P195 – 2968: Novel mutations of the CDKL5 gene in patients with epileptic encephalopathy

• Published in: European journal of paediatric neurology 2015-05, Vol.19, p.S148-S148
• Main Authors: Kolníková, M, Bognar, C, Foltán, T, Švecová, L, Kádaši, L, Ilenèíková, D, Sýkora, P
• Format: Article
• Language: English
• Subjects: Neurology; Pediatrics
• ISSN: 1090-3798; 1532-2130
• DOI: 10.1016/S1090-3798(15)30508-0

Objective The phenotypic consequences of mutations in gene CDKL5 are: early onset epileptic encephalopathy, severe developmental delay, deceleration of head growth, impaired communication and often hand stereotypies. Epilepsy is typically manifested as an epileptic encephalopathy with infantile spasms (IS) starting between the first and fourth month of life or generalized tonic–clonic seizures, partial complex seizures and myoclonic seizures. We present two children with intractable epilepsy from two months of age (one case predominantly myoclonic and partial complex seizures, the other one with early IS). Methods In both cases, the following investigations were performed: brain MRI, video EEG, available tests for epilepsy caused by a metabolic disorder (blood, urine, cerebrospinal fluid) and molecular mutational analysis of MECP2, CDKL5, FOXG1 genes. Results In the first case (4.5-year old girl) sequence analysis of the CDKL5 gene (reference sequence: ENST0000379996) detected mutation IVS15 + 1G>A in heterozygous state. The revealed mutation has not been published so far. Enans et al. 2005 and Archer et al. 2006 described a similar mutation in intron IVS16 + G>A. The clinical picture of their and our patient with this mutation fulfills Hagberg's criteria for atypical Rett syndrome. In the second case (5.5-year old boy), we detected mutation p.W125X (c.374G>A). This mutation has also not been described in the literature. It is a stop mutation at the beginning of the gene, causing the deletion of 16 exons of the CDKL5 gene, resulting in a non-functional protein due to the catalytic region in the kinase domain. Conclusion Regarding these two presented cases, we point out the importance of molecular analysis, especially of CDKL5 genes as an etiological factor in severe encephalopathy and epilepsy with onset before 6 months of age. In our work we described two novel mutations in CDKL5.