A novel case of Heimler syndrome in a young child with compound heterozygous PEX26 mutations: clinical and genetic insights with literature review

Heimler syndrome is an ultra-rare autosomal recessive disorder belonging to the spectrum of peroxisomal disorders. Heimler syndrome is characterized by sensorineural hearing loss, retinal dystrophy and dental anomalies. It is caused by hypomorphic mutations in peroxisomal biogenesis genes, namely PEX1, PEX6, PEX26, and PEX10. Fewer than 30 cases have been reported to date.We report the case of a male infant born at 36 weeks of gestation with congenital bilateral sensorineural hearing loss, confirmed by abnormal auditory brainstem responses and managed with early bilateral cochlear implantation. Poor visual behavior led to ophthalmologic evaluation, which revealed a "salt-and-pepper" appearance of the peripheral retina and markedly attenuated retinal vessels. Full-field electroretinogram (ffERG) responses were severely reduced and optical coherence tomography revealed abnormal retinal layering. Whole-exome sequencing in trio identified two novel compound heterozygous variants in PEX26.This case broadens the phenotypic and genotypic spectrum of peroxisome biogenesis disorder linked with PEX26, manifesting as Heimler syndrome. The discovery of two novel PEX26 variants contributes to the mutational landscape of peroxisomal biogenesis disorders and underscores the diagnostic value of early ophthalmologic and genetic screening in children with congenital hearing loss.