Morphological and functional findings in Alström syndrome: a study of two families

ABSTRACT Alström syndrome is a rare disorder characterized by mutations to the ALMS1 gene and clinical findings of childhood obesity, diabetes mellitus, dilated cardiomyopathy, sensorineural hearing loss, and progressive cone-rod dystrophy, which may result in blindness. Ocular manifestations occur in the first decade of life with nystagmus, blepharospasm, and photophobia leading to progressive and severe reductions in visual acuity. This study describes the retinal structure and functional aspects of four patients (8 eyes) from two different families as determined by optical coherence tomography (OCT), fundus autofluorescence, and full-field electroretinography. There was a correlation between morphological and functional findings, evidenced by typical funduscopic changes of retinal dystrophy in spectral domain-OCT and electrophysiological analyses. Foveal characteristics include a single layer of undifferentiated photoreceptors with retinal disorganization mainly from external segments, in agreement with previous reports in the literature. Fundus autofluorescence showed areas of hyperautofluorescence interspersed by hypoautofluorescence dots suggesting, respectively, involvement and atrophy of retinal pigmented epithelial cells in the macular zone. Electroretinographic analyses showed early dysfunction of the cones followed by rapid rod deterioration.

【摘要】奥尔斯特伦综合征（Alström syndrome）是一种罕见遗传病，以ALMS1基因突变以及一系列临床特征为典型表现：儿童期肥胖、糖尿病、扩张型心肌病、感音神经性听力损失，以及可导致失明的进行性锥杆营养不良。眼部表现在人生第一个十年即可出现，表现为眼球震颤、眼睑痉挛、畏光，进而引发视力进行性大幅下降。本研究通过光学相干断层扫描（optical coherence tomography, OCT）、眼底自发荧光检查以及全视野视网膜电图检测，对来自两个不同家系的4名患者（共8只患眼）的视网膜结构与功能特征进行了分析。形态学与功能学检查结果存在相关性：光谱域-OCT检查可见视网膜营养不良的典型眼底镜下改变，电生理分析也验证了这一点。中心凹的特征表现为单层未分化感光细胞，且视网膜结构紊乱主要起源于感光细胞外节，这与既往文献报道结果一致。眼底自发荧光检查可见高自发荧光区域散在分布低自发荧光小点，分别提示黄斑区视网膜色素上皮细胞受累与萎缩。视网膜电图分析显示，锥体细胞功能障碍出现较早，随后杆体细胞功能迅速恶化。