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Novel Co-Occurrence of Slc26a4 and Kctd7 Variants in a Pediatric Patient With Syndromic Hearing Loss and Myoclonic Epilepsy Publisher



F Shariatmadari FAKHREDDIN ; Amm Kamal Amir Mahdi MOHAMADI ; A Mobini ARSHIA ; S Bayat SHIVA ; Z Rezaei ZAHRA ; Rs Badv Reza SHERVIN ; M Mohammadi MAHMOUD ; H Yousefimanesh HOSSEIN
Authors

Source: Egyptian Journal of Medical Human Genetics Published:2025


Abstract

Background: Syndromic hearing loss and progressive myoclonic epilepsy are distinct genetic disorders with well-established genes implicated. SLC26A4 is commonly associated with hearing loss, including Pendred syndrome, while KCTD7 is linked to PME, characterized by intractable seizures, cognitive regression, and ataxia. The co-occurrence of these two conditions in a single patient has not been previously reported. Case presentation: We describe a 2-year-old boy presenting with bilateral severe-to-profound hearing loss, progressive myoclonic epilepsy, and global developmental delay. Whole exome sequencing revealed homozygous pathogenic and uncertain variants in SLC26A4 (c.1337A > G, p.Gln446Arg) and KCTD7 (c.766G > A, p.Gly256Ser), respectively. This is the first reported case of a patient with dual pathogenic and VUS variants in these genes, presenting with a novel combined phenotype. The patient showed partial seizure control with a regimen of clobazam, levetiracetam, and ACTH therapy. Notably, his auditory responses improved following seizure management, suggesting a possible interaction between epilepsy and auditory function. Conclusion: This case highlights the importance of comprehensive genetic evaluation in patients with overlapping neurodevelopmental disorders. The co-occurrence of SLC26A4 and KCTD7 variants suggests a potential novel phenotype requiring further investigation. Functional studies and long-term follow-up are needed to assess the pathogenicity of the KCTD7 variant and its clinical significance in progressive myoclonic epilepsy. © 2025 Elsevier B.V., All rights reserved.
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