Objective To investigate the clinical phenotypes and genetic characteristics of Jalili syndrome. Methods A retrospective clinical study. Four patients diagnosed with Jalili syndrome by genetic testing at Eye Center of Renmin Hospital of Wuhan University from July 2023 to July 2025 were included. The patients were from 4 unrelated families. Detailed medical and family histories were obtained. All patients underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color fundus photography, ultra-widefield fundus autofluorescence imaging, and optical coherence tomography, as well as oral photography. Peripheral venous blood samples were collected from the patients and their family members for genomic DNA extraction. Whole-exome sequencing and bioinformatic analyses were performed. All identified variants were classified according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). ResultsAmong the four patients, there was one male and three females, aged 5, 31 (male), 35, and 40 years. All patients presented with childhood-onset photophobia, nystagmus, and decreased visual acuity, accompanied by dental abnormalities predominantly characterized by amelogenesis imperfecta. The 5-year-old patient exhibited a bull’s-eye maculopathy and mild enamel defects. The 31- and 35-year-old patients showed progressive outer retinal structural damage and visual function decline, along with enamel hypoplasia, discoloration, or dental caries. The 40-year-old patient, from a consanguineous family, developed severe visual impairment in early childhood, accompanied by residual roots, retained primary teeth, and retinal vascular occlusion. Genetic analysis identified six CNNM4 variants highly correlated with the phenotype. Patient 1 carried a nonsense variant c.1555C>T (p.Arg519Ter) (M1) and a missense variant c.1423G>A (p.Val475Met) (M6); patient 2 carried a frameshift variant c.981dup (p.Leu328SerfsTer25) (M2) and a missense variant c.1219C>G (p.Arg407Gly) (M4); patient 3 carried two missense variants c.755T>G (p.Leu252Arg) (M3) and c.452G>T (p.Cys151Phe) (M5); patient 4 carried a homozygous frameshift variant c.981dup (p.Leu328SerfsTer25) (M2). Variants M2, M3, M4, and M5 were novel. According to ACMG guidelines, M1 and M2 were classified as pathogenic, M5 and M6 as likely pathogenic, and M3 and M4 as variants of uncertain significance. ConclusionsJalili syndrome is an early-onset, progressive CNNM4-related oculo-dental syndrome. M2, M3, M4, and M5 are new mutations reported for the first time in this study. The variants M2, M4, and M5 (missense) and M3 (frameshift) are newly identified variants.