Heimler Syndrome With Tooth Agenesis, Abnormal Enamel and Dentin Mineralization, Root Maldevelopment, and PEX1 Mutation

Abstract

Biallelic variants in the PEX1 and PEX6 genes are implicated in Heimler syndrome, which is characterized by amelogenesis imperfecta, sensorineural hearing loss, retinitis pigmentosa, and nail defects. The objective of this study is to find the genetic variant and to analyze the teeth of a patient with Heimler syndrome. Clinical and radiographic examination and whole exome sequencing were performed on a Heimler syndrome patient and his parents. Scanning electron microscopy and micro-computed tomography were performed on a tooth. Immunohistochemical study of Pex1 was performed. Mutant protein models were made. The authors report an 18-year-old male with Heimler syndrome who carried a compound heterozygous (c.2966T>C; p.Ile989Thr and c.2097_2098insT; p.Ile700TyrfsTer42) mutation in the PEX1 gene. Clinical manifestations included amelogenesis imperfecta of the posterior permanent teeth, mild sensorineural hearing loss, retinitis pigmentosa, and leukonychia. SEM showed enamel and dentin dysmineralization. The newly findings include arachnodactyly, tooth agenesis, microdontia, root maldevelopment, and failure of tooth eruption. The p.Ile700TyrfsTer42 variant is predicted to produce a non-viable protein. The p.Ile989Thr variant is predicted to disrupt its interaction with PEX6. A patient with Heimler syndrome may have arachnodactyly, tooth agenesis, microdontia, delayed dental development, root maldevelopment, enamel and dentin dysmineralization, and failure of tooth eruption. © 2025 The Authors