Service d'Exploration de la Vision et Neuro-Ophtalmologie, Hôpital Roger-Salengro, CHRU de Lille, Lille Cedex, France.
Ophthalmology. 2011 Mar;118(3):564-73. doi: 10.1016/j.ophtha.2010.07.024. Epub 2010 Oct 29.
Kjellin's syndrome is a hereditary neuro-ophthalmologic syndrome. We describe the clinical phenotypes of 7 patients, identifying the responsible mutations for 4 of them. A 10-year ophthalmologic and neurologic follow-up of 5 patients allowed us to describe the disease's characteristics, early symptoms and progression, associated ocular signs, and retinal changes in carriers.
Retrospective clinical study and molecular genetics investigation.
The records of 7 patients with Kjellin's syndrome were analyzed retrospectively.
All patients underwent full neurologic and ophthalmologic examinations. The neurologic examinations included assessments of initial symptoms, intelligence quotient tests, psychologic tests, and either magnetic resonance imaging or computed tomography. The ophthalmologic examinations included visual acuity on an Early Treatment Diabetic Retinopathy Study chart, intraocular pressure color vision assessment, slit-lamp and fundus examination, Goldmann perimetry, fundus autofluorescence, optical coherence tomography and fluorescein angiography, electro-oculography, electroretinography, and flash visual evoked potentials. Direct sequencing of the SPG11 and SPG15 genes and gene-dosage analysis for the former were performed for 4 of these index patients.
Identification of new mutations in the SPG11 gene, validating its implication in Kjellin's syndrome.
The first signs appear before the age of 10 years, with late verbal development and difficulty running and walking. Life expectancy is between 30 and 40 years. The secondary ophthalmologic symptoms only moderately affect visual acuity. In addition to the classic symptoms, 3 of the 7 patients displayed small whitish lens opacities, and 3 neurologically unaffected parents (father or mother), all heterozygous carriers, exhibited whitish retinal dots. All the patients who were tested carried SPG11, not SPG15, mutations.
Neurologic signs of SPG11 mutations emerge in early infancy, with walking and language difficulties. Onset of paraplegia occurs at the end of the first decade or during the second decade. Retinal changes, an integral part of SPG11 mutations in this series of patients, are only observed once the paraplegia has become apparent.
Kjellin 综合征是一种遗传性神经眼科综合征。我们描述了 7 名患者的临床表型，确定了其中 4 名患者的致病突变。对 5 名患者进行了长达 10 年的眼科和神经随访，使我们能够描述疾病的特征、早期症状和进展、相关眼部体征以及携带者的视网膜变化。
回顾性临床研究和分子遗传学研究。
回顾性分析了 7 例 Kjellin 综合征患者的病历。
所有患者均接受了全面的神经眼科检查。神经检查包括初始症状评估、智商测试、心理测试、磁共振成像或计算机断层扫描。眼科检查包括 ETDRS 视力表视力、眼压、色觉评估、裂隙灯和眼底检查、Goldmann 视野计、眼底自发荧光、光学相干断层扫描和荧光素血管造影、眼电图、视网膜电图和闪光视觉诱发电位。对这 4 名索引患者进行了 SPG11 和 SPG15 基因的直接测序和前者的基因剂量分析。
鉴定 SPG11 基因中的新突变，验证其在 Kjellin 综合征中的作用。
首发症状出现在 10 岁之前，表现为语言发育迟缓、跑步和行走困难。预期寿命在 30 至 40 岁之间。继发性眼科症状仅中度影响视力。除了经典症状外，7 名患者中的 3 名还表现出小白点状晶状体混浊，3 名神经不受影响的父母（父亲或母亲）均为杂合子携带者，表现出小白点状视网膜斑点。所有接受测试的患者均携带 SPG11 突变，而不是 SPG15 突变。
SPG11 突变的神经症状在婴儿期早期出现，表现为行走和语言困难。截瘫始于第一个十年末或第二个十年期间。在截瘫明显出现之前，仅观察到本系列患者的 SPG11 突变的视网膜变化。
