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--- congenital_stationary_night_blindness [2025/11/25 18:21] – Scott Larson
+++ congenital_stationary_night_blindness [2025/12/01 15:52] (current) – Scott Larson
@@ Line 1: / Line 1: @@
 ====== Congenital Stationary Night Blindness ======
+====Main Features====
+  * Night Blindness, variable vision loss, largely normal fundus
+  * May have nystagmus and strabismus
+====Distinguishing Features=====
+  * Night blindness
+  * Normal Appearing Fundus
+  * High Myopia
+    * may have tilted discs and nerve pallor
+  * ERG
+    * "Negative ERG"
+      * Photoreceptor derived a-wave with a bright flash is normal
+      * Reduction of the inner nuclear derived b-wave from inner retinal dysfunction
+    * No detectable Rod specific ERG- dark adapted dim flash
-====== Leber Congenital Amaurosis ======
+<WRAP round box 100%>
-First described in 1869 by Theodore Leber.
+Figure 45.2 Taylor and Hoyt
+{{::csnb_erg_responses.jpg|}}
+Congenital stationary night blindness. The left-hand column traces (A) show data from a patient with “incomplete” CSNB (iCSNB); the center traces (B) are from a patient with “complete” CSNB (cCSNB); the right-hand column traces (C) are from a representative normal subject. In iCSNB the rod ERG (DA 0.01) is mildly subnormal. The bright flash response (DA 10.0) is electronegative, with a normal a-wave confirming normal photoreceptor function, but a profoundly reduced b-wave. The 30 Hz flicker ERG (LA 30 Hz) is markedly subnormal and clearly shows the delayed double peak characteristically seen in iCSNB. The photopic single flash ERG (LA 3.0) shows marked reduction in the b:a ratio with simplification of the waveform and loss of the photopic oscillatory potentials, shown on ON/OFF response recording (200 ms orange stimulus on a green background) to reflect involvement of both ON (depolarizing) and OFF (hyperpolarizing) cone bipolar cell pathways. The pattern electroretinogram (PERG) is mildly subnormal in keeping with mild macular dysfunction. In cCSNB there is no detectable DA 0.01 response and the profoundly electronegative DA 10.0 ERG confirms the site of the dysfunction to be post-phototransduction. The LA 3.0 response shows a distinctive broadened a-wave and a sharply rising b-wave with a reduced b:a ratio and lack of photopic oscillatory potentials. This appearance indicates marked dysfunction of cone ON bipolar cell pathways but preservation of the OFF pathways. The profoundly negative ON response, with preservation of the ON a-wave and loss of the ON b-wave, accompanied by a normal OFF response is confirmatory. The broadened trough of the 30 Hz flicker ERG with a sharply rising peak is a manifestation of the same phenomenon. The PERG is almost undetectable. Overall, the findings in cCSNB are those of loss of ON pathway function in both rod and cone systems.  Michel Michaelides; Graham E Holder; Anthony T Moore, 45, 526-549
+</WRAP>
-====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]]
@@ Line 28: / Line 26: @@
   * Idiopathic Nystagmus Syndrome
 ====Pathogenesis====
+  * Autosomal Dominant
+    * Genes that affect rod-specific phototransduction (RHO, GNAT1 , cGMP, PDE6β)
+    * Normal or mildly reduced visual acuity
+  * Autosomal recessive
+    * Biallelic disease causing variants of GRM6, TRPM1, GPR179 or LRIT3 which are all involved in photoreceptor-bipolar cell synaptic development or function.
+    * Variants of CABP4,  a calcium binding protein
+      * Associated with "incomplete" forms of the disease
+    * Variants in the SLC24A1 gene
+      * give CSNB without a negative ERG response. Both a- and b-waves are equally reduced
+      * SLC24A1 is a member of the solute carrier protein superfamily located in inner segments, outer and inner nuclear layers, and ganglion cells
+    * Mild to moderate central vision loss
+    * Nystagmus and strabismus
+  * X-Linked
+    * CACNA1F gene mutations
+      * encodes retina specific subunit of voltage-gated L-type calcium channel
+      * involved in "incomplete" forms of the disease
+    * NYX gene mutations
+      * encodes leucine-rich proteoglycan nyctalopin which is expressed in photoreceptor inner segments, outer and inner nuclear layers and ganglion cells.
+      * Involved in the "complete" forms of the disease
+    * Mild to moderate central vision loss
+    * Nystagmus , strabismus
 ====Treatment====
-===RPE65 Mutations===
+  * Low vision and adaptive strategies
-  * Gene replacement therapy with [[https://luxturna.com|Luxturna]] (vortigene neparvovec-rzyl)
+  * Future hopes of Gene Therapy see reference 2 below
-    * 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.]]
+  - [[https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780702082986000457#hl0000441|Taylor and Hoyt chapter 46. Stationary Night Blindness.]]
+  - [[https://link.springer.com/article/10.1186/s12967-025-06392-8 |Yi Zhang et al. Gene therapy shines light on congenital stationary night blindness for future cures. Journal of Translational Medicine 2025;23 article 392]]
-{{tag>inherited_retinal_disease retina}}
 {{tag>inherited_retinal_disease retina}}

inherited retinal disease retina