Navigating the complexities of dual CNV findings: a case of DEE7 caused by a de novo KCNQ2 deletion and a Co-occurring chromosome 13 duplication – a case report and literature review

BackgroundDevelopmental and epileptic encephalopathy 7 (DEE7) is a severe neurodevelopmental disorder stemming from mutations in the KCNQ2 gene, which encodes a critical voltage-gated potassium channel subunit. While KCNQ2 mutations are known to cause a spectrum of diseases, from benign familial neonatal seizures (BFNS1) to drug-resistant DEE7, the clinical outcomes specifically associated with large deletions—a rare mechanism causing haploinsufficiency—are not well defined. This study reports a de novo KCNQ2 large deletion and aims to delineate the associated clinical trajectory and treatment response.Case summaryWe report a 1 year 5 months female who presented with frequent seizures starting in the neonatal period (7 days after birth), characterized by limb stiffness and facial cyanosis, with a frequency of 4–5 episodes per week. Initial neurological examination revealed no focal deficits, and brain MRI showed no structural abnormalities. However, electroencephalography demonstrated slowed background activity with multifocal epileptiform discharges. Standardized neurodevelopmental assessments confirmed severe global delay (Griffiths Developmental Quotient of 60 and Alberta Infant Motor Scale score below the 5th percentile at 3 months of age). Trio-based whole-exome sequencing was performed, identifying a ∼1.62 Mb de novo heterozygous deletion at chromosome 20q13.33 and a co-occurring ∼4.68 Mb duplication at chromosome 13q34 in the proband. This variant was classified as pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines and fully encompassed the KCNQ2 gene, leading to a definitive diagnosis of KCNQ2-related developmental and epileptic encephalopathy 7 (DEE7).ConclusionWe diagnosed DEE7 caused by a large KCNQ2 deletion using trio whole-exome sequencing and multiplex ligation-dependent probe amplification (MLPA). Despite the severe genotype, early targeted treatment led to complete seizure freedom and modest neurodevelopmental progress. This case demonstrates that seizure freedom and some developmental gains are achievable, highlighting the potential benefit of early intervention even in patients with severe genotypes and underscoring the need for copy number variation (CNV) analysis in epilepsy genetic testing.