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A genetics case report describes a child with long-standing pyridoxine-dependent seizures but no diagnosis on standard exome testing, later showing complex structural changes on deeper genome analysis.
Most families who hear “PDE” learn about ALDH7A1 (and a small set of related vitamin B6 pathway genes). But some patients have a PDE-like clinical picture without clear answers from first-line genetic tests. This can be deeply frustrating, especially when the clinical response to pyridoxine is strong.
In this paper, the authors describe a child whose seizures recurred when pyridoxine was stopped and resolved when it was restarted, despite an unremarkable whole-exome sequencing result. They then used optical genome mapping and whole-genome sequencing, finding a recurrent 16p11.2 duplication and a de novo, chromothripsis-type unbalanced translocation involving multiple genes. The authors argue that genome structural complexity (and how it can reshape gene regulation in 3D) might create unusual vulnerabilities in pathways tied to pyridoxine dependence, and they call for broader genetic approaches in select unexplained cases.
Why this matters
For some families, “negative” early genetic testing may not be the end of the road. This report highlights newer tools that can detect structural variants and complex rearrangements that exome sequencing can miss.
Limitations
This is a single case report, and the authors do not identify one definitive causal gene. The findings are hypothesis-generating and mainly support the idea of broader testing when the phenotype is compelling.
Sources
- Falsaperla R et al. “Chromothriptic Translocation t(1;18): A Paradigm of Genomic Complexity in a Child with Normal Intellectual Development and Pyridoxine-Dependent Epilepsy.” Genes (2025). DOI: 10.3390/genes16111334 (PubMed: 41300786; Free full text: PMC12652939)
Safety note: This summary is educational and not medical advice.
