Background and Aim: Hyper-Immunoglobulin M (IgM) syndrome (HIGM) is a rare primary immunodeficiency in which defective B-cell isotype switching results in a phenotype characterized by elevated or normal serum IgM levels and low levels of other Ig classes, leading to an increased susceptibility to infection, neutropenia, autoimmune disorders, and malignancies. In this disease, a mutation occurs in the CD40 gene, leading to combined B-cell and T-cell immunodeficiencies. The oral manifestations include wound-like lesions, oral candidiasis, gingivitis, periodontitis, and enamel defects. Theoretically, systemic conditions affecting ameloblastic activity during enamel mineralization, such as abnormal oxygen levels resulting from hypoventilation in various respiratory diseases, result in enamel defects. Case presentation: We report a 10-year-old male with hyper-IgM immunodeficiency. The patient had suffered from frequent infections, respiratory problems, and bronchopneumonia from the age of 2 years. At 4 years of age, type 1 diabetes mellitus was diagnosed. During dental examinations, enamel defects were found in seven permanent teeth. Conclusion: A meticulous dental evaluation of children with systemic diseases is mandatory in order to discover possible developmental dental defects and to plan early interventions.