====== Leber Congenital Amaurosis ======
First described in 1869 by Theodore Leber. 

====Main Features====
  * Congenital or Early infancy non-syndromic retinal blindness
  * Searching nystagmus
  * Abnormal pupil reponses 
  * "oculodigital sign"- digital eye pressure to induce retinal response
  * Fundus appearance: 
    * Initially can have normal fundus appearance followed by pigmentary changes in the retina, vascular attenuation and optic nerve pallor. 
    * 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====
  * [[achromatopsia|Achromatopsia]]
  * [[congenital_stationary_night_blindness|Congenital Stationary Night Blindness]]
  * [[retinitis_pigmentosa|Retinitis Pigmentosa]]
  * Idiopathic Nystagmus Syndrome 
====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 [[https://luxturna.com|Luxturna]] (vortigene neparvovec-rzyl)
    * Adeno-associated virus vector administered subretinally 
====Resources====
  - [[https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780702082986000457#hl0000826|Taylor and Hoyt chapter 46. Leger congenital amaurosis.]]

{{tag>inherited_retinal_disease retina}}