This is an old revision of the document!
Leber Congenital Amaurosis
Main Features
- Congenital or Early infancy non-syndromic retinal blindness
- Searching Nystagmus
- Abnormal pupil reponses
- “oculodigital sign”- digital eye pressure to induce retinal response
- Initially normal fundus appearance followed by pigmentary changes in the retina, vascular attenuation and peripheral pigmentary changes in the retina
- Bone spicules in macula and periphery
- Loss of retinal lamination and photoreceptor loss
- Exudative type retinopathy in CRB1-assoicated disease
- RPE65-related disease usually has milder peripheral RPE mottling and white dots
- Disc drusen or pseudopapilledema
Distinguishing Features
- Severe visual impairment from birth or first few months of life
- Fundus appearance
- may be normal
- Vessel attenuation, disc pallor, peripheral retinal pigmentation
- ERG is undetectable
Differential Dx
- Unordered List Item
Pathogenesis
- 70% of patients have a known genetic variant io one of the following genes that preferentially are expressed in the retina or RPE
- Autosomal Recessive
- AIPL1, ALMS1, CEP290, CRB1 (photoreceptor cell structure), GUCY2D (Protein trafficking), IMPDH1, LCA5, LRAT (visual cycle function), MERTK, RD3 ,RDH12, RPGRIP1, RPE65 (visual cycle function), SPATA7, KCNJ13, ICQB1, NMNAT1, and TULP1
- Autosomal Dominant: CRX - photoreceptor cell development
Treatment
RPE65 Mutations
- Gene replacement therapy with Luxturna (vortigene neparvovec-rzyl)