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leber_congenital_amaurosis [2025/11/12 15:25] Scott Larsonleber_congenital_amaurosis [2025/11/25 18:19] (current) – [Differential Dx] Scott Larson
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 ====== Leber Congenital Amaurosis ====== ====== Leber Congenital Amaurosis ======
 +First described in 1869 by Theodore Leber. 
  
-FIXME+====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}} {{tag>inherited_retinal_disease retina}}