Heimler Syndrome: A Report of 2 Indian Children With Review of Literature

Introduction Heimler syndrome 1 is a group of peroxisomal biogenesis disorders due to the pathogenic variations in the peroxisomal biogenesis factor 1 ( PEX1 ) gene resulting in the dysfunction of intracellular peroxisomes. PEX1 gene encodes proteins that are involved in the import of peroxisomal matrix proteins. Patients A 6-year-old boy, second born to nonconsanguineous parents, presented with global developmental delay, progressive hearing loss, and night blindness. He had an uneventful antenatal and perinatal period. He had a significant family history with similar complaints of global developmental delay and progressive hearing loss in a 3-year-old younger sibling. Results Ophthalmologic evaluation of both siblings revealed bilateral retinitis pigmentosa. Brainstem evoked response audiometry was suggestive of bilateral sensorineural hearing loss. Brain magnetic resonance imaging (MRI) of the index child revealed T2-weighted and fluid-attenuated inversion recovery hyperintensity involving the splenium of the corpus callosum, bilateral periatrial white matter without diffusion restriction. Whole exome sequencing revealed a heterozygous 5′ splice site variant in intron-21 affecting donor splice site of exon-21 (c.3438+2T>C), and a heterozygous missense variant in exon-5 (p.Thr173Asn) of the PEX1 gene. Conclusion We report 2 cases of Heimler syndrome 1 with novel neuroimaging features with a review of the literature available on this very rare entity. Heimler syndrome 1 is a rare peroxisomal biogenesis disorder presenting with bilateral sensorineural hearing loss, retinitis pigmentosa, teeth, and nail changes. Children presenting with similar phenotypes should be genetically tested for pathogenic variations of PEX1 and PEX6 genes, as there are currently no biochemical signatures available for diagnosing Heimler syndrome and significant clinical overlap with other syndromes.