Identification of novel CYP4V2 genotypes associated with Bietti crystalline dystrophy and atypical anterior segment phenotypes in Spanish patients

Abstract

To the best of our knowledge, this study represents the largest effort to determine the genetic alterations underlying BCD in Spain to date. Our results show that analysis of CYP4V2 variants is required for a reliable diagnosis of BCD. We report a high prevalence of anterior segment changes in this Spanish BCD cohort, which we consider representative of the Spanish patients.

<p>Current perspectives in Bietti crystalline dystrophy</p>

“…In vivo corneal confocal microscopy has corroborated the location of crystalline deposits in several patients with a previous slit-lamp diagnosis of BCD marginal keratopathy 11,19,20. Corneal dots were detected in the 360º of the peripheral and paracentral cornea, near the limbus, involving subepithelial and anterior stromal layers (approximately 20–40 µm long and 4–8 µm wide), with variable forms (needle, rod, pin, globular, chromosome shaped), irregular dissemination and possible centrifugal distribution (Figure 4).…”

“…In accordance with the works of Hartong et al8, Okialda et al9 and Ng et al,10 the estimated a prevalence of BCD is 1 in 67,000 individuals, affecting 21,000 patients in China and about 5000 in USA. According to our estimations, the actual prevalence of BCD in Spain may be extremely low, affecting approximately 1 in 4,500,000 subjects, ie, 10–12 cases in the whole country, based on a survey carried out in 2013 in more than 650 medical centers of Spain 11. At the same time, the disease presents worldwide distribution, and tends to be common in the east of Asia, being more prevalent in Chinese, Japanese and Korean populations.…”

“…In the late stages of BCD, severe visual damage and legal blindness are common findings. It should be kept in mind that disease evolution may be asymmetric in the two eyes, that a good visual acuity outcome may not correspond to the measure of damage in the retina and that high variability in disease presentation and evolution has been reported 11,13…”

“…These subclinical alterations course with normal vision and are not essential requirements for BCD diagnosis. They are more commonly described in European than in Asian patients, although the reported frequency of marginal keratopathy is highly variable, ranging from a 75% rate of incidence in Spanish patients11 to the complete absence of keratopathy in a sample of 15 Italian patients 18. The presence of corneal crystalline deposits in the clinical reports and the identified mutations associated with them are summarized in Table 1.…”

Autofluorescence of choroidal vessels in Bietti’s crystalline dystrophy

“… 3 6 However, there is extreme variability in BCD disease presentation. For example, progression may be asymmetric between the two eyes, 7 and individuals with the same CYP4V2 mutation may present differently. 8 9 As such, with its rarity, early asymptomatic stages, painless progression and high variability, BCD can be difficult to diagnose and study.…”