Colville D J, Savige J
Ophthalmology Unit, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Ophthalmic Genet. 1997 Dec;18(4):161-73. doi: 10.3109/13816819709041431.
Alport syndrome has a prevalence of 1/5000, and 85% of patients have the X-linked form, where affected males develop renal failure and usually have a high-tone sensorineural deafness by the age of 20. The typical ocular associations are a dot-and-fleck retinopathy which occurs in about 85% of affected adult males, anterior lenticonus which occurs in about 25%, and the rare posterior polymorphous corneal dystrophy. The retinopathy and anterior lenticonus are not usually demonstrated in childhood but worsen with time so that the retinal lesion is often present at the onset of renal failure, and the anterior lenticonus, later. The demonstration of a dot-and-fleck retinopathy in any individual with a family history of Alport syndrome or with end-stage renal disease is diagnostic of Alport syndrome. The presence of anterior lenticonus or posterior polymorphous corneal dystrophy in any individual is highly suggestive of the diagnosis of Alport syndrome. Additional ocular features described in X-linked Alport syndrome include other corneal dystrophies, microcornea, arcus, iris atrophy, cataracts, spontaneous lens rupture, spherophakia, posterior lenticonus, a poor macular reflex, fluorescein angiogram hyperfluorescence, electrooculogram and electroretinogram abnormalities, and retinal pigmentation. All mutations demonstrated to date in X-linked Alport syndrome have affected the COL4A5 gene which encodes the alpha 5 chain of type IV collagen. This protein is probably common to the basement membranes of the glomerulus, cochlea, retina, lens capsule, and cornea. However, the alpha 3(IV) and 4(IV) as well as the alpha 5(IV) collagen chains are usually absent from the affected basement membranes, because the abnormal alpha 5(IV) molecule interferes with the stability of all three. The loss of these collagen molecules from the affected basement membranes results in an abnormal ultrastructural appearance. The ocular and other clinical features of autosomal recessive Alport syndrome are identical to those seen in X-linked disease, while retinopathy and cataracts are the only ocular abnormalities described in the rare autosomal dominant form of Alport syndrome. There are no ocular associations of thin basement membrane disease which is a common disease that probably represents the heterozygous expression of X-linked or autosomal recessive Alport syndrome.
奥尔波特综合征的患病率为1/5000，85%的患者为X连锁型，患病男性会发展为肾衰竭，通常在20岁时出现高频感音神经性耳聋。典型的眼部关联表现包括点状和斑点状视网膜病变，约85%的成年男性患者会出现；前圆锥形晶状体，约25%的患者会出现；以及罕见的后多形性角膜营养不良。视网膜病变和前圆锥形晶状体在儿童期通常不会出现，但会随着时间恶化，因此视网膜病变常在肾衰竭发病时出现，前圆锥形晶状体则在之后出现。在有奥尔波特综合征家族史或终末期肾病的个体中，出现点状和斑点状视网膜病变可诊断为奥尔波特综合征。任何个体出现前圆锥形晶状体或后多形性角膜营养不良都高度提示奥尔波特综合征的诊断。X连锁型奥尔波特综合征中描述的其他眼部特征还包括其他角膜营养不良、小角膜、角膜弓、虹膜萎缩、白内障、晶状体自发性破裂、球形晶状体、后圆锥形晶状体、黄斑反射不良、荧光素血管造影高荧光、眼电图和视网膜电图异常以及视网膜色素沉着。迄今为止，在X连锁型奥尔波特综合征中发现的所有突变都影响了编码IV型胶原α5链的COL4A5基因。这种蛋白质可能存在于肾小球、耳蜗、视网膜、晶状体囊和角膜的基底膜中。然而，受影响的基底膜中通常不存在α3(IV)和α4(IV)以及α5(IV)胶原链，因为异常的α5(IV)分子会干扰这三种链的稳定性。这些胶原分子从受影响的基底膜中缺失会导致超微结构外观异常。常染色体隐性奥尔波特综合征的眼部和其他临床特征与X连锁型疾病所见相同，而视网膜病变和白内障是罕见的常染色体显性奥尔波特综合征中描述的仅有的眼部异常。薄基底膜病没有眼部关联表现，薄基底膜病是一种常见疾病，可能代表X连锁或常染色体隐性奥尔波特综合征的杂合表达。
