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Literature suggests corneal morphologic characteristics compatible with keratoconus are present in a high percentage of patients with Down syndrome (DS), suggesting the need to perform a detailed examination of the anterior segment to try to avoid serious visual impairment in this group of patients.To characterize the abnormal features of the cornea in patients with DS and compare these with a control group.Multicenter case-control study at Vissum Alicante, Alicante, Spain, and the Ophthalmology and Pediatric Department, Cairo University, Cairo, Egypt. Data collection took place between May 2013 and May 2016. Data were analyzed between June 2016 and August 2016. The study included 321 eyes of 217 participants from 2 groups: 112 participants in the DS group and 105 healthy participants in the control group.Patients were evaluated using Placido disc/Scheimpflug camera topographer (Sirius, CSO). Visual, refractive and anterior, and posterior corneal characteristics were assessed and compared in both groups.Keratoconus diagnosis. Incidence of corneal morphologic irregularities similar to keratoconus in patients with DS.In the DS group, mean (SD) age was 14.88 (15.76) years, 54 (48%) were women, 66 (59%) were white, and 46 (41%) were Arab. In the control group, mean (SD) age was 40.29 (14.66) years, 54 (51%) were women, and all were white. Clinical assessment of corneal topography showed that 71.3% (95% CI, 45.2-97.4) of patients in the DS group showed characteristics compatible with keratoconus. Differences were found in steepest keratometry of 47.35 diopters (D) in patients with DS vs 43.70 D in control individuals (difference, 3.65 D; 95% CI, 3.23-4.35 D; P <.001) and in corneal pachymetry of 503 μm in patients with DS vs 545 μm in control individuals (difference, 42 μm; 95% CI, 38.8-56.7 μm; P <.001).Patients with DS have steeper and thinner corneas and more corneal aberrations than those without genetic alterations and normal corneas. The findings suggest a detailed corneal study should be considered in such patients to detect keratoconus and implement treatment as appropriate to try to avoid serious visual impairment in this group of patients.