Alport syndrome anterior lenticonus
The term Alport syndrome encompasses a group of inherited, heterogeneous disorders involving the basement membranes of the kidney and frequently affecting the cochlea and eye as well.
Anterior lenticonus, which occurs in approximately 25% of patients with XLAS, is the pathognomonic feature of Alport syndrome. In this condition, the lens surface protrudes conically into the anterior chamber of the eye because of a thin and fragile basement membrane of the lens capsule. The lenticonus is most marked anteriorly because the capsule is thinnest there, the stresses of accommodation are more marked, and the lens is least supported.
Anterior lenticonus is not present at birth but is manifested by a slowly progressive deterioration of vision, requiring patients to change the prescription of their glasses frequently. The condition is not accompanied by eye pain, redness, or night blindness, and no defect in color vision occurs.
This is the most common ocular manifestation of patients with Alport syndrome, occurring in approximately 85% of males with XLAS. Rarely observed in childhood, it usually becomes apparent at the onset of renal failure. Dot-and-fleck retinopathy is usually asymptomatic, with no associated visual impairment or night blindness.
Posterior polymorphous corneal dystrophy
This condition is rare in Alport syndrome. Most patients are asymptomatic, although some of them may develop slowly progressive visual impairment.
Temporal macular thinning
The L1649R mutation in the COL4A5 gene occasionally causes severe temporal macular thinning, a prominent sign associated with XLAS.
Some authors have considered anterior lenticonus as a manifestation of Alport syndrome, whereas posterior lenticonus is not associated with systemic disease.Others have suggested that posterior lenticonus is a rare manifestation of Alport syndrome.The prevalence of posterior lenticonus is estimated at 1–4 in 100,000 children.
The ocular and clinical features of Alport syndrome are identical in both the X-linked and autosomal recessive forms. Retinopathy and cataracts are the only ocular abnormalities described in the rare autosomal dominant form of Alport syndrome. Previous literature has reported variability in the incidence of ocular manifestations of Alport syndrome. Colville et al. reported dot-and-fleck retinopathy in 85% of affected adult males, anterior lenticonus in approximately 25%, and with posterior polymorphous corneal dystrophy being rare. Chugh et al. reported the prevalence of anterior lenticonus in 37.8% of the subjects, retinal flecks in 22.2%, cataract in 20%, and keratoconus in 6.7% of subjects. Teekhasaenee et al. reported ocular manifestations in 82.3% of subjects with Alport syndrome. Posterior polymorphous dystrophy was the most common manifestation, occurring in 64.7% of subjects. Jacobs et al.reported that ocular changes are uncommon and subtle in young patients with Alport syndrome, and that the signs increase in frequency and severity with age. In our case, both anterior lenticonus and cataract were present. The presence of posterior lenticonus late in the natural history of the syndrome may reflect the progressive nature of this manifestation.
The X-linked mutations have been mapped to defects in the α-5-chain of the type IV collagen gene, compromising the COL4A5, COL4A3, and COL4A4 genes. All mutations lead to abnormalities in the basement membrane of the glomerulus, cochlea, retina, lens capsule, and cornea, which eventually contribute to the typical phenotype of Alport syndrome.Recently, the presence of a complex (core plus secondary) binding site for TCF8 in the promoter of Alport syndrome gene COL4A3, which encodes collagen type IV alpha 3 is thought to cause posterior polymorphous dystrophy.