Night Blindness, Congenital Stationary, Type 1b

A number sign (#) is used with this entry because congenital stationary night blindness type 1B is caused by mutation in the GRM6 gene (604096) on chromosome 5q35.

For a general phenotypic description and discussion of the genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500).

Clinical Features

Gassler (1925) constructed an instructive pedigree of an inbred Swiss kindred with night blindness and myopia which was reproduced by Francois (1961). Merin et al. (1970) and Der Kaloustian and Baghdassarian (1972) reported instructive families. Weleber and Tongue (1987) emphasized the possible confusion of autosomal recessive congenital stationary night blindness with Leber congenital amaurosis (see 204000).

Barnes et al. (2002) reported a 30-year-old Greek man with a history of night blindness. There was no known consanguinity, although his parents were from the same village in Greece. The patient's maximal dark-adapted response showed both a reduced a-wave and a markedly reduced b-wave as compared with that of a control individual. There was substantial reduction in a-wave amplitude, in contrast to CSNB1A (310500), in which little or no reduction in the amplitude of the ERG a-wave is seen (Miyake et al., 1986). Barnes et al. (2002) also noted that the patient's pedigree did not appear to be consistent with X-linked inheritance and the patient did not show the reduced visual acuity and myopia that are common in CSNB1A. The patient's mother had a severe retinitis pigmentosa (RP, see 268000)-like condition, but the diagnosis of a mild form of RP in the proband was ruled out because of the entirely normal appearance of the fundus at age 30 and the lack of other visual changes over time, such as peripheral visual field loss. Barnes et al. (2002) concluded that the overall pattern of findings distinguished this patient from previously described forms of CSNB. They suggested that 2 factors, a rod phototransduction defect and a postreceptoral defect, are likely to contribute to his night blindness, and also noted evidence of dysfunction within the cone ON pathway.

Dryja et al. (2005) reexamined the patient reported by Barnes et al. (2002) at 37 years of age, at which time the patient reported that there had been no worsening of his night blindness. He had developed sparse midperipheral bone spicule-shaped pigment clumps, primarily in the nasal retina, and there was a temporal visual field defect that had not been apparent on his initial examination. ERGs to elicit cone ON and OFF responses showed prominent and normal a-waves but substantially reduced b-waves in the ON responses. Dryja et al. (2005) suggested that the signs of retinal degeneration in this patient might be related to his being a carrier of a mutation in an unidentified RP gene, since his mother had an apparently autosomal recessive form of RP. The authors also reported 2 other patients who had been night-blind from an early age. All 3 patients had visual acuities that were normal or only slightly reduced. When maximally dark-adapted, they could perceive lights only with an intensity 2 to 3 log units above normal.

Abramowicz et al. (2005) described a son and daughter, born of first-cousin parents, with complete stationary night blindness. They considered several candidate genes and excluded the sidekick genes SDK1 (607216) and SDK2 (607217).

Zeitz et al. (2005) reported 5 individuals with CSNB1B from 3 unrelated families. All patients displayed a distinctive abnormality of the rod pathway signals on scotopic 15-Hz flicker ERG, characterized by abnormal phase behavior with several minimum responses.

Molecular Genetics

Dryja et al. (2005) analyzed the GRM6 gene (604096) in 26 unrelated patients with a prior diagnosis of congenital stationary night blindness. A 37-year-old Greek man, previously reported by Barnes et al. (2002), was found be homozygous for a nonsense mutation (604096.0001). A 14-year-old girl was homozygous for a missense mutation (604096.0002), and a 31-year-old man was compound heterozygous for a nonsense mutation (604096.0003) and a missense mutation (604096.0004).

In affected members of 3 unrelated families with CSNB1B, Zeitz et al. (2005) identified 5 different homozygous or compound heterozygous mutations in the GRM6 gene (see, e.g., 604096.0005-604096.0007).

Nomenclature

The term nyctalopia, which literally means 'seeing at night,' is a misnomer. Hemeralopia ('seeing in the day') is the proper term for night blindness. See 310500 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.