例经过数年随访的患者中，这种关联随时间略有加重。在这4例年龄较大的患者以及2例较年轻的患者中还报告了其他非特异性神经症状，如麻木发作、语言障碍或头晕。
讨论
广泛的白质脑病与海马型情景记忆功能障碍的关联强烈提示50岁以上成年人存在截短型变异。早期认知主诉和影像学异常可能在数十年前就已存在。还可观察到其他短暂表现，这种关联应促使进行筛查以避免不必要的侵入性检查。
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