KCNQ3 – Benign familial infantile epilepsy

Benign familial infantile epilepsy (BFIE) is characterized by focal seizures in the first year of life and follows an autosomal dominant inheritance pattern with incomplete penetrance. Although PRRT2 mutations account for the majority of BFIE cases, heterozygous KCNQ3 missense variants have now been reported in five unrelated individuals, including a novel KCNQ3 c.1850G>C (p.Ser617Thr) variant inherited from an unaffected parent, suggesting reduced penetrance (5 probands) (PMID:33337327).

Segregation analysis is limited: the p.Ser617Thr variant was found in an asymptomatic father with no additional affected relatives. Functional studies of wild-type KCNQ3 show that it co-assembles with KCNQ2 to form M-type potassium currents in Xenopus oocytes and is co-expressed in the hippocampus, neocortex, and cerebellum (PMID:10788442; PMID:9827540). No BFIE-specific functional assays of KCNQ3 variants have been reported. The limited number of reported probands, lack of robust segregation, and absence of variant-specific functional data currently constrain clinical validity. Further genetic and electrophysiological studies are required to confirm the role of KCNQ3 in BFIE and guide diagnostic testing.

Key Take-home: KCNQ3 variants are a rare cause of BFIE with incomplete penetrance; additional evidence is needed before routine clinical implementation.

References

• Epileptic disorders : international epilepsy journal with videotape • 2020 • Benign familial infantile epilepsy associated with KCNQ3 mutation: a rare occurrence or an underestimated event? PMID:33337327
• The Journal of biological chemistry • 2000 • Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. PMID:10788442
• FEBS letters • 1998 • The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. PMID:9827540

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