Expanding the Phenotypic and Genotypic Spectrum of Bietti Crystalline Dystrophy

Abstract

The rare form of retinal dystrophy, Bietti crystalline dystrophy, is associated with variations in CYP4V2, a member of the cytochrome P450 family. This study reports patients affected by typical and atypical Bietti crystalline dystrophy, expanding the spectrum of this disease. This is an observational case series of patients with a clinical and molecular diagnosis of Bietti crystalline dystrophy that underwent multimodal imaging. Four unrelated patients are described with two known variants, c.802-8_810del17insGC and c.518T > G (p.Leu173Trp), and one novel missense variant, c.1169G > T (p.Arg390Leu). The patient with the novel homozygous variant had the most severe phenotype resulting in macular hole formation and retinal detachment in both eyes. To the best of our knowledge, there is no association of these features with Bietti crystalline dystrophy. Patient 1 was the youngest patient and had the mildest phenotype with crystals in the retina without chorioretinal atrophy and visual complaints. Patients 2 and 3 presented with fewer crystals and chorioretinal atrophy. These three patients presented a classic phenotype. The fourth patient presented with an atypical and severe phenotype. This study reveals a new genotype and new phenotype associated with this disorder.

Structural and functional phenotypic features and molecular analysis of Indian patients with Bietti crystalline dystrophy

“…BCD shows a wide phenotypic variation, and the majority of authors have not been able to establish an accurate correlation between the genotypes and phenotypes. [ 4 5 11 12 ] Halford et al . [ 13 ] noted that the mutation p.Met66Arg was associated with earlier age of onset at around 30 years.…”

“…The limbal corneal crystals are very fine and often very subtle and therefore are likely to be missed even by experienced specialists. [ 1 4 ] However, it is also noted by some authors that the corneal crystals are absent in Asian populations but more commonly seen in Caucasian populations. [ 15 19 ] The CYP4V2 coded protein is less expressed in the corneal epithelium than the RPE.…”

“…At this stage, it can be confused with other flecked retina syndromes, retinitis punctate albescens, reticular pseudodrusen, or cystinosis. [ 4 ] As the disease progresses, the crystalline deposits disappear and severe chorioretinal atrophy occurs. At this stage, it can resemble other retinal degenerations such as retinitis pigmentosa, choroideremia, or gyrate atrophy.…”

“…The protein encoded by this gene is a member of the cytochrome P450 family. [ 4 ] They are thought to be essential for lipid recycling between the RPE and photoreceptor outer segments as a part of the visual cycle. This gene is also expressed in various other organs such as the lungs, liver, brain, kidneys, heart, placenta, and lymphocytes.…”

“…BCD is increasingly being described in populations other than the Chinese, such as the Japanese, Spanish, Middle Eastern, Brazilian, and Nepalese. [ 1 4 ] There are a few isolated case reports from the Indian population as well. [ 6 7 ] This is the largest study so far reported from the Indian population.…”