RESUMEN
The diagnosis of early infantile epileptic encephalopathy (EIEE) remains challenging, and next-generation sequencing (NGS) techniques have played a key role in identifying genetic causes. Recent studies have shown an association between mutations in the CYFIP2 gene and EIEE, with 20 deleterious variants reported so far and a de novo mutational hotspot at codon 87. A male infant presented with seizures since the age of four months as well as significant developmental delay and microcephaly. The seizures were of different types, frequent and refractory to treatment, including different anticonvulsant drugs. Metabolic studies showed no significant changes. The initial electroencephalogram revealed bilateral paroxysmal activity with hemispherical diffusion. Brain MRI showed no pathological changes. Analysis of a whole exome sequencing (WES) based multigene panel for epilepsy disclosed a heterozygous CYFIP2 gene variant [c.258_266del; p.(Trp86_Ser88del)] established as de novo. We describe the case of an infant with EIEE due to a de novo heterozygous in-frame deletion of three amino acids in CYFIP2: c.258_266del; p.(Trp86_Ser88del). This in-frame deletion eliminates codon 87, a mutational hotspot associated with a particularly severe EIEE phenotype. All previous reports had missense variants with a presumably gain-of-function mechanism. The clinical picture of our patient is very similar to the ones with deleterious variants affecting codon 87 reported in the literature. Our case report is the first to describe a disease-causing in-frame deletion in CYFIP2 and reiterates a consistent genotype-phenotype correlation.