Night Blindness, Congenital Stationary, Autosomal Dominant 1

A number sign (#) is used with this entry because a form of autosomal dominant congenital stationary night blindness is caused by mutations in the gene encoding rhodopsin (RHO; 180380). Other forms of autosomal dominant CSNB can be caused by mutation in the PDE6B gene (180072) on chromosome 4p16 and the GNAT1 gene (139330) on chromosome 3p21.

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

Clinical Features

Sieving et al. (1992) studied a large Michigan kindred with no detectable rod vision. Despite the absence of detectable rod function, cone electroretinography (ERG) amplitudes were normal in 5 and only partially reduced in 2 other older individuals. The oldest affected individual showed reduced amplitude responses to both single-flash and 30-Hz flickers. Fundus reflectrometry in the 38-year-old proband showed normal rhodopsin density. Two of the patients, aged 38 and 64 years, also demonstrated peripheral retinal pigmentary changes associated with visual field loss. In view of this finding, the authors hesitated to classify the condition as 'stationary.' Older members of the family showed bone-spicule pigmentation, mild diffuse atrophy of the retinal pigment epithelium, and narrowed retinal vessels. Although the 38-year-old proband in this family could not perceive dim lights, his rod increment threshold function was normal on brighter backgrounds (Sieving et al., 1995). The impaired rod vision for dim but not bright backgrounds is consistent with the mechanism of increased basal 'dark-light' from thermal isomerization equivalent to an increase of more than 10,000 times over that of wildtype rhodopsin.

Dryja et al. (1993) reported a simplex patient with congenital stationary night blindness. The patient showed nonrecordable rod responses, reduced amplitude responses to white flashes with shortened implicit times, and borderline normal 30-Hz flickers. Pedigree analysis was impossible. Ophthalmologic examinations at ages 18 and 34 years showed normal fundi. ERGs were identical at the 2 visits and showed absent rod a- and b-waves. Since the patient had no detectable rod b-waves at age 18, and because the cone b-waves were normal in amplitude and implicit time and were unchanged during the 16-year interval between the 2 examinations, the diagnosis of stationary night blindness rather than RP was made.

Al-Jandal et al. (1999) described an Irish family segregating autosomal dominant congenital stationary night blindness. They had ascertained independently 2 nuclear families; pedigree analysis uncovered a relationship between these 2 families and a large 4-generation lineage was established. All individuals questioned reported night vision difficulties for as long as they could remember. None had noted any subjective deterioration over time. Older affected individuals felt safe driving at night in well-lit urban environments. One patient, living in a rural area, was comfortable driving at night under full headlights. No patients reported any subjective problems with day vision. No rod-isolated responses could be recorded in any of the patients, whereas cone-derived ERG responses were entirely normal. Maximal dark-adapted responses showed a similar reduction in a-wave and b-wave amplitudes and marked acceleration of the b-wave implicit times, suggesting that these waveforms may be cone-derived.

Molecular Genetics

In the large kindred reported by Sieving et al. (1992, 1995) the abnormality cosegregated in autosomal dominant fashion with a single-base substitution in codon 90 of rhodopsin: gly90 to asp (180380.0032).

Reasoning that cases of congenital stationary night blindness without a rod a-wave might have a defect in the phototransduction pathway, Dryja et al. (1993) screened leukocyte DNA from 2 unrelated patients for mutations in the coding region of the rhodopsin gene. One, a member of the famous Nougaret kindred (see 610444), had no detectable abnormality. The other, a 34-year-old male who reported night blindness since early life, was heterozygous for a missense mutation, ala292 to glu (A292E; 180380.0031).

Al-Jandal et al. (1999) found a thr94-to-ile mutation in the RHO gene (180380.0042) in an Irish family segregating an autosomal dominant form of CSNB.

Nomenclature

Bordley (1908) discussed the confusion of the terms hemeralopia and nyctalopia, and recommended use of the term night blindness. (Nyctalopia means literally 'seeing at night' and hemeralopia means 'seeing in the day;' hence, nyctalopia is 'day blindness,' e.g., total colorblindness (216900), and hemeralopia is '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.)

History

Bordley (1908) described a black family with typical dominant inheritance of night blindness. There were curious features. All of 7 affected members of different ages and different branches of the family showed abnormal fields of vision, including complete loss of the outer lower quadrants bilaterally. Also the defect could not be said to be stationary: 'as these people grow older their visual fields, even in bright daylight, becomes more and more constricted, until finally they become totally blind. Shortly after they lose their sight they die. Indeed total blindness is looked upon in the family as a infallible sign of impending dissolution....After blindness ensues, the corneae ulcerate and the eyes become infected and are lost.'

Francois et al. (1965) observed a family with at least 4 affected members, all females, in 3 generations.