BACKGROUND: Epilepsy with intellectual disability limited to females (Epileptic encephalopathy, early infantile, 9; EIEE9) is a rare early infantile epileptic encephalopathy characterized by an unusual X-linked inheritance: females with heterozygous mutations are affected, while hemizygous males are not. CASE PRESENTATION: We describe the clinical and molecular characteristics of 2 Russian patients with EIEE9 (females, ages 3 years and 7 years). In these patients seizures developed at the age of 3 years. Additionally, for our patients and for cases described in the literature we searched for a possible relationship between the type and localization of the mutation and the EIEE9 clinical phenotype. CONCLUSIONS: We identified two novel PCDH19 mutations in EIEE9 patients: a missense mutation in exon 1 (c.1236C > A, p.Asp412Glu) and a frameshift in exon 3 (c.2386_2387insGTCT, p.Thr796fs). We conclude that the age of seizure onset and the presence of intellectual disability may depend not on the type and localization of PCDH19 mutations, but on the X-inactivation status. The study also highlights the need to screen for EIEE9 among young female epilepsy patients.
Cadherins/genetics , Epilepsy/genetics , Frameshift Mutation , Genetic Diseases, X-Linked/genetics , Intellectual Disability/genetics , Mutation, Missense , Age of Onset , Cadherins/deficiency , Child , Child, Preschool , Epilepsy/diagnosis , Epilepsy/pathology , Female , Gene Expression , Genes, X-Linked , Genetic Diseases, X-Linked/diagnosis , Genetic Diseases, X-Linked/pathology , Heterozygote , Humans , Intellectual Disability/diagnosis , Intellectual Disability/pathology , Pedigree , Protocadherins , Exome Sequencing , X Chromosome Inactivation
