Bietti crystalline dystrophy (BCD) is a chorioretinal degeneration characterized by the presence of yellow-white crystals and/or complex lipid deposits in the retina and (to a variable degree) the cornea. Progressive atrophy and degeneration of the retinal pigment epithelium (RPE) / choroid lead to symptoms similar to those of other forms of retinal degeneration that fall under the category of retinitis pigmentosa and allied disorders, namely: reduced visual acuity, poor night vision, abnormal retinal electrophysiology, visual field loss, and often impaired color vision. Marked asymmetry between eyes is not uncommon. Onset is typically during the second to third decade of life, but ranges from the early teenage years to beyond the third decade. With time, loss of peripheral visual field, central acuity, or both result in legal blindness in most if not all affected individuals.

Optic atrophy-9 (OPA9) is characterized by onset of decreased visual acuity and optic disc pallor in the first decade of life, with severely reduced visual acuity and color vision deficits observed in the third decade. Although initially described as an autosomal recessive disease (Metodiev et al., 2014; Kelman et al., 2018; Gibson et al., 2020), autosomal dominant cases of OPA9 have also been reported (Charif et al., 2021). Mutation in the ACO2 gene also causes a neurodegenerative disorder, infantile cerebellar-retinal degeneration (ICRD; 614559), of which optic atrophy is a feature. Dominant and Recessive OPA9 From a cohort of approximately 1,000 patients with optic atrophy, Charif et al. (2021) identified 50 probands with dominant mutations in the ACO2 gene, and 11 patients with biallelic variants. There was no significant difference in distribution of mutation type, with two-thirds of all variants being missense mutations in both groups, and nonsense, frameshift, and splice site mutations comprising the remaining third. Age at onset of symptoms occurred during the first 2 decades, without significant difference between dominant and recessive cases. Visual acuity was significantly more affected in recessive cases than in dominant ones, with more than 60% of eyes from the recessive group having a visual acuity lower than 20/200, whereas more than 80% of eyes from the dominant group had a visual acuity above 20/200. Analysis of the optic disc as well as retinal nerve fiber layer thickness measurements indicated a preferential involvement of the temporal quadrant in both patient groups. Assessment of color vision revealed highly variable alterations, including protan, deutan, and tritan types of dyschromatopsia. Some patients had additional retinal changes, including macular microcysts as well as macular dystrophy in 1 case. Extraocular symptoms were observed in 6 (12%) of the dominant cases and in 3 (27%) of the recessive cases, including hearing impairment in 2 dominant cases, and late-onset cerebellar ataxia in 1 dominant case and in 1 recessive case.

Retinitis pigmentosa-92 (RP92) is characterized by relatively mild disease, with onset of night blindness and vision loss in the third to sixth decades of life. Patients show abnormal pigmentation of the retina and have reduced scotopic responses on electroretinography (Zhang et al., 2018). For a general phenotypic description and discussion of genetic heterogeneity of RP, see 268000.

Chromosome 16q12 duplication syndrome is characterized by early-onset progressive cone dystrophy, with early blue cone involvement. Patients report reduced visual acuity in the first decade of life, as well as difficulty differentiating colors, photophobia, and reduced night vision (Kohl et al., 2021). Tritanopia can also be caused by heterozygous mutation in the OPN1SW gene (613522) on chromosome 7q32 (see 190900).