Case Report: Clinical and genetic analysis of a Bietti crystalline dystrophy family with multisite crystalline deposits and a phenotype of macular hole combined with retinoschisis.

Purpose: To identify and characterize the genetic mutation responsible for Bietti crystalline dystrophy (BCD) in a Chinese consanguineous family and to describe the associated clinical phenotypes. Methods: Comprehensive genetic screening was performed on a Chinese consanguineous family using targeted next-generation sequencing (NGS) of 1,276 ophthalmology-related genes, followed by confirmation with Sanger sequencing. All family members underwent detailed ophthalmologic examinations. Results: We investigated a consanguineous Chinese family affected by Bietti crystalline dystrophy (BCD). The proband, a 46-year-old woman, reported progressive bilateral visual decline and nyctalopia over a span of two decades. Her younger sister exhibited similar symptoms. Ophthalmic examinations revealed crystalline deposits involving the cornea, retina, and lens. Notably, in addition to the previously reported crystal-like deposits on the inner surface of the anterior lens capsule, our cases also demonstrated crystals on the anterior surface of the capsule and within the lens cortex, with the proband showing more extensive involvement than her sister. This novel pattern of anterior capsular surface involvement provides a new perspective on the possible pathways of crystal deposition in BCD. Optical coherence tomography (OCT) revealed cystoid macular edema (CME) in the proband, whereas her sister presented with a rare combination of a full-thickness macular hole (MH) and retinoschisis-an OCT phenotype not previously reported in BCD. Next-generation sequencing (NGS) identified a homozygous splice-site mutation (c.1091-2A > G) in CYP4V2 in the proband, which was confirmed in her sister by Sanger sequencing. Other family members were found to be heterozygous carriers. Genotype-phenotype co-segregation supported the pathogenicity of this variant. Conclusion: The homozygous CYP4V2 c.1091-2A > G mutation was identified as the disease-causing variant in this family. This study broadens the phenotypic spectrum of BCD by highlighting multisite crystalline deposits and rare macular structural changes. These findings suggest that crystal deposition in BCD affects multiple ocular tissues and involves complex pathological mechanisms. Combined multimodal imaging and genetic testing can enhance the recognition and diagnosis of BCD.