Key result
Novel KCNQ2 variants expand the phenotypic spectrum to epilepsy with auditory features without neonatal seizures.
Why the study?
Pathogenic KCNQ2 variants are associated with a wide phenotypic spectrum of neonatal epilepsies, but variability beyond typical neonatal seizures is not fully characterized.
Observational (n=12)
No
The study expands the phenotypic spectrum of KCNQ2-related epilepsies to include epilepsy with auditory features, suggesting KCNQ2 should be included in screening panels for this condition.
May support KCNQ2 screening in epilepsy with auditory features; hypothesis-generating and requires validation in larger cohorts.
Pathogenic KCNQ2 variants are associated with neonatal epilepsies, ranging from self-limited neonatal epilepsy to KCNQ2–developmental and epileptic encephalopathy (DEE). In this study, next-generation sequencing was performed, applying a panel of 142 epilepsy genes on three unrelated individuals and affected family members, showing a wide variability in the epileptic spectrum. The genetic analysis revealed two likely pathogenic missense variants (c.1378G>A and c.2251T>G) and the already-reported pathogenic splice site (c.1631+1G>A) in KCNQ2 (HGNC:6296). The phenotypes observed in the affected members of family 1, which shared the c.2251T>G variant, were epilepsy with auditory features (EAFs), focal epilepsy, and generalized epilepsy, and none of them suffered from neonatal seizures. The gene panel contained further genes related to EAFs (LGI1, RELN, SCN1A, and DEPDC5), which were tested with negative results. The phenotypes observed in family 2 members, sharing the splice site variant, were neonatal seizures and focal epilepsy in childhood. The last unrelated proband, harboring the de novo missense c.1378G>A, presented a clinical phenotype consistent with DEE. In conclusion, we identified two unreported KCNQ2 variants, and report a proband with EAFs and individuals without typical KCNQ2 neonatal seizures. Our study underscores the extreme variability in the phenotypic spectrum of KCNQ2-related epilepsies and unveils the prospect of its inclusion in screening panels for EAFs.
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Talarico et al. (2024) conducted an observational in Epilepsy (KCNQ2-related epilepsies) (n=12). KCNQ2 variants vs. Unaffected family members and healthy controls was evaluated. Two novel KCNQ2 variants (c.1378G>A and c.2251T>G) and one known pathogenic splice site variant were identified, expanding the phenotypic spectrum of KCNQ2-related disorders to include epilepsy with auditory features without neonatal seizures.
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