Distinct Phenotypes of Primary Ciliary Dyskinesia in Monozygotic Twins with Defective HYDIN Gene: a Case Report

Primary ciliary dyskinesia (PCD) is an autosomal recessive, genetically and phenotypically heterogeneous disorder characterized by impaired mucociliary clearance and recurrent respiratory infections. Although genotype–phenotype correlations are well established in PCD, intrafamilial phenotypic variability remains poorly understood. Here, we report monozygotic twins with biallelic variants in the HYDIN gene who exhibit markedly discordant clinical severity and ciliary function despite an identical genetic background. Transmission electron microscopy, high-speed video microscopy, immunofluorescence, and electron tomography were used to asses ciliary structure and function. Both patients were diagnosed with PCD with normal ciliary ultrastructure. Transmission electron microscopy revealed a significantly higher proportion of secondary ciliary ultrastructural defects in patient 1, who also demonstrated a higher clinical index and distinct ciliary beating patterns on high-speed video microscopy compared with patient 2. Genetic findings were confirmed by immunofluorescence and electron tomography in both patients. Despite sharing the same pathogenic HYDIN variants, patient 1 exhibited a significantly higher frequency of numerical axonemal defects, correlating with altered ciliary motility and more severe clinical manifestations. Monozygotic individuals with identical pathogenic HYDIN variants may show discordant clinical severity and ciliary function, highlighting intrafamiliar phenotypic variability in PCD.