OMIM ID:
Night Blindness, Congenital Stationary, CSNB2A
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive. However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB). At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them. All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves. However, the photopic ERG can be abnormal to some degree as well and visual acuity may be subnormal. In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB. Genotyping now enables classification with unprecedented precision.
Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision. Nystagmus and photophobia are usually not features. Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies. The amount of pigmentary retinopathy is highly variable.
CSNB2A, or type 2A, is associated with myopia which ranges from mild to severe. Residual rod function is diminished but not completely absent as suggested by the presence of small b-waves. Cone function is impacted to some degree as well. Nystagmus and strabismus are inconsistent findings. Retinal pigmentation is usually normal in the X-linked forms. Visual acuity ranges from 20/30 to 20/200. Night blindness is less severe in this form than in another X-linked CSNB (CSNB1A; 310500). Mild dyschromatopsia is present in some patients but this is primarily a disease of rods.
Systemic Features
No systemic disease is associated with congenital stationary night blindness.
Genetics
Inheritance
Congenital stationary night blindness type 2A is an X-linked disorder caused by a mutation in the CACNA1F gene located at Xp11.23. Only males are affected and carrier females do not have clinical disease.
This disorder is allelic to Aland Island Eye Disease (300600) from which it differs by an apparent lack of progressive myopia and the presence of a normal fovea. Aland Island Eye Disease has foveal hypoplasia as well as iris and fundus hypopigmentation.
Another allelic disorder with mutations in CACNA1F is CORDX3 (300476), a cone-rod dystrophy.
Approximately 55% of X-linked CSNB are of this type while about 45% have another X-linked form known as CSNB1A, or type 1A (310500) secondary to a mutation at Xp11.4.
Pedigree
X-linked recessive, carrier mother
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked recessive, father affected
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.