Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous group of nonprogressive retinal disorders that can be characterized by impaired night vision, decreased visual acuity, nystagmus, myopia, and strabismus. CSNB can be classified into 2 groups ... Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous group of nonprogressive retinal disorders that can be characterized by impaired night vision, decreased visual acuity, nystagmus, myopia, and strabismus. CSNB can be classified into 2 groups based on electroretinography (ERG) findings: the Schubert-Bornschein type is characterized by an ERG in which the b-wave is smaller than the a-wave, whereas the Riggs type is defined by proportionally reduced a- and b-waves. In addition, Schubert-Bornschein CSNB is associated with decreased visual acuity, myopia, and nystagmus, whereas in Riggs CSNB patients have visual acuity within the normal range and no symptoms of myopia and/or nystagmus (summary by Riazuddin et al., 2010). Additionally, Schubert-Bornschein CSNB can be subdivided into 'complete' and 'incomplete' forms (summary by Riazuddin et al., 2010). Van Genderen et al. (2009) noted that standard flash ERG distinguishes a 'complete' form, also known as type 1 CSNB, from an 'incomplete' form, also known as type 2 CSNB (see CSNB2A, 300071). The complete form is characterized by the complete absence of rod pathway function, whereas the incomplete form is due to impaired rod and cone pathway function. Complete CSNB results from postsynaptic defects in depolarizing or ON bipolar cell signaling, whereas the hyperpolarizing or OFF bipolar cell pathway is intact. - Genetic Heterogeneity of Congenital Stationary Night Blindness Autosomal recessive forms of complete CSNB have been reported: CSNB1B (257270), caused by mutation in the GRM6 gene (604096); CSNB1C (613216), caused by mutation in the TRPM1 gene (603576); CSNB1D (613830), caused by mutation in the SLC24A1 gene (603617); and CSNB1E (614565), caused by mutation in the GPR179 gene (614515). Autosomal dominant forms of complete CSNB that have been reported include CSNBAD1 (610445), caused by mutation in the RHO gene (180380); CSNBAD2 (163500), caused by mutation in the PDE6B gene (180072); and CSNBAD3 (610444), caused by mutation in the GNAT1 gene (139330). In addition, X-linked and autosomal recessive forms of incomplete CSNB have been reported: CSNB2A (300071), caused by mutation in the CACNA1F gene (300110); and CSNB2B (610427), caused by mutation in the CABP4 gene (608965). A form of autosomal recessive CSNB in which all other visual functions are normal is designated Oguchi disease: Oguchi type 1 (258100) is caused by mutation in the SAG gene (181031), and Oguchi type 2 (613411) is caused by mutation in the RHOK gene (GRK1; 180381).
Night blindness is a symptom of several chorioretinal degenerations. (According to the interpretation of some, particularly French-speaking writers, nyctalopia means literally 'seeing at night' and hemeralopia means 'seeing in the day;' hence, nyctalopia is 'dayblindness,' e.g., total colorblindness ... Night blindness is a symptom of several chorioretinal degenerations. (According to the interpretation of some, particularly French-speaking writers, nyctalopia means literally 'seeing at night' and hemeralopia means 'seeing in the day;' hence, nyctalopia is 'dayblindness,' e.g., total colorblindness (216900), and hemeralopia is 'night blindness.' See later for a discussion of the derivation of these 2 terms, including the idea that the syllable 'al,' coming from a Greek root for 'blind' or 'obscure,' actually makes nyctalopia mean night blindness.) The distinctive feature of the mutation listed here is the stationary nature of the night blindness. There is an autosomal dominant variety reported in many families, of which the most famous is that descendant from Jean Nougaret, born in Provence in 1637, and studied by Cunier (1838), Nettleship (1909, 1912) and others (see 610444). The X-linked form is distinguished from the autosomal form by the association of myopia. Morton (1893) described a family with X-linked myopia and night blindness. Fraser and Friedmann (1967) described a family from the same area near Cardiff, Wales. Myopia also occurs with external ophthalmoplegia (311000) and possibly as an uncomplicated X-linked recessive (310460). Worth (1906) reported 4 families with myopia which apparently was X-linked. At Nettleship's suggestion, he looked for associated night blindness and found it in the affected members of only 1 of the families. In Oswald's family with myopia transmitted in a pattern otherwise consistent with X-linked inheritance, apparent male-to-male transmission occurred in the first generation. Francois and De Rouck (1965) described 2 families with 'degenerative' myopia transmitted as an X-linked recessive. In 1 of the families congenital hemeralopia was associated. Scotopic vision is abnormal in this disorder from a putative defect in neurotransmission from photoreceptors to middle retinal neurons. Moro et al. (1982) described a large 4-generation Sicilian family segregating severe myopia associated with nyctalopia as an X-linked trait. The authors noted that night blindness was present in all 4 affected family members in whom it was sought and stated that it 'probably also existed' in the other 11 patients. Exotropia, esotropia, and hypertropia were also observed in affected individuals who underwent examination. Miyake et al. (1986) suggested that congenital stationary night blindness can be divided into 2 types, which they called 'complete' and 'incomplete.' In the complete type, rod function is absent, whereas in the incomplete type, there is residual, recordable rod function. Complete and incomplete types did not occur within the same pedigree (Miyake et al., 1986). Khouri et al. (1988), however, reported a family in which 3 of 5 affected members had hyperopia and could be classified as incomplete type, while a fourth member with myopia was more consistent with the complete type. They repeated the suggestion that the association between myopia and night blindness is 'consistent with close linkage of the genes coding for these 2 traits on the X chromosome.' In fact, the great rarity of X-linked night blindness without myopia makes the explanation of linkage unlikely. Furthermore, their explanation for the occurrence of both myopia and hyperopia in the same family, i.e., a crossing-over between 2 genes, seems unlikely. Another suggestion they made seems more likely, namely, that 'an autosomal dominant hyperopic gene masked the myopic gene.' Musarella et al. (1989) studied 7 multigeneration families with complete congenital stationary night blindness (symbolized CSNB1) and 1 family with the incomplete disorder (CSNB2; see 300071). In general, X-linked congenital stationary night blindness is a nonprogressive retinal disorder resulting from a presumptive defect of neurotransmission between the photoreceptors and the bipolar cells. The complete form lacks rod function by ERG and dark adaptometry and is accompanied by refractive error ranging from mild to severe myopia. The incomplete type shows some rod function on scotopic testing and is accompanied by refraction ranging from moderate hyperopia to moderate myopia.
In a study of a large Mennonite family with CSNB1, Bech-Hansen and Pearce (1993) found that 3 of 5 sisters in 1 sibship had typical manifestations of the disorder. All of the sons of these 3 sisters were ... In a study of a large Mennonite family with CSNB1, Bech-Hansen and Pearce (1993) found that 3 of 5 sisters in 1 sibship had typical manifestations of the disorder. All of the sons of these 3 sisters were affected. Each of the 2 nonmanifesting sisters had at least 1 unaffected son. Analysis of Xp markers in the Xp21.1-p11.22 region showed that the 2 sisters who were unaffected had inherited the same maternal X chromosome, designated M2. Two of the daughters who manifested CSNB had inherited the other maternal X chromosome, designated M1. The third manifesting sister inherited a recombinant X chromosome with a crossover between TIMP and DXS255, which suggested that the CSNB1 locus lies proximal to TIMP, a conclusion contrary to one mentioned earlier. One of the affected daughters' sons had inherited the maternal M1 X chromosome, a finding consistent with that chromosome carrying a mutant CSNB gene; the other affected sons inherited the grandfather's X chromosome, thus supporting homozygosity of the mothers. Molecular analysis of DNA from the 3 sisters with manifestations of CSNB yielded results consistent with their being homozygous and with their mother being a carrier of CSNB1. Bech-Hansen et al. (1998) subsequently identified a frameshift mutation in exon 27 of the CACNA1F gene in 15 different families with incomplete CSNB (CSNB2; 300071); these 15 families were established by haplotype analysis to be related by a founder effect (Boycott et al., 1998; see 300110.0003). Bech-Hansen et al. (2000) studied 22 families with X-linked complete CSNB in which affected males have night blindness, some photopic vision loss, and a defect of the ON-pathway. They found 14 different mutations, including 1 founder mutation, in 7 families from the United States, in a novel candidate gene, NYX (300278). NYX, which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a unique member of the small leucine-rich proteoglycan (SLRP) family. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolor cells, leading to the visual losses seen in patients with complete CSNB. NYX was the second member of the SLRP family to be associated with a human genetic disease. Keratocan (KERA; 603228) had been identified as the cause of autosomal recessive cornea plana. Pusch et al. (2000) identified mutations in the NYX gene in patients with CSNB1. The gene was partially deleted in 3 families, and mutation analysis in 21 further families detected another 13 different mutations. They found the NYX gene to be expressed at low levels in tissues including retina, brain, testis, and muscle. In affected members from 2 unrelated Chinese families with X-linked congenital stationary night blindness and high myopia, Xiao et al. (2006) identified 2 different mutations in the NYX gene (300278.0005; 300278.0006).