TBC1D24 – Malignant migrating partial seizures of infancy

Malignant migrating partial seizures of infancy (MMPSI) is a devastating early‐onset epileptic encephalopathy characterized by pharmacoresistant focal seizures and migratory EEG discharges. In a consanguineous family, two siblings presented with MMPSI due to compound heterozygous truncating mutations in TBC1D24: c.132G>A (p.Trp44Ter) and c.270_286del (p.Pro91fs), segregating in an autosomal recessive pattern (PMID:23526554). No additional pathogenic variants were found in eight other MMPSI cases screened in the same study.

Functional studies demonstrated that these mutations severely impaired TBC1D24 expression and disrupted maturation of neuronal circuits in patient‐derived cells (PMID:23526554). A subsequent targeted resequencing of six unrelated MMPSI patients failed to identify TBC1D24 pathogenic mutations, highlighting locus heterogeneity in MMPSI (PMID:24315024). Given evidence from a single family (two probands) with segregation and in vitro functional data, the gene–disease relationship is classified as Limited. Nevertheless, TBC1D24 testing should be considered in familial MMPSI for diagnostic confirmation and genetic counseling.

References

• Human mutation • 2013 • Novel compound heterozygous mutations in TBC1D24 cause familial malignant migrating partial seizures of infancy. PMID:23526554
• Epilepsy research • 2014 • Lack of pathogenic mutations in six patients with MMPSI. PMID:24315024

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