Compound heterozygous variants in CYP4V2 and LRTOMT coinciding in a single family: a rare case of combined Bietti crystalline dystrophy and nonsyndromic hearing loss

This study reports the rare co-occurrence of CYP4V2 (causing Bietti crystalline dystrophy, BCD) and LRTOMT (causing nonsyndromic hearing loss) variants within a single family and analyzes their clinical correlation. Exome sequencing was performed on three siblings with distinct clinical phenotypes. Sanger sequencing was used for variant confirmation. Although parental data was unavailable, the inheritance pattern was analyzed through co-segregation within the family. The proband, affected by both conditions, carried compound heterozygous variants in both CYP4V2 and LRTOMT genes. This correlated with more severe hearing loss compared to siblings carrying only LRTOMT variants. Siblings with isolated BCD or hearing loss carried variants only in the respective single gene. The findings suggest a double-compound heterozygous state in the proband. This case highlights the genetic complexity of multisensory disorders, where the co-inheritance of variants in distinct genes may lead to a more severe phenotype. It underscores the need for comprehensive genetic testing and counseling in affected families.