Leber congenital amaurosis (LCA) is a congenital cause of severe visual loss. It is an autosomal recessive condition caused by several different mutations in a variety of genes. It is therefore important to identify the cause of the retinopathy using clinical findings and other diagnostic tests to support the diagnosis. Genetic testing has become mandatory to establish the diagnosis.

The trademarks of LCA are:

• the severe and early loss of visual acuity
• absent or very sluggish pupillary responses
• undetectable or extremely subnormal electroretinogram in both light and dark conditions, which shows the absence of transduction of visual signals from the photoreceptors to the brain
• the presence of the oculodigital sign
• a family history corresponding to that of an autosomal recessive disorder

The absence of eye fixation or oscillation in response to visual stimuli is noted from 6 weeks or more of neonatal life. The retinal examination may yield normal findings, or there may be defects of the macula, pigmentary dystrophy, as well as refractive errors (especially hyperopia), nystagmus and photophobia.

Oculodigital Sign of Franceschetti

This sign is highly suggestive of but not specific to LCA. Children with LCA typically poke, prod or rub their eyes. As a result, the eye may recede into the socket (enophthalmos) because of atrophy of the orbital fat cushion. Again, corneal injury from repeated rubbing may lead to keratoconus (bulging out of the center of the cornea leading to visual impairment), but this has been disputed by others who consider it an intrinsic part of the syndrome.

Vision

Vision is severely affected in LCA, both visual acuity and visual function. The eye in such patients eventually has a vision of 20/400 or less. Some cannot see light at all, others may function at the level of perception of light. Typically, the patient has a stable severe loss of vision, but some have a progressive reduction while others even show some improvement in adolescence or early adulthood. This may be due to mutations occurring in different genes, or because of the maturation of central pathways. The visual loss is due to keratoconus, cataract or progressive macular lesions.

Eye Examination

The most common refractive error seen in this condition is hyperopia, but high myopia has been observed in a few. Photophobia, night blindness, nystagmus, cataract and keratoconus are all features of LCA in different patients. Franceschetti’s oculodigital sign is also typical in this disease. Again, the symptoms may vary with the mutations reported.

Mental Retardation

Whereas earlier reports suggested a high incidence of mental retardation in LCA, over 50%, recent studies employing brain scans to rule out organic pathology has found this to be a gross overestimate. However, these patients show stereotypical movements including rubbing the hands, touching the hair, grimacing, and eye poking. Some report anosmia in both cases and carriers when LCA is associated with the CEP290 gene.

Retinal Features

While the retina is quite normal-appearing at first, several anomalies may be observed to develop later, such as:

• Macular coloboma, or a clearly demarcated gap in the retina, which is due to atrophy of the retina around the fovea (the point where vision is sharpest due to the highest concentration of cone cells), or spots of chorioretinal degeneration, seen especially with NMNAT1, and sometimes with AIPL1 and CRB1 subtypes
• Retinal pigment migrating in various patterns resembling bone spicules
• Subretinal flecks scattered all over the retina
• Marbled appearance of the retina
• Separate pigmented coin-shaped lesions in the retinal pigment epithelium
• Swelling or deposition of protein around the optic disc, with the growth of fragile and disordered new vessels around the disc
• Star-shaped lesions of the macula with a translucent appearance to the retinal pigment epithelium, in the RPE65 subtype
• Normal pigment in the para-arteriolar region, called preserved para-arteriolar retinal pigment epithelium, in the CRB1 subtype