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Purpose: The aim of this study was to investigate the molecular basis of childhood glaucoma in Switzerland to recommend future targeted genetic analysis in the Swiss population., Methods: Whole-exome sequencing and copy number variation (CNV) analysis was performed in a Swiss cohort of 18 patients from 14 unrelated families. Identified variants were validated by Sanger sequencing and multiplex ligation-dependent probe amplification. Breakpoints of structural variants were determined by a microarray. A minigene assay was conducted for functional analysis of a splice site variant., Results: A diagnosis of primary congenital glaucoma was made in 14 patients, of which six (43%) harbored pathogenic variants in CYP1B1 , one (7%) a frameshift variant in FOXC1 , and seven (50%) remained without a genetic diagnosis. Three patients were diagnosed with glaucoma associated with nonacquired ocular anomalies, of which two patients with mild ocular features of Axenfeld-Rieger syndrome harbored a FOXC1 duplication plus an additional FOXC1 missense variant, and one patient with a Barkan membrane remained without genetic diagnosis. A diagnosis of juvenile open-angle glaucoma was made in one patient, and genetic analysis revealed a FOXC1 duplication., Conclusions: Sequencing of CYP1B1 and FOXC1 , as well as analysis of CNVs in FOXC1 , should be performed before extended gene panel sequencing., Translational Relevance: The identification of the molecular cause of childhood glaucoma is a prerequisite for genetic counseling and personalized care for patients and families., Competing Interests: Disclosure: E. Lang, None; S. Koller, None; L. Bähr, None; M. Töteberg-Harms, None; D. Atac, None; F. Roulez, None; A. Bahr, None; K. Steindl, None; S. Feil, None; W. Berger, None; C. Gerth-Kahlert, None, (Copyright 2020 The Authors.)