Ciliopathy: Leber congenital amaurosis

Leber’s congenital amaurosis (LCA), one of the most severe inherited retinal dystrophies, is typically associated with extremely early onset of visual loss, nystagmus, and amaurotic pupils, and is responsible for 20% of childhood blindness. With advances in molecular diagnostic technology, the knowledge about the genetic background of LCA has expanded widely, while disease-causing variants have been identified in 38 genes. Different pathogenetic mechanisms have been found among these varieties of genetic mutations, all of which result in the dysfunction or absence of their encoded proteins participating in the visual cycle. Hence, the clinical phenotypes also exhibit extensive heterogenicity, including the course of visual impairment, involvement of the macular area, alteration in retinal structure, and residual function of the diseased photoreceptor. Typically, patients with LCA present with poor vision and nystagmus or the absence of fixation at as early as 6 weeks of age. Manifestation of vision loss in patients with LCA ranges from functional visual acuity to light perception only, and approximately three-quarters of these are stationary. Transient fluctuation in vision with delayed visual maturation is occasionally observed in the first or second decade of life until progressive decline occurs. The most commonly presented refractive error is hyperopia, especially with the GUCY2D mutation. The patient may present with photophobia or nyctalopia, which could be gene specific. Similar to the presentation of other diseases resulting in congenital blindness, oculodigital signs are common in patients with LCA. Keratoconus and juvenile cataracts are other associated ocular features. Mental retardation could be concurrent in about one-fifth of syndromic or non-syndromic LCA cases. Renal and olfactory dysfunction may be present and are associated with mutations in specific genes.(PMID: 34440435)

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