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】阿尔斯特伦综合征（Alström syndrome）是一种罕见遗传病，以ALMS1基因（ALMS1）突变为特征，临床表现为儿童肥胖症、糖尿病、扩张型心肌病、感音神经性听力损失及进行性锥杆营养不良（cone-rod dystrophy），该病可导致失明。该病眼部表现出现于生命最初十年，患者可出现眼球震颤、眼睑痉挛及畏光，进而导致视力进行性严重下降。本研究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描述，检测手段包括光学相干断层扫描（OCT）、眼底自发荧光（fundus autofluorescence）及全视野视网膜电图（full-field electroretinography）。研究发现形态学与功能学检测结果存在相关性，谱域光学相干断层扫描（spectral domain-OCT）与电生理分析中可见视网膜营养不良的典型眼底镜下改变，可证实这一关联。黄斑中心凹特征表现为单层未分化感光细胞伴视网膜结构紊乱，病变主要累及感光细胞外节段，与既往文献报道一致。眼底自发荧光可见高自发荧光区域夹杂低自发荧光斑点，分别提示黄斑区视网膜色素上皮细胞（retinal pigmented epithelial cells）受累与萎缩。视网膜电图分析显示，视锥细胞功能障碍早发，随后视杆细胞快速退变。