Onset and clinical features

LCA typically becomes evident in the first year of life with poor visual function often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia, and keratoconus. Profound visual impairment (generally stable or very slowly progressive) is usually present from birth. The oculo-digital sign (poking, rubbing, and/or pressing of the eyes) is claimed to be virtually pathognomonic for LCA though it can be seen in other syndromic forms of severe vision impairment. The electroretinogram (ERG) is characteristically "nondetectable" or severely abnormal. The retinal findings are not specific: fundus is either normal, or only subtle retinal pigment epithelial (RPE) granularity and retinal vessel attenuation can be observed (Figure 1). LCA is currently considered to be the most severe retinal dystrophy without major systemic features. In rare cases, LCA is associated with neurodevelopmental delay and intellectual disability. Olfactory dysfunction in LCA patients with CEP290 mutations has also been described.